Ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate Prevents Progression of Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

Therapies to prevent onset and progression of pulmonary arterial pressure are not very effective yet. This study was designed to investigate the effects of a novel dihydropyrimidinone, ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate (H-DHPM) on pathogenesis of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). For the same purpose, rats were injected intraperitoneally (i.p.) a single dose (60 mg/kg) of MCT which led to development of PAH in 21 days. MCT insult caused high mortality, pulmonary vascular and parenchymal remodelling. Since the course of PAH pathogenesis is characterised by an early onset and progression phases, H-DHPM was administered i.p. at 30 mg/kg dosage in MCT pre-injected animals either from day 0 through day 21 or day 14 though day 21 of MCT injection in two separate treatment groups. H-DHPM significantly improved survival, prevented remodelling of pulmonary vasculature and parenchyma and subsequently ameliorated PAH pathogenesis. Moreover, we observed significant decrease in right ventricle hypertrophy, measured by wet weight of right ventricle (RV) divided by wet weight of left ventricle plus septum (LV+S), in H-DHPM treated groups as compared to MCT injected animals. These findings suggest H-DHPM not only prevented development of PAH but also treated the PAH pathogenesis in progressive phase. In conclusion, our data determines H-DHPM, might be a future drug for the prevention of PAH

Revisiting the role of CP-conserving processes in cosmological particle-antiparticle asymmetries

We point out qualitatively different possibilities on the role of CP-conserving processes in generating cosmological particle-antiparticle asymmetries, with illustrative examples from models in leptogenesis and asymmetric dark matter production. In particular, we consider scenarios in which the CP-violating and CP-conserving processes are either both decays or both scatterings, thereby being naturally of comparable rates. This is in contrast to the previously considered CP-conserving processes in models of leptogenesis in different see-saw mechanisms, in which the CP-conserving scatterings typically have lower rates compared to the CP-violating decays, due to a Boltzmann suppression. We further point out that the CP-conserving processes can play a dual role if the asymmetry is generated in the mother sector itself, in contrast to the conventional scenarios in which it is generated in the daughter sector. This is because, the CP-conserving processes initially suppress the asymmetry generation by controlling the out-of-equilibrium number densities of the bath particles, but subsequently modify the ratio of particle anti-particle yields at the present epoch by eliminating the symmetric component of the bath particles through pair-annihilations, leading to a competing effect stemming from the same process at different epochs. We find that the asymmetric yields for relevant particle-antiparticle systems can vary by orders of magnitude depending upon the relative size of the CP-conserving and violating reaction rates.Comment: 12 pages, 6 figures; v2: 15 pages, substantially rewritten text, new figures, version to appear in European Physical Journal

Screening of cyanobacterial strains for UV screening compound Scytonemin - Environmental Perspectives

Abstract: Cyanobacteria has evolved the capacity to synthesize, mount up and metabolize scytonemin a photoprotective pigment as a part of an overall tactic to taper the unswerving and oblique destructive effects of environmental ultraviolet radiation (UVR) due to the deterioration of ozone layer attributable to the release of pollution containing the chemicals chlorine and bromine. Scytonemin is an indole phenolic pigment found in the sheath of many cyanobacteria having a unique dimeric structure, ecological importance and novel pharmaceutical activity have enthused substantial pursuit in its biosynthesis. This study includes the screening of scytonemin from 46 studied cyanobacterial strains out of which 23 showed the presence of scytonemin. Aulosira fertilissima showed the maximum scytonemin. The effect of environmental factors, including Light intensity, photoperiod, UV-light was studied on scytonemin synthesis of A. fertilissima. A remarkable change in scytonemin synthesis was observed under UV-light stress. Scytonemin increased under all stress conditions but it increased maximally under UV-light stress

Caffeine and Modafinil Ameliorate the Neuroinflammation and Anxious Behavior in Rats during Sleep Deprivation by Inhibiting the Microglia Activation

Background: Sleep deprivation (SD) plagues modern society due to the professional demands. It prevails in patients with mood and neuroinflammatory disorders. Although growing evidence suggests the improvement in the cognitive performance by psychostimulants during sleep-deprived conditions, the impending involved mechanism is rarely studied. Thus, we hypothesized that mood and inflammatory changes might be due to the glial cells activation induced modulation of the inflammatory cytokines during SD, which could be improved by administering psychostimulants. The present study evaluated the role of caffeine/modafinil on SD-induced behavioral and inflammatory consequences.Methods: Adult male Sprague-Dawley rats were sleep deprived for 48 h using automated SD apparatus. Caffeine (60 mg/kg/day) or modafinil (100 mg/kg/day) were administered orally to rats once every day during SD. Rats were subjected to anxious and depressive behavioral evaluation after SD. Subsequently, blood and brain were collected for biochemical, immunohistochemical and molecular studies.Results: Sleep deprived rats presented an increased number of entries and time spent in closed arms in elevated plus maze test and decreased total distance traveled in the open field (OF) test. Caffeine/modafinil treatment significantly improved these anxious consequences. However, we did not observe substantial changes in immobility and anhedonia in sleep-deprived rats. Caffeine/modafinil significantly down-regulated the pro- and up-regulated the anti-inflammatory cytokine mRNA and protein expression in the hippocampus during SD. Similar outcomes were observed in blood plasma cytokine levels. Caffeine/modafinil treatment significantly decreased the microglial immunoreactivity in DG, CA1 and CA3 regions of the hippocampus during SD, however, no significant increase in immunoreactivity of astrocytes was observed. Sholl analysis signified the improvement in the morphological alterations of astrocytes and microglia after caffeine/modafinil administration during SD. Stereological analysis demonstrated a significant improvement in the number of ionized calcium binding adapter molecule I (Iba-1) positive cells (different states) in different regions of the hippocampus after caffeine or modafinil treatment during SD without showing any significant change in total microglial cell number. Eventually, the correlation analysis displayed a positive relationship between anxiety, pro-inflammatory cytokines and activated microglial cell count during SD.Conclusion: The present study suggests the role of caffeine or modafinil in the amelioration of SD-induced inflammatory response and anxious behavior in rats.Highlights- SD induced mood alterations in rats.- Glial cells activated in association with the changes in the inflammatory cytokines.- Caffeine or modafinil improved the mood and restored inflammatory changes during SD.- SD-induced anxious behavior correlated with the inflammatory consequences

Image_1.tif

<p>Background: Sleep deprivation (SD) plagues modern society due to the professional demands. It prevails in patients with mood and neuroinflammatory disorders. Although growing evidence suggests the improvement in the cognitive performance by psychostimulants during sleep-deprived conditions, the impending involved mechanism is rarely studied. Thus, we hypothesized that mood and inflammatory changes might be due to the glial cells activation induced modulation of the inflammatory cytokines during SD, which could be improved by administering psychostimulants. The present study evaluated the role of caffeine/modafinil on SD-induced behavioral and inflammatory consequences.</p><p>Methods: Adult male Sprague-Dawley rats were sleep deprived for 48 h using automated SD apparatus. Caffeine (60 mg/kg/day) or modafinil (100 mg/kg/day) were administered orally to rats once every day during SD. Rats were subjected to anxious and depressive behavioral evaluation after SD. Subsequently, blood and brain were collected for biochemical, immunohistochemical and molecular studies.</p><p>Results: Sleep deprived rats presented an increased number of entries and time spent in closed arms in elevated plus maze test and decreased total distance traveled in the open field (OF) test. Caffeine/modafinil treatment significantly improved these anxious consequences. However, we did not observe substantial changes in immobility and anhedonia in sleep-deprived rats. Caffeine/modafinil significantly down-regulated the pro- and up-regulated the anti-inflammatory cytokine mRNA and protein expression in the hippocampus during SD. Similar outcomes were observed in blood plasma cytokine levels. Caffeine/modafinil treatment significantly decreased the microglial immunoreactivity in DG, CA1 and CA3 regions of the hippocampus during SD, however, no significant increase in immunoreactivity of astrocytes was observed. Sholl analysis signified the improvement in the morphological alterations of astrocytes and microglia after caffeine/modafinil administration during SD. Stereological analysis demonstrated a significant improvement in the number of ionized calcium binding adapter molecule I (Iba-1) positive cells (different states) in different regions of the hippocampus after caffeine or modafinil treatment during SD without showing any significant change in total microglial cell number. Eventually, the correlation analysis displayed a positive relationship between anxiety, pro-inflammatory cytokines and activated microglial cell count during SD.</p><p>Conclusion: The present study suggests the role of caffeine or modafinil in the amelioration of SD-induced inflammatory response and anxious behavior in rats.</p><p>Highlights</p><p>- SD induced mood alterations in rats.</p><p>- Glial cells activated in association with the changes in the inflammatory cytokines.</p><p>- Caffeine or modafinil improved the mood and restored inflammatory changes during SD.</p><p>- SD-induced anxious behavior correlated with the inflammatory consequences.</p

Open data from the first and second observing runs of Advanced LIGO and Advanced Virgo

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software