Fragment screening reveals salicylic hydroxamic acid as an inhibitor of <em>Trypanosoma brucei</em> GPI GlcNAc-PI de-N-acetylase

The zinc-metalloenzyme GlcNAc-PI de-N-acetylase is essential for the biosynthesis of mature GPI anchors and has been genetically validated in the bloodstream form of Trypanosoma brucei, which causes African sleeping sickness. We screened a focused library of zinc-binding fragments and identified salicylic hydroxamic acid as a GlcNAc-PI de-N-acetylase inhibitor with high ligand efficiency. This is the first small molecule inhibitor reported for the trypanosome GPI pathway. Investigating the structure activity relationship revealed that hydroxamic acid and 2-OH are essential for potency, and that substitution is tolerated at the 4- and 5-positions

Thermal entanglement in a triple quantum dot system

We present studies of thermal entanglement of a three-spin system in triangular symmetry. Spin correlations are described within an effective Heisenberg Hamiltonian, derived from the Hubbard Hamiltonian, with super-exchange couplings modulated by an effective electric field. Additionally a homogenous magnetic field is applied to completely break the degeneracy of the system. We show that entanglement is generated in the subspace of doublet states with different pairwise spin correlations for the ground and excited states. At low temperatures thermal mixing between the doublets with the same spin destroys entanglement, however one can observe its restoration at higher temperatures due to the mixing of the states with an opposite spin orientation or with quadruplets (unentangled states) always destroys entanglement. Pairwise entanglement is quantified using concurrence for which analytical formulae are derived in various thermal mixing scenarios. The electric field plays a specific role -- it breaks the symmetry of the system and changes spin correlations. Rotating the electric field can create maximally entangled qubit pairs together with a separate spin (monogamy) that survives in a relatively wide temperature range providing robust pairwise entanglement generation at elevated temperatures.Comment: 9 pages, 5 figures, accepted in Eur. Phys. J.

Vacancy defects in epitaxial thin film CuGaSe2 and CuInSe2

Epitaxial thin film CuGaSe2 and CuInSe2 samples grown on GaAs substrates with varying [Cu]/[Ga,In] ratios were studied using positron annihilation Doppler-broadening spectroscopy and were compared to bulk crystals. We find both Cu monovacancies and Cu-Se divacancies in CuInSe2, whereas, in CuGaSe2, the only observed vacancy defect is the Cu-Se divacancy.Peer reviewe

Towards integration of research and monitoring at forest ecosystems in Europe

Aim of study: The main aim of the work was to summarize availability, quality and comparability of on-going European Research and Monitoring Networks (ERMN), based on the results of a COST FP0903 Action questionnaire carried out in September 2010 and May 2012. Area of study: The COST Action FP0903 involves 29 European countries and 4 non-COST institutions from USA, Morocco and Tunisia. In this study, the total of 22 replies to the questionnaire from 18 countries were included. Materials and methods: Based on the feedback from the Action FP0903 countries, the most popular European Networks were identified. Thereafter, the access to the network database, available quality assurance/quality control procedures and publication were described. Finally, the so-called “Supersites” concept, defined as a “highly instrumented research infrastructure, for both research and monitoring of soil-plant-atmosphere interactions” was discussed. Main results: The result of the survey indicate that the vast majority of the Action FP0903 countries participate in the International Cooperative Programme on Assessment and Monitoring of Air Pollution Effects on Forest (ICP Forest). The multi-disciplinary International Cooperative Programme on Integrated Monitoring of Air Pollution Effects on Ecosystems (ICPIM) is the second most widespread forest programme. Research highlights: To fully understand biochemical cycles in forest ecosystems, long-term monitoring is needed. Hence, a network of “Supersites”, is proposed. The application of the above infrastructure can be an effective way to attain a better integration of research and monitoring networks at forest sites in Europ

Identification and functional characterization of a highly divergent N-acetylglucosaminyltransferase I (TbGnTI) in <em>Trypanosoma brucei</em>

Trypanosoma brucei expresses a diverse repertoire of N-glycans, ranging from oligomannose and paucimannose structures to exceptionally large complex N-glycans. Despite the presence of the latter, no obvious homologues of known β1–4-galactosyltransferase or β1–2- or β1–6-N-acetylglucosaminyltransferase genes have been found in the parasite genome. However, we previously reported a family of putative UDP-sugar-dependent glycosyltransferases with similarity to the mammalian β1–3-glycosyltransferase family. Here we characterize one of these genes, TbGT11, and show that it encodes a Golgi apparatus resident UDP-GlcNAc:α3-d-mannoside β1–2-N-acetylglucosaminyltransferase I activity (TbGnTI). The bloodstream-form TbGT11 null mutant exhibited significantly modified protein N-glycans but normal growth in vitro and infectivity to rodents. In contrast to multicellular organisms, where the GnTI reaction is essential for biosynthesis of both complex and hybrid N-glycans, T. brucei TbGT11 null mutants expressed atypical “pseudohybrid” glycans, indicating that TbGnTII activity is not dependent on prior TbGnTI action. Using a functional in vitro assay, we showed that TbGnTI transfers UDP-GlcNAc to biantennary Man(3)GlcNAc(2), but not to triantennary Man(5)GlcNAc(2), which is the preferred substrate for metazoan GnTIs. Sequence alignment reveals that the T. brucei enzyme is far removed from the metazoan GnTI family and suggests that the parasite has adapted the β3-glycosyltransferase family to catalyze β1–2 linkages

High-confidence glycosome proteome for procyclic form <em>Trypanosoma brucei</em> by epitope-tag organelle enrichment and SILAC proteomics

The glycosome of the pathogenic African trypanosome Trypanosoma brucei is a specialized peroxisome that contains most of the enzymes of glycolysis and several other metabolic and catabolic pathways. The contents and transporters of this membrane-bounded organelle are of considerable interest as potential drug targets. Here we use epitope tagging, magnetic bead enrichment, and SILAC quantitative proteomics to determine a high-confidence glycosome proteome for the procyclic life cycle stage of the parasite using isotope ratios to discriminate glycosomal from mitochondrial and other contaminating proteins. The data confirm the presence of several previously demonstrated and suggested pathways in the organelle and identify previously unanticipated activities, such as protein phosphatases. The implications of the findings are discussed

The Great Observatories Origins Deep Survey. VLT/FORS2 Spectroscopy in the GOODS-South Field: Part III

Aims. We present the full data set of the spectroscopic campaign of the ESO/GOODS program in the GOODS-South field, obtained with the FORS2 spectrograph at the ESO/VLT. Method. Objects were selected as candidates for VLT/FORS2 observations primarily based on the expectation that the detection and measurement of their spectral features would benefit from the high throughput and spectral resolution of FORS2. The reliability of the redshift estimates is assessed using the redshift-magnitude and color-redshift diagrams, and comparing the results with public data. Results. Including the third part of the spectroscopic campaign (12 masks) to the previous work (26 masks, Vanzella et al. 2005, 2006), 1715 spectra of 1225 individual targets have been analyzed. The actual spectroscopic catalog provides 887 redshift determinations. The typical redshift uncertainty is estimated to be sigma(z) ~ 0.001. Galaxies have been selected adopting different color criteria and using photometric redshifts. The resulting redshift distribution typically spans two domains: from z=0.5 to 2 and z=3.5 to 6.3. The reduced spectra and the derived redshifts are released to the community through the ESO web page http://www.eso.org/science/goods/Comment: 11 pages, 11 figures; accepted for publication in Astronomy & Astrophysics. Data are available at http://www.eso.org/science/goods

Routine Antenatal Anti-D Prophylaxis in Women Who Are Rh(D) Negative: Meta-Analyses Adjusted for Differences in Study Design and Quality

Background: To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen adopted. Methods: Ten studies identified in a previous systematic literature search were included. Potential sources of bias were systematically identified using bias checklists, and their impact and uncertainty were quantified using expert opinion. Study results were adjusted for biases and combined, first in a random-effects meta-analysis and then in a random-effects metaregression analysis. Results: In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95 % CI 0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I 2 = 19%). However, this naïve analysis ignores substantial differences in study quality and design. After adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95 % CI 0.17, 0.56), with no evidence of heterogeneity (I 2 = 0%). A meta-regression analysis wa