Investigating the inner discs of Herbig Ae/Be stars with CO bandhead and Br Gamma emission

Herbig Ae/Be stars lie in the mass range between low and high mass young stars, and therefore offer a unique opportunity to observe any changes in the formation processes that may occur across this boundary. This paper presents medium resolution VLT/X-Shooter spectra of six Herbig Ae/Be stars, drawn from a sample of 91 targets, and high resolution VLT/CRIRES spectra of five Herbig Ae/Be stars, chosen based on the presence of CO first overtone bandhead emission in their spectra. The X-Shooter survey reveals a low detection rate of CO first overtone emission (7 per cent), consisting of objects mainly of spectral type B. A positive correlation is found between the strength of the CO v=2-0 and Br {\gamma} emission lines, despite their intrinsic linewidths suggesting a separate kinematic origin. The high resolution CRIRES spectra are modelled, and are well fitted under the assumption that the emission originates from small scale Keplerian discs, interior to the dust sublimation radius, but outside the co-rotation radius of the central stars. In addition, our findings are in very good agreement for the one object where spatially resolved near-infrared interferometric studies have also been performed. These results suggest that the Herbig Ae/Be stars in question are in the process of gaining mass via disc accretion, and that modelling of high spectral resolution spectra is able to provide a reliable probe into the process of stellar accretion in young stars of intermediate to high masses.Comment: Accepted for publication in MNRAS. 14 pages, 5 figure

Activation of bicyclic nitro-drugs by a novel nitroreductase (NTR2) in <i>Leishmania</i>

Drug discovery pipelines for the "neglected diseases" are now heavily populated with nitroheterocyclic compounds. Recently, the bicyclic nitro-compounds (R)-PA-824, DNDI-VL-2098 and delamanid have been identified as potential candidates for the treatment of visceral leishmaniasis. Using a combination of quantitative proteomics and whole genome sequencing of susceptible and drug-resistant parasites we identified a putative NAD(P)H oxidase as the activating nitroreductase (NTR2). Whole genome sequencing revealed that deletion of a single cytosine in the gene for NTR2 that is likely to result in the expression of a non-functional truncated protein. Susceptibility of leishmania was restored by reintroduction of the wild-type gene into the resistant line, which was accompanied by the ability to metabolise these compounds. Overexpression of NTR2 in wild-type parasites rendered cells hyper-sensitive to bicyclic nitro-compounds, but only marginally to the monocyclic nitro-drugs, nifurtimox and fexinidazole sulfone, known to be activated by a mitochondrial oxygen-insensitive nitroreductase (NTR1). Conversely, a double knockout NTR2 null cell line was completely resistant to bicyclic nitro-compounds and only marginally resistant to nifurtimox. Sensitivity was fully restored on expression of NTR2 in the null background. Thus, NTR2 is necessary and sufficient for activation of these bicyclic nitro-drugs. Recombinant NTR2 was capable of reducing bicyclic nitro-compounds in the same rank order as drug sensitivity in vitro. These findings may aid the future development of better, novel anti-leishmanial drugs. Moreover, the discovery of anti-leishmanial nitro-drugs with independent modes of activation and independent mechanisms of resistance alleviates many of the concerns over the continued development of these compound series

On the origin of the correlations between the accretion luminosity and emission line luminosities in pre-main-sequence stars

Correlations between the accretion luminosity and emission line luminosities (Lacc and Lline) of pre-main-sequence (PMS) stars have been published for many different spectral lines, which are used to estimate accretion rates. Despite the origin of those correlations is unknown, this could be attributed to direct or indirect physical relations between the emission line formation and the accretion mechanism. This work shows that all (near-UV/optical/near-IR) Lacc-Lline correlations are the result of the fact that the accretion luminosity and the stellar luminosity (L*) are correlated, and are not necessarily related with the physical origin of the line. Synthetic and observational data are used to illustrate how the Lacc-Lline correlations depend on the Lacc-L* relationship. We conclude that because PMS stars show the Lacc-L* correlation immediately implies that Lacc also correlates with the luminosity of all emission lines, for which the Lacc-Lline correlations alone do not prove any physical connection with accretion but can only be used with practical purposes to roughly estimate accretion rates. When looking for correlations with possible physical meaning, we suggest that Lacc/L* and Lline/L* should be used instead of Lacc and Lline. Finally, the finding that Lacc has a steeper dependence on L* for T Tauri stars than for intermediate-mass Herbig Ae/Be stars is also discussed. That is explained from the magnetospheric accretion scenario and the different photospheric properties in the near-U

High-resolution Br γ spectro-interferometry of the transitional Herbig Ae/Be star HD 100546: a Keplerian gaseous disc inside the inner rim

We present spatially and spectrally resolved Br γ emission around the planet-hosting, transitional Herbig Ae/Be star HD 100546. Aiming to gain insight into the physical origin of the line in possible relation to accretion processes, we carried out Br γ spectro-interferometry using AMBER/VLTI from three different baselines achieving spatial and spectral resolutions of 2–4 mas and 12 000. The Br γ visibility is larger than that of the continuum for all baselines. Differential phases reveal a shift between the photocentre of the Br γ line – displaced ∼0.6 mas (0.06 au at 100 pc) NE from the star – and that of the K-band continuum emission – displaced ∼0.3 mas NE from the star. The photocentres of the redshifted and blueshifted components of the Br γ line are located NW and SE from the photocentre of the peak line emission, respectively. Moreover, the photocentre of the fastest velocity bins within the spectral line tends to be closer to that of the peak emission than the photocentre of the slowest velocity bins. Our results are consistent with a Br γ-emitting region inside the dust inner rim ( ≲ 0.25 au) and extending very close to the central star, with a Keplerian, disc-like structure rotating counter-clockwise, and most probably flared (∼25°). Even though the main contribution to the Br γ line does not come from gas magnetically channelled on to the star, accretion on to HD 100546 could be magnetospheric, implying a mass accretion rate of a few 10−7 M⊙ yr−1. This value indicates that the observed gas has to be replenished on time-scales of a few months to years, perhaps by planet-induced flows from the outer to the inner disc as has been reported for similar systems

Systems analysis of metabolism in the pathogenic trypanosomatid Leishmania major

Systems analyses have facilitated the characterization of metabolic networks of several organisms. We have reconstructed the metabolic network of Leishmania major, a poorly characterized organism that causes cutaneous leishmaniasis in mammalian hosts. This network reconstruction accounts for 560 genes, 1112 reactions, 1101 metabolites and 8 unique subcellular localizations. Using a systems-based approach, we hypothesized a comprehensive set of lethal single and double gene deletions, some of which were validated using published data with approximately 70% accuracy. Additionally, we generated hypothetical annotations to dozens of previously uncharacterized genes in the L. major genome and proposed a minimal medium for growth. We further demonstrated the utility of a network reconstruction with two proof-of-concept examples that yielded insight into robustness of the network in the presence of enzymatic inhibitors and delineation of promastigote/amastigote stage-specific metabolism. This reconstruction and the associated network analyses of L. major is the first of its kind for a protozoan. It can serve as a tool for clarifying discrepancies between data sources, generating hypotheses that can be experimentally validated and identifying ideal therapeutic targets

Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal–antiplasmodial activity.

YesDual submicromolar trypanocidal–antiplasmodial compounds have been identified by screening and chemical synthesis of 4-aminoquinoline-based heterodimeric compounds of three different structural classes. In Trypanosoma brucei, inhibition of the enzyme trypanothione reductase seems to be involved in the potent trypanocidal activity of these heterodimers, although it is probably not the main biological target. Regarding antiplasmodial activity, the heterodimers seem to share the mode of action of the antimalarial drug chloroquine, which involves inhibition of the haem detoxification process. Interestingly, all of these heterodimers display good brain permeabilities, thereby being potentially useful for late stage human African trypanosomiasis. Future optimization of these compounds should focus mainly on decreasing cytotoxicity and acetylcholinesterase inhibitory activity

On the origin of the correlations between the accretion luminosity and emission line luminosities in pre-main-sequence stars

Correlations between the accretion luminosity and emission line luminosities (Lacc and Lline) of pre-main-sequence (PMS) stars have been published for many different spectral lines, which are used to estimate accretion rates. Despite the origin of those correlations is unknown, this could be attributed to direct or indirect physical relations between the emission line formation and the accretion mechanism. This work shows that all (near-UV/optical/near-IR) Lacc–Lline correlations are the result of the fact that the accretion luminosity and the stellar luminosity (L*) are correlated, and are not necessarily related with the physical origin of the line. Synthetic and observational data are used to illustrate how the Lacc–Lline correlations depend on the Lacc–L* relationship. We conclude that because PMS stars show the Lacc–L* correlation immediately implies that Lacc also correlates with the luminosity of all emission lines, for which the Lacc–Lline correlations alone do not prove any physical connection with accretion but can only be used with practical purposes to roughly estimate accretion rates. When looking for correlations with possible physical meaning, we suggest that Lacc/L* and Lline/L* should be used instead of Lacc and Lline. Finally, the finding that Lacc has a steeper dependence on L* for T Tauri stars than for intermediate-mass Herbig Ae/Be stars is also discussed. That is explained from the magnetospheric accretion scenario and the different photospheric properties in the near-UV