Long-term monitoring of the outgassing and composition of comet 67P/Churyumov-Gerasimenko with the Rosetta/MIRO instrument

We present the analysis of ≈100 molecular maps of the coma of comet 67P/Churyumov-Gerasimenko that were obtained with the MIRO submillimeter radiotelescope on board the Rosetta spacecraft. From the spectral line mapping of H216O, H218O, H217O, CH3OH, NH3, and CO and some fixed nadir pointings, we retrieved the outgassing pattern and total production rates for these species. The analysis covers the period from July 2014, inbound to perihelion, to June 2016, outbound, and heliocentric distances rh = 1.24–3.65 AU. A steep evolution of the outgassing rates with heliocentric distance is observed, typically in rh−16, with significant differences between molecules (e.g. steeper variation for H2O post-perihelion than for methanol). As a consequence, the abundances relative to water in the coma vary. The CH3OH and CO abundances increase after perihelion, while the NH3 abundance peaks around perihelion and then decreases. Outgassing patterns have been modeled as 2D Gaussian jets. The width of these jets is maximum around the equinoxes when the bulk of the outgassing is located near the equator. From July 2014 to February 2015, the outgassing is mostly restricted to a narrower jet (full width at half-maximum ≈80°) originating from high northern latitudes, while around perihelion, most of the gaseous production comes from the southernmost regions ( − 80 ± 5° cometocentric latitude) and forms a 100°–130° (full width at half-maximum) wide fan. We find a peak production of water of 0.8 × 1028 molec. s−1, 2.5 times lower than measured by the ROSINA experiment, and place an upper limit to a 50% additional production that could come from the sublimation of icy grains. We estimate the total loss of ices during this perihelion passage to be 4.18 ± 0.18 × 109 kg. We derive a dust-to-gas ratio in the lost material of 0.7–2.3 (including all sources of errors) based on the nucleus mass loss of 10.5 ± 3.4 × 109 kg estimated by the RSI experiment. We also obtain an estimate of the H218O/H217O ratio of 5.6 ± 0.8.

Cooperation between T cell receptor and Toll-like receptor 5 signaling for CD4+ T cell activation

CD4+ T cells recognize antigens through their T cell receptors (TCRs); however, additional signals involving costimulatory receptors, for example, CD28, are required for proper T cell activation. Alternative costimulatory receptors have been proposed, including members of the Toll-like receptor (TLR) family, such as TLR5 and TLR2. To understand the molecular mechanism underlying a potential costimulatory role for TLR5, we generated detailed molecular maps and logical models for the TCR and TLR5 signaling pathways and a merged model for cross-interactions between the two pathways. Furthermore, we validated the resulting model by analyzing how T cells responded to the activation of these pathways alone or in combination, in terms of the activation of the transcriptional regulators CREB, AP-1 (c-Jun), and NF-κB (p65). Our merged model accurately predicted the experimental results, showing that the activation of TLR5 can play a similar role to that of CD28 activation with respect to AP-1, CREB, and NF-κB activation, thereby providing insights regarding the cross-regulation of these pathways in CD4+ T cells.

Histochemistry today: Detection and location of single molecules

Especially in the latest years, histochemical investigations have progressively been oriented toward the visualization and quantitative assessment of single molecules, thanks to the availability of stains, reactions and procedures allowing to detect in situ proteins, or carboydrates or nucleic acid sequences with high specificity. This is evident from the recent literature, where in the large majority of the published articles immunohistochemistry, lectin histochemistry or fluorescence in situ hybridization were used as experimental methodologies. Since in biomedical research it is crucial to specifically label and localize molecules there, where they exert their structural roles and activities, histochemistry will continue to provide scientists the most appropriate tools for tracing molecular maps suitable for reaching a mechanistic explanation of cell functions in tissues.

Signalling maps in cancer research: construction and data analysis

Generation and usage of high-quality molecular signalling network maps can be augmented by standardising notations, establishing curation workflows and application of computational biology methods to exploit the knowledge contained in the maps. In this manuscript, we summarize the major aims and challenges of assembling information in the form of comprehensive maps of molecular interactions. Mainly, we share our experience gained while creating the Atlas of Cancer Signalling Network. In the step-by-step procedure, we describe the map construction process and suggest solutions for map complexity management by introducing a hierarchical modular map structure. In addition, we describe the NaviCell platform, a computational technology using Google Maps API to explore comprehensive molecular maps similar to geographical maps, and explain the advantages of semantic zooming principles for map navigation. We also provide the outline to prepare signalling network maps for navigation using the NaviCell platform. Finally, several examples of cancer high-throughput data analysis and visualization in the context of comprehensive signalling maps are presented.

Computational and Investigative Study of Flavonoids Active against Trypanosoma cruzi and Leishmania spp

Flavonoid compounds active against Trypanosoma cruzi and Leishmania species were submitted to several methodologies in silico: docking with the enzymes cruzain and trypanothione reductase (from T. cruzi), and N-myristoyltransferase, dihydroorotate dehydrogenase, and trypanothiona reductase (from Leishmania spp). Molecular maps of the complexes and the ligands were calculated. In order to compare and evaluate the antioxidant activity of the flavonoids with their antiprotozoal activity, quantum parameters were calculated. Considering the energies, interactions, and hydrophobic surfaces calculated, the flavonoids chrysin dimethyl ether against T. cruzi, and ladanein against Leishmania sp. presented the best results. The antioxidant activity did not show any correlation with anti-parasitic activity; only chrysin and its dimethyl ether showed favorable anti-parasitic results. This study hopes to contribute to existing research on these natural products against these tropical parasites.