The chikungunya virus (CHIKV) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. We discovered a ...novel class of small molecules (1,2,3triazolo4,5-dpyrimidin-7(6H)-ones) with potent in vitro activity against CHIKV isolates from different geographical regions. Drug-resistant variants were selected and these carried a P34S substitution in non-structural protein 1 (nsP1), the main enzyme involved in alphavirus RNA capping. Biochemical assays using nsP1 of the related Venezuelan equine encephalitis virus revealed that the compounds specifically inhibit the guanylylation of nsP1. This is, to the best of our knowledge, the first report demonstrating that the alphavirus capping machinery is an excellent antiviral drug target. Considering the lack of options to treat CHIKV infections, this series of compounds with their unique (alphavirus-specific) target offers promise for the development of therapy for CHIKV infections.
Background
Detection of chromosomal abnormalities is crucial in various medical areas; to diagnose birth defects, genetic disorders, and infertility, among other complex phenotypes, in individuals ...across a wide range of ages. Hence, the present study wants to contribute to the knowledge of type and frequency of chromosomal alterations and polymorphisms in Ecuador.
Methods
Cytogenetic registers from different Ecuadorian provinces have been merged and analyzed to construct an open‐access national registry of chromosome alterations and polymorphisms.
Results
Of 28,806 karyotypes analyzed, 6,008 (20.9%) exhibited alterations. Down syndrome was the most frequent autosome alteration (88.28%), followed by Turner syndrome (60.50%), a gonosome aneuploidy. A recurrent high percentage of Down syndrome mosaicism (7.45%) reported here, as well as by previous Ecuadorian preliminary registries, could be associated with geographic location and admixed ancestral composition. Translocations (2.46%) and polymorphisms (7.84%) were not as numerous as autosomopathies (64.33%) and gonosomopathies (25.37%). Complementary to conventional cytogenetics tests, molecular tools have allowed identification of submicroscopic alterations regions or candidate genes which can be possibly implicated in patients' symptoms and phenotypes.
Conclusion
The Ecuadorian National Registry of Chromosome Alterations and Polymorphisms provides a baseline to better understand chromosomal abnormalities in Ecuador and therefore their clinical management and awareness. This data will guide public policy makers to promote and financially support cytogenetic and genetic testing.
Of 28,806 karyotypes analyzed in Ecuador, 6,008 (20.9%) exhibited alterations. Down syndrome was the most frequent autosome alteration (88.28%), followed by Turner syndrome (60.50%). Translocations (2.46%) and polymorphisms (7.84%) were not as numerous as autosomopathies (64.33%) and gonosomopathies (25.37%).
This study was design to investigate the “in vitro” effect of bisphenol A (BPA), a component of resin used in dentistry, on viability, and substrate adherence capacity of macrophages. Peritoneal ...macrophages were obtained from Wistar rats and resuspended in RPMI-1640 medium. Viability was determined by trypan blue exclusion. As a test of macrophage adhesion, the adherence capacity of macrophages to a plastic surface was determined and the adherence index was calculated. Assays were conducted in Eppendorf tubes for 60 min of incubation at 37°C in a humidified atmosphere of 5% CO
2 in air. BPA did not alter significantly macrophage viability at concentrations as high as 10
−5
M, but BPA decreased in a dose-dependent manner the adherence index of rat peritoneal macrophages. Control peritoneal macrophages showed an adherence index = 81.5 ± 7.9%. In the presence of 10
−8
M BPA, the AI of macrophages decreased to 41.4 ± 12.2% (p < 0.05). Higher BPA concentrations (10
−7 to 10
−5
M) also caused a significant inhibition of the adherence index. Half-maximal inhibition (IC
50) was obtained at 4.92 ± 0.39 × 10
−6
M BPA. The in vitro study shows that the resin component BPA can alter macrophage adhesion. Taking into account that adhesion is the first step in the phagocytic process of macrophages and in antigen presentation, BPA could inhibit macrophage function and modulate immune and inflammatory responses in dental pulp and periapical tissues.
The neutron-induced fission cross section of 237Np was experimentally determined at the high-resolutionand high-intensity facility n TOF, at CERN, in the energy range 100 keV to 9 MeV, using the ...235U(n,f ) and 238U(n,f ) cross section standards below and above 2 MeV, respectively. A fast ionization chamber was usedin order to detect the fission fragments from the reactions and the targets were characterized as far as theirmass and homogeneity are concerned by means of α spectroscopy and Rutherford backscattering spectroscopyrespectively. Theoretical calculations within the Hauser-Feshbach formalism have been performed, employingthe EMPIRE code, and the model parameters were tuned in order to successfully reproduce the experimental fissioncross-sectional data and simultaneously all the competing reaction channels.
.
The neutron-induced fission cross-section of
241
Am has been measured relative to the standard fission cross-section of
235
U between 0.5 and 20MeV. The experiment was performed at the CERN n_TOF ...facility. Fission fragments were detected by a fast ionization chamber by discriminating against the
-particles from the high radioactivity of the samples. The high instantaneous neutron flux and the low background of the n_TOF facility enabled us to obtain uncertainties of
5%. With the present results it was possible to resolve discrepancies between previous data sets and to confirm current evaluations, thus providing important information for design studies of future reactors with improved fuel burn-up.
The cross section of the reaction {sup 197}Au(n,{gamma}) was measured with the time-of-flight technique at the n{_}TOF (neutron time-of-flight) facility in the unresolved resonance region between 5 ...and 400 keV using a pair of C{sub 6}D{sub 6} (where D denotes {sup 2}H) liquid scintillators for the detection of prompt capture {gamma} rays. The results with a total uncertainty of 3.9%-6.7% for a resolution of 20 bins per energy decade show fair agreement with the Evaluated Nuclear Data File Version B-VII.0 (ENDF/B-VII.0), which contains the standard evaluation. The Maxwellian-averaged cross section (MACS) at 30 keV is in excellent agreement with the one according to the ENDF/B-VII.0 evaluation and 4.7% higher than the MACS measured independently by activation technique. Structures in the cross section, which had also been reported earlier, have been interpreted as being due to clusters of resonances.
A low-cost high-capacity 24 GHz transceiver system was described, designed, built and experimentally characterized. The system was modelled after the continuous-wave frequency modulation (CWFM) radar ...architecture and was modified to allow data transmission in full-duplex mode. The proposed system was built including the 24 GHz front-end and the intermediate frequency subsystems. It was made using microstrip hybrid technology on 10 mils RT/Duroid 6006 substrate and 300 mu m via holes. Performance results indicated that the transceivers could attain BER of 10 super(-8) in full-duplex links within a 5 km range on employing 40 cm-diameter parabolic antennas.
Neutron resonance analyses have been performed for the capture cross sections of 186Os, 187Os, and 188Os measured at the n TOF facility at CERN. Resonance parameters have been extracted up to 5, 3, ...and 8 keV, respectively, using the SAMMY code for a full R-matrix fit of the capture yields. From these results average resonance parameters were derived by a statistical analysis to provide a comprehensive experimental basis for modeling of the stellar neutron capture rates of these isotopes in terms of the Hauser-Feshbach statistical model. Consistent calculations for the capture and inelastic reaction channels are crucial for the evaluation of stellar enhancement factors to correct the Maxwellian averaged cross sections obtained from experimental data for the effect of thermally populated excited states. These factors have been calculated for the full temperature range of current scenarios of s-process nucleosynthesis using the combined information of the experimental data in the region of resolved resonances and in the continuum. The consequences of this analysis for the s-process component of the 187Os abundance and the related impact on the evaluation of the time duration of galactic nucleosynthesis via the Re/Os cosmochronometer are discussed.
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