248 research outputs found
Switching the Spin State of Pentafluorophenylnitrene: Isolation of a Singlet Arylnitrene Complex
The
chemistry of arylnitrenes is dominated by their triplet ground
states and excited open-shell singlet states. This results in radical-type
reactions and unwanted rearrangements, which diminish the use of arylnitrenes
as intermediates in organic synthesis. While the closed-shell singlet
states of arylnitrenes are expected to undergo useful chemical transformations
(comparable to the closed-shell singlet states of carbenes), these
states are too high in energy to be chemically accessible. When triplet
pentafluorophenylnitrene is interacting with the Lewis acid BF<sub>3</sub> under the conditions of matrix isolation, a Lewis acid–base
complex consisting of the closed-shell singlet state of the nitrene
and two molecules of BF<sub>3</sub> is formed. Although the closed-shell
singlet state of pentafluorophenylnitrene is calculated (CCSDÂ(T))
to lie more than 25 kcal/mol above its triplet ground state, the reaction
with BF<sub>3</sub> results in switching the spin state from triplet
to singlet. The formation of the singlet complex was monitored by
IR, UV–vis, and EPR spectroscopy. DFT, CCSDÂ(T), and CASPT2
calculations confirm the experimental findings
The 9-O-acetyl GD3 gangliosides are expressed by migrating chains of subventricular zone neurons in vitro
Subacute AMD3100 treatment is not efficient in neonatal hypoxic-schemic rats
Background and Purpose:
Despite the advances in treating neonatal hypoxic-ischemic encephalopathy (HIE) with induced hypothermia, the rates of severe disability are still high among survivors. Preclinical studies have indicated that cell therapies with hematopoietic stem/progenitor cells could improve neurological outcomes in HIE. In this study, we investigated whether the administration of AMD3100, a CXCR4 antagonist that mobilizes hematopoietic stem/progenitor cells into the circulation, has therapeutic effects in HIE.
Methods:
P10 Wistar rats of both sexes were subjected to right common carotid artery occlusion or sham procedure, and then were exposed to hypoxia for 120 minutes. Two subcutaneous injections of AMD3100 or vehicle were given on the third and fourth day after HIE. We first assessed the interindividual variability in brain atrophy after experimental HIE and vehicle treatment in a small cohort of rats. Based on this exploratory analysis, we designed and conducted an experiment to test the efficacy of AMD3100. Brain atrophy on day 21 after HIE was defined as the primary end point. Secondary efficacy end points were cognitive (T-water maze) and motor function (rotarod) on days 17 and 18 after HIE, respectively.
Results:
AMD3100 did not decrease the brain atrophy in animals of either sex. Cognitive impairments were not observed in the T-water maze, but male hypoxic-ischemic animals exhibited motor coordination deficits on the rotarod, which were not improved by AMD3100. A separate analysis combining data from animals of both sexes also revealed no evidence of the effectiveness of AMD3100 treatment.
Conclusions:
These results indicate that the subacute treatment with AMD3100 does not improve structural and functional outcomes in a rat HIE model
Structure-Based Design and Optimization of Multitarget-Directed 2H-Chromen-2-one Derivatives as Potent Inhibitors of Monoamine Oxidase B and Cholinesterases
The multifactorial nature of Alzheimer’s disease calls for the development of multitarget agents addressing key pathogenic processes. To this end, by following a docking-assisted hybridization strategy, a number of aminocoumarins were designed, prepared, and tested as monoamine oxidases (MAOs) and acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitors. Highly flexible N-benzyl-N-alkyloxy coumarins 2–12 showed good inhibitory activities at MAO-B, AChE, and BChE but low selectivity. More rigid inhibitors, bearing meta- and para-xylyl linkers, displayed good inhibitory activities and high MAO-B selectivity. Compounds 21, 24, 37, and 39, the last two featuring an improved hydrophilic/lipophilic balance, exhibited excellent activity profiles with nanomolar inhibitory potency toward hMAO-B, high hMAO-B over hMAO-A selectivity and submicromolar potency at hAChE. Cell-based assays of BBB permeation, neurotoxicity, and neuroprotection supported the potential of compound 37 as a BBB-permeant neuroprotective agent against H2O2-induced oxidative stress with poor interaction as P-gp substrate and very low cytotoxicity
Analyses of zebrafish and Xenopus oocyte maturation reveal conserved and diverged features of translational regulation of maternal cyclin B1 mRNA
<p>Abstract</p> <p>Background</p> <p>Vertebrate development relies on the regulated translation of stored maternal mRNAs, but how these regulatory mechanisms may have evolved to control translational efficiency of individual mRNAs is poorly understood. We compared the translational regulation and polyadenylation of the cyclin B1 mRNA during zebrafish and <it>Xenopus </it>oocyte maturation. Polyadenylation and translational activation of cyclin B1 mRNA is well characterized during <it>Xenopus </it>oocyte maturation. Specifically, <it>Xenopus </it>cyclin B1 mRNA is polyadenylated and translationally activated during oocyte maturation by proteins that recognize the conserved AAUAAA hexanucleotide and U-rich Cytoplasmic Polyadenylation Elements (CPEs) within cyclin B1 mRNA's 3'<b>U</b>n<b>T</b>ranslated <b>R</b>egion (3'<b>UTR</b>).</p> <p>Results</p> <p>The zebrafish cyclin B1 mRNA was polyadenylated during zebrafish oocyte maturation. Furthermore, the zebrafish cyclin B1 mRNA's 3'UTR was sufficient to stimulate translation of a reporter mRNA during zebrafish oocyte maturation. This stimulation required both AAUAAA and U-rich CPE-like sequences. However, in contrast to AAUAAA, the positions and sequences of the functionally defined CPEs were poorly conserved between <it>Xenopus </it>and zebrafish cyclin B1 mRNA 3'UTRs. To determine whether these differences were relevant to translation efficiency, we analyzed the translational activity of reporter mRNAs containing either the zebrafish or <it>Xenopus </it>cyclin B1 mRNA 3'UTRs during both zebrafish and <it>Xenopus </it>oocyte maturation. The zebrafish cyclin B1 3'UTR was quantitatively less effective at stimulating polyadenylation and translation compared to the <it>Xenopus </it>cyclin B1 3'UTR during both zebrafish and <it>Xenopus </it>oocyte maturation.</p> <p>Conclusion</p> <p>Although the factors that regulate translation of maternal mRNAs are highly conserved, the target sequences and overall sequence architecture within the 3'UTR of the cyclin B1 mRNA have diverged to affect translational efficiency, perhaps to optimize levels of cyclin B1 protein required by these different species during their earliest embryonic cell divisions.</p
A new determination of the orbit and masses of the Be binary system delta Scorpii
The binary star delta Sco (HD143275) underwent remarkable brightening in the
visible in 2000, and continues to be irregularly variable. The system was
observed with the Sydney University Stellar Interferometer (SUSI) in 1999,
2000, 2001, 2006 and 2007. The 1999 observations were consistent with
predictions based on the previously published orbital elements. The subsequent
observations can only be explained by assuming that an optically bright
emission region with an angular size of > 2 +/- 1 mas formed around the primary
in 2000. By 2006/2007 the size of this region grew to an estimated > 4 mas.
We have determined a consistent set of orbital elements by simultaneously
fitting all the published interferometric and spectroscopic data as well as the
SUSI data reported here. The resulting elements and the brightness ratio for
the system measured prior to the outburst in 2000 have been used to estimate
the masses of the components. We find Ma = 15 +/- 7 Msun and Mb = 8.0 +/- 3.6
Msun. The dynamical parallax is estimated to be 7.03 +/- 0.15 mas, which is in
good agreement with the revised HIPPARCOS parallax.Comment: 8 pages, 4 figs. Accepted for publication in MNRA
Multi-year characterisation of the broad-band emission from the intermittent extreme BL Lac 1ES~2344+514
The BL Lac 1ES 2344+514 is known for temporary extreme properties (e.g., a
shift of the synchrotron SED peak energy above 1keV). While
those extreme states were so far observed only during high flux levels,
additional multi-year observing campaigns are required to achieve a coherent
picture. Here, we report the longest investigation of the source from radio to
VHE performed so far, focusing on a systematic characterisation of the
intermittent extreme states. While our results confirm that 1ES 2344+514
typically exhibits 1keV during elevated flux periods, we also
find periods where the extreme state coincides with low flux activity. A strong
spectral variability thus happens in the quiescent state, and is likely caused
by an increase of the electron acceleration efficiency without a change in the
electron injection luminosity. We also report a strong X-ray flare (among the
brightest for 1ES 2344+514) without a significant shift of .
During this particular flare, the X-ray spectrum is among the softest of the
campaign. It unveils complexity in the spectral evolution, where the common
harder-when-brighter trend observed in BL Lacs is violated. During a low and
hard X-ray state, we find an excess of the UV flux with respect to an
extrapolation of the X-ray spectrum to lower energies. This UV excess implies
that at least two regions contribute significantly to the
infrared/optical/ultraviolet/X-ray emission. Using the simultaneous MAGIC,
XMM-Newton, NuSTAR, and AstroSat observations, we argue that a region possibly
associated with the 10 GHz radio core may explain such an excess. Finally, we
investigate a VHE flare, showing an absence of simultaneous variability in the
0.3-2keV band. Using a time-dependent leptonic modelling, we show that this
behaviour, in contradiction to single-zone scenarios, can instead be explained
by a two-component model.Comment: Accepted for publication in Astronomy & Astrophysic
MAGIC observations provide compelling evidence of hadronic multi-TeV emission from the putative PeVatron SNR G106.3+2.7
Context. Certain types of supernova remnants (SNRs) in our Galaxy are assumed to be PeVatrons, capable of accelerating cosmic rays (CRs) to ∼ PeV energies. However, conclusive observational evidence for this has not yet been found. The SNR G106.3+2.7, detected at 1- 100 TeV energies by different γ-ray facilities, is one of the most promising PeVatron candidates. This SNR has a cometary shape, which can be divided into a head and a tail region with different physical conditions. However, in which region the 100 TeV emission is produced has not yet been identified because of the limited position accuracy and/or angular resolution of existing observational data. Additionally, it remains unclear as to whether the origin of the γ-ray emission is leptonic or hadronic. Aims. With the better angular resolution provided by new MAGIC data compared to earlier γ-ray datasets, we aim to reveal the acceleration site of PeV particles and the emission mechanism by resolving the SNR G106.3+2.7 with 0.1 resolution at TeV energies. Methods. We observed the SNR G106.3+2.7 using the MAGIC telescopes for 121.7 h in total - after quality cuts - between May 2017 and August 2019. The analysis energy threshold is ∼0.2 TeV, and the angular resolution is 0.07-0.1. We examined the γ-ray spectra of different parts of the emission, whilst benefitting from the unprecedented statistics and angular resolution at these energies provided by our new data. We also used measurements at other wavelengths such as radio, X-rays, GeV γ-rays, and 10 TeV γ-rays to model the emission mechanism precisely. Results. We detect extended γ-ray emission spatially coincident with the radio continuum emission at the head and tail of SNR G106.3+2.7. The fact that we detect a significant γ-ray emission with energies above 6.0 TeV from only the tail region suggests that the emissions above 10 TeV detected with air shower experiments (Milagro, HAWC, Tibet ASγ and LHAASO) are emitted only from the SNR tail. Under this assumption, the multi-wavelength spectrum of the head region can be explained with either hadronic or leptonic models, while the leptonic model for the tail region is in contradiction with the emission above 10 TeV and X-rays. In contrast, the hadronic model could reproduce the observed spectrum at the tail by assuming a proton spectrum with a cutoff energy of ∼1 PeV for that region. Such high-energy emission in this middle-aged SNR (4-10 kyr) can be explained by considering a scenario where protons escaping from the SNR in the past interact with surrounding dense gases at present. Conclusions. The γ-ray emission region detected with the MAGIC telescopes in the SNR G106.3+2.7 is extended and spatially coincident with the radio continuum morphology. The multi-wavelength spectrum of the emission from the tail region suggests proton acceleration up to ∼PeV, while the emission mechanism of the head region could either be hadronic or leptonic
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