Comparative evaluation of therapeutic DNA vaccines against Trypanosoma cruzi in mice

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health problem in most of Latin America. A key priority is the development of new treatments, due to the poor efficacy of current ones. We report here the comparative evaluation of therapeutic DNA vaccines encoding various T. cruzi antigens. ICR mice infected with 500 parasites intraperitoneally were treated at 5 and 12 days postinfection with 20 mu g of plasmid DNA encoding T. cruzi antigens TSA-1, TS, ASP-2-like, Tc52 or Tc24. Treatment with plasmid encoding TS and/or ASP-2-like antigens had no significant effect on parasitemia or survival. Treatment with Tc52 DNA significantly reduced parasitemia, as well as cardiac parasite burden, and improved survival, although myocarditis was not significantly affected. Finally, treatment with plasmids encoding Tc24 and TSA-1 induced the most complete control of disease as evidenced by significant reductions in parasitemia, mortality, myocarditis and heart parasite burden. These data demonstrate that therapeutic vaccine efficacy is dependent on the antigen and suggest that DNA vaccines encoding Tc24, TSA-1, and Tc52 represent the best candidates for further studies of a therapeutic vaccine against Chagas disease.Univ Autonoma Yucatan, Parasitol Lab, Ctr Invest Reg Dr Hideyo Noguchi, Merida, Yucatan, MexicoINSERM, IRD, UR 008, Ctr IRD Montpellier, Montpellier, FranceUniversidade Federal de São Paulo, CINTERGEN, Dept Microbiol Inmunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, CINTERGEN, Dept Microbiol Inmunol & Parasitol, São Paulo, BrazilWeb of Scienc

In Vitro and In Silico Analysis of New n-Butyl and Isobutyl Quinoxaline-7-carboxylate 1,4-di-N-oxide Derivatives against Trypanosoma cruzi as Trypanothione Reductase Inhibitors

American trypanosomiasis is a worldwide health problem that requires attention due to ineffective treatment options. We evaluated n-butyl and isobutyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives against trypomastigotes of the Trypanosoma cruzi strains NINOA and INC-5. An in silico analysis of the interactions of 1,4-di-N-oxide on the active site of trypanothione reductase (TR) and an enzyme inhibition study was carried out. The n-butyl series compound identified as T-150 had the best trypanocidal activity against T. cruzi trypomastigotes, with a 13% TR inhibition at 44 μM. The derivative T-147 behaved as a mixed inhibitor with Ki and Ki' inhibition constants of 11.4 and 60.8 µM, respectively. This finding is comparable to the TR inhibitor mepacrine (Ki = 19 µM)

Validity of the Maternal Antenatal Attachment Scale-Spanish Version for Mexican Pregnant Women

During pregnancy, parents experiment emotions, thoughts, and behaviors related to their unborn child as precursors of attachment in the caretaker-infant dyad. The Maternal Antenatal Attachment Scale (MAAS) is an instrument that has shown adequate psychometric properties to evaluate this construct in developed countries. The aim of this study was to assess the reliability and concurrent validity of the Maternal Antenatal Attachment Scale-Spanish version for Mexican women (MAAS-Spanish version). A sample of 142 women in their third trimester of pregnancy who received care in a tertiary hospital was selected. The full scale of the MAAS-Spanish version obtained a Cronbach alpha of .79. A significant negative correlation was found between the global MAAS-Spanish version score (r = -.23, p ≤ .01) and the Postpartum Depression Predictors Inventory-Revised and depressive symptoms (r = -.36 , p ≤ .01). The translated and adapted scale has adequate internal consistency and concurrent validity to measure this construct in this population

Search for Decaying Dark Matter in the Virgo Cluster of Galaxies with HAWC

The decay or annihilation of dark matter particles may produce a steady flux of very-high-energy gamma rays detectable above the diffuse background. Nearby clusters of galaxies provide excellent targets to search for the signatures of particle dark matter interactions. In particular, the Virgo cluster spans several degrees across the sky and can be efficiently probed with a wide field-of-view instrument. The High Altitude Water Cherenkov (HAWC) observatory, due to its wide field of view and sensitivity to gamma rays at an energy scale of 300 GeV--100 TeV is well-suited for this search. Using 2141 days of data, we search for gamma-ray emission from the Virgo cluster, assuming well-motivated dark matter sub-structure models. Our results provide some of the strongest constraints on the decay lifetime of dark matter for masses above 10 TeV.Comment: 7 pages, 3 figures. Submitted to PR

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

Validation of standardized data formats and tools for ground-level particle-based gamma-ray observatories

Ground-based gamma-ray astronomy is still a rather young field of research,with strong historical connections to particle physics. This is why mostobservations are conducted by experiments with proprietary data and analysissoftware, as it is usual in the particle physics field. However in recentyears, this paradigm has been slowly shifting towards the development and useof open-source data formats and tools, driven by upcoming observatories such asthe Cherenkov Telescope Array (CTA). In this context, a community-driven,shared data format (the gamma-astro-data-format or GADF) and analysis toolssuch as Gammapy and ctools have been developed. So far these efforts have beenled by the IACT community, leaving out other types of ground-based gamma-rayinstruments.We aim to show that the data from ground particle arrays, such asthe High-Altitude Water Cherenkov (HAWC) observatory, is also compatible withthe GADF and can thus be fully analysed using the related tools, in this caseGammapy. We reproduce several published HAWC results using Gammapy and dataproducts compliant with GADF standard. We also illustrate the capabilities ofthe shared format and tools by producing a joint fit of the Crab spectrumincluding data from six different gamma-ray experiments. We find excellentagreement with the reference results, a powerful check of both the publishedresults and the tools involved. The data from particle detector arrays such asthe HAWC observatory can be adapted to the GADF and thus analysed with Gammapy.A common data format and shared analysis tools allow multi-instrument jointanalysis and effective data sharing. Given the complementary nature of pointingand wide-field instruments, this synergy will be distinctly beneficial for thejoint scientific exploitation of future observatories such as the SouthernWide-field Gamma-ray Observatory and CTA.<br

High Altitude characterization of the Hunga Pressure Wave with Cosmic Rays by the HAWC Observatory

High-energy cosmic rays that hit the Earth can be used to study large-scale atmospheric perturbations. After a first interaction in the upper parts of the atmosphere, cosmic rays produce a shower of particles that sample the atmosphere down to the detector level. The HAWC (High-Altitude Water Cherenkov) cosmic-ray observatory in Central Mexico at 4,100 m elevation detects air shower particles continuously with 300 water Cherenkov detectors with an active area of 12,500 m$^{2}$. On January 15th, 2022, HAWC detected the passage of the pressure wave created by the explosion of the Hunga volcano in the Tonga islands, 9,000 km away, as an anomaly in the measured rate of shower particles. The HAWC measurements are used to characterize the shape of four pressure wave passages, determine the propagation speed of each one, and correlate the variations of the shower particle rates with the barometric pressure changes, extracting a barometric parameter. The profile of the shower particle rate and atmospheric pressure variations for the first transit of the pressure wave at HAWC is compared to the pressure measurements at Tonga island, near the volcanic explosion. This work opens the possibility of using large particle cosmic-ray air shower detectors to trace large atmospheric transient waves.Comment: Contact about this analysis: A. Sandoval ([email protected]), A. Lara ([email protected]) & H. Le\'on Vargas ([email protected]