EPR and pulsed ENDOR study of intermediates from reactions of aromatic azides with group 13 metal trichlorides

The reactions of group 13 metal trichlorides with aromatic azides were examined by CW EPR and pulsed ENDOR spectroscopies. Complex EPR spectra were obtained from reactions of aluminium, gallium and indium trichlorides with phenyl azides containing a variety of substituents. Analysis of the spectra showed that 4-methoxy-, 3-methoxy- and 2-methoxyphenyl azides all gave ‘dimer’ radical cations [ArNHC6H4NH2]+• and trimers [ArNHC6H4NHC6H4NH2]+• followed by polymers. 4-Azidobenzonitrile, with its electron-withdrawing substituent, did not react. In general the aromatic azides appeared to react most rapidly with AlCl3 but this reagent tended to generate much polymer. InCl3 was the least reactive group 13 halide. DFT computations of the radical cations provided corroborating evidence and suggested that the unpaired electrons were accommodated in extensive π-delocalised orbitals. A mechanism to account for the reductive conversion of aromatic azides to the corresponding anilines and thence to the dimers and trimers is proposedPublisher PDFPeer reviewe

Multi-Criteria Decision Analysis as an Innovative Approach to Managing Zoonoses: Results from a Study on Lyme Disease in Canada

ackground: Zoonoses are a growing international threat interacting at the human-animal-environment interface and call for transdisciplinary and multi-sectoral approaches in order to achieve effective disease management. The recent emergence of Lyme disease in Quebec, Canada is a good example of a complex health issue for which the public health sector must find protective interventions. Traditional preventive and control interventions can have important environmental, social and economic impacts and as a result, decision-making requires a systems approach capable of integrating these multiple aspects of interventions. This paper presents the results from a study of a multi-criteria decision analysis (MCDA) approach for the management of Lyme disease in Quebec, Canada. MCDA methods allow a comparison of interventions or alternatives based on multiple criteria. Methods: MCDA models were developed to assess various prevention and control decision criteria pertinent to a comprehensive management of Lyme disease: a first model was developed for surveillance interventions and a second was developed for control interventions. Multi-criteria analyses were conducted under two epidemiological scenarios: a disease emergence scenario and an epidemic scenario. Results: In general, we observed a good level of agreement between stakeholders. For the surveillance model, the three preferred interventions were: active surveillance of vectors by flagging or dragging, active surveillance of vectors by trapping of small rodents and passive surveillance of vectors of human origin. For the control interventions model, basic preventive communications, human vaccination and small scale landscaping were the three preferred interventions. Scenarios were found to only have a small effect on the group ranking of interventions in the control model. Conclusions: MCDA was used to structure key decision criteria and capture the complexity of Lyme disease management. This facilitated the identification of gaps in the scientific literature and enabled a clear identification of complementary interventions that could be used to improve the relevance and acceptability of proposed prevention and control strategy. Overall, MCDA presents itself as an interesting systematic approach for public health planning and zoonoses management with a “One Health” perspective

Voltage Sensor Probes (VSPs) as an Efficient Tool to Screen for Inhibitors of Voltage-Gated Sodium Channels

Voltage-gated sodium channels (Nav) represent a therapeutically validated group of targets for the development of antiepileptic drugs, analgesics and antiarrhythmics [1]. However most of the existing drugs acting as Nav blockers suffer from multiple side effects, but the existence of a multigene family of Nav [2] suggests that the identification of new compounds that selectively block Nav isoforms might have better therapeutic efficiency and reduced side effects. Due to their molecular interference with numerous ion channels, alkaloids represent a group of natural products of particular interest. This is the reason why we have evaluated the efficiency of an in-house method to screen a library of isoquinoline alkaloids formerly isolated in our laboratory. Mammalian GH3 cells constitutively expressing Nav where used in conjunction with Voltage Sensor Probes (VSPs), the signals being read on a fluorescence plate reader. Thanks to this technique, we were able to precisely detect Nav channels activators or blockers. Among 62 compounds tested, 5 isoquinolines appeared as potent Nav channels inhibitors. References: 1. Salat, K. et al. (2014) EOID 23:1093-1104 2. Yu, F.H. et al (2003) Genome Biol. 4

Grief experiences among female American and Arab undergraduate college students

© 2015 The Author(s). The purpose of this study was to compare the incidence of grief among American and Arab female undergraduate students, the effects of their grief, and risk of prolonged grief disorder. A total of 471 female undergraduate students, 308 (65.4%) from the United Arab Emirates and 163 (34.6%) from the United States, completed a survey about their grief experiences. Students experiencing a significant loss also completed the Prolonged Grief Disorder Questionnaire. Findings revealed that overall approximately 38.4% (n=181) of all 471 students experienced the loss of a significant person in their lives within the past 24 months; a similar percentage was found in each sub group. Students reported various grief effects with American students experiencing more effects related to sleep, relationships, academics, physical well-being, religion/spirituality, and outlook on life than Arab students. Only a small number (10, 5.52%) of students met the criteria for prolonged grief disorder; however, most students were female Arab students. Limitations of the study and recommendations for future research are provided

Water Use and Yield of Millet Under the Zai System: Understanding the Processes Using Simulation

In the drylands of Africa about 90% of the population is rural and depends on subsistence agriculture for their livelihoods. There is an increasing pressure on the natural resources due to the high population growth, and farmers are constrained to cultivate marginal lands, thereby compounding the land degradation problem. Low and erratic rainfall, its poor distribution within the growing season, prolonged dry spells, lack of adequate water supply due to soil physical degradation (soil crusting) and nutrient shortage adversely affect crop growth and yields. To address these problems, indigenous, easy to implement innovations such as the zai system may provide solutions to increase productivity. The effect of three planting techniques (Flat, zai pit of 25 cm and zai pit of 50 cm diameter) and three fertility management options (control, crop residue, cattle manure) were tested at Damari in 1999 in Niger. Soil water was monitored from weekly measurements using a Didcot Wallingford neutron probe throughout the growing period. Data from that experiment were used to determine if the CERES-Millet model of the Decision Support System for Agrotechnology Transfer (DSSAT) is sufficiently robust to predict yield response to the zai water harvesting system. The model simulated the observed yield response of the control and the manure-amended plots with high r-square (0.99), low residual mean error square (340 kg·ha−1 for above ground biomass and 94 kg·ha−1 for grain yield) and high d-statistic (0.99), but this was not the case for the crop residue treatment, which was over-predicted. Soil water content and extractable soil water were also well simulated for the control and manure treatments. This evaluation of DSSAT provides a starting point for research to evaluate the performance of these technologies over wider areas in West Africa. The application of models for such studies must be interpreted in the context of limitations of the model to address some constraints. Nevertheless, the highly variable crop responses due to interacting effects of rainfall, management and adverse soil conditions in this region make this an extremely important approach in planning for technology ­adoption in an area and in interpreting results from experimental field researc

Analysis of the Intrinsically Disordered N-Terminus of the DNA Junction-Resolving Enzyme T7 Endonuclease I:Identification of Structure Formed upon DNA Binding

This work was supported by grants from The Engineering and Physical Sciences Research Council (EPSRC), Basic Technology EP/F039034/1, The Wellcome Trust, 099149/Z/12/Z, and Cancer Research UK (CRUK), C28/A18604.The four-way (Holliday) DNA junction of homologous recombination is processed by the symmetrical cleavage of two strands by a nuclease. These junction-resolving enzymes bind to four-way junctions in dimeric form, distorting the structure of the junction in the process. Crystal structures of T7 endonuclease I have been determined as free protein, and the complex with a DNA junction. In neither crystal structure was the N-terminal 16-amino acid peptide visible, yet deletion of this peptide has a marked effect on the resolution process. Here we have investigated the N-terminal peptide by inclusion of spin-label probes at unique sites within this region, studied by electron paramagnetic resonance. Continuous wave experiments show that these labels are mobile in the free protein but become constrained on binding a DNA junction, with the main interaction occurring for residues 7-10 and 12. Distance measurements between equivalent positions within the two peptides of a dimer using PELDOR showed that the intermonomeric distances for residues 2-12 are long and broadly distributed in the free protein but are significantly shortened and become more defined on binding to DNA. These results suggest that the N-terminal peptides become more organized on binding to the DNA junction and nestle into the minor grooves at the branchpoint, consistent with the biochemical data indicating an important role in the resolution process. This study demonstrates the presence of structure within a protein region that cannot be viewed by crystallography.Publisher PDFPeer reviewe

Abiotic Stresses Tolerance and Nutrients Contents in Groundnut, Pearl Millet and Sorghum Mini Core Germplasm for Food and Nutrition Security

Groundnut, pearl millet and sorghum germplasm were investigated to identify new sources of tolerance to low phosphorus (LP) and/or drought stress (WS) and to assess genotypic variation for iron (Fe) and zinc (Zn) contents. Experiments were conducted in lysimetre conditions in a randomized completely block design with 5 replications, 2 water and 2 phosphorus treatments. Genotypic variability was observed for morphoagronomic and nutrients traits investigated. Groundnut accessions ICG 3312, ICG 11855, ICG 10053, ICG 15232 and ICG 11088 revealed drought tolerant. The combined WS-LP effect (73%) was higher than individual WS (68%) and LP (49%) effects. LP signifi cantly delayed heading and fl owering dates, accessions IP1060, IP11405 and IP9000 (millet), and ISS1412, ISS2167, ISS376 and ISS738 (sorghum) showed less delay and LP tolerance. Fe and Zn contents under LP showed that accessions IP17775, IP5581, IP5153, IP1060, IP6517 and IP5438 of millet; ISS376, ISS1412, ISS2167, ISS242, ISS311 and ISS2151 of sorghum revealed high Fe and/or Zn concentrations

The intensification of thermal extremes in west Africa

International audienceThis study aims in filling the gap in understanding the relationship between trend and extreme in diurnal and nocturnal temperatures (Tx and Tn) over the Gulf of Guinea area and the Sahel. Time-evolution and trend of Tx and Tn anomalies, extreme temperatures and heat waves are examined using regional and station-based indices over the 1900–2012 and 1950–2012 periods respectively. In investigating extreme temperature anomalies and heat waves, a percentile method is used. At the regional and local scales, rising trends in Tx and Tn anomalies, which appear more pronounced over the past 60 years, are identified over the two regions. The trends are characterized by an intensification of: i) nocturnal/Tn warming over the second half of the 20th century; and ii) diurnal/Tx warming over the post-1980s. This is the same scheme with extreme warm days and warm nights. Finally annual number of diurnal and nocturnal heat waves has increase over the Gulf of Guinea coastal regions over the second half of the 20th century, and even more substantially over the post-1980s period. Although this trend in extreme warm days and nights is always overestimated in the simulations, from the Coupled Model Intercomparison Project Phase 5 (CMIP5), those models display rising trends whatever the scenario, which are likely to be more and more pronounced over the two regions in the next 50 years

Voltage Sensor Probes as an efficient tool to screen for new modulators of voltage-gated sodium channels

Voltage-gated sodium channels (Nav) constitute the molecular targets of clinically used drugs for treatments of various diseases (epilepsies, chronic pain, cardiac arrythmies…) and also of numerous toxins from animals and plants. The development of useful screening assay for the discovery of new ligands in/ from chemicals libraries or animal venoms and either plant extract still represents a challenge of great interest. Here, we used a mammalian GH3 cells that constitutively express at least three different brain Nav channels isoforms (Nav1.1, Nav1.2, Nav1.3 and Nav1.6) in order to identify in a library of in-house natural alkaloids, novel compounds of therapeutical interest. For this screening, we developed a method based on the use of Voltage Sensor Probes (VSPs) that we adapted to detect both activators and blockers of Nav channels. Among 62 compounds tested, 5 isoquinolines appeared as potent Nav channels inhibitors. Other compounds were characterized as specific gating modifier of Nav channels. While most of these alkaloids have been already described in the literature, their abilities to act on Nav channels were unknown. In conclusion, we demonstrated the potency of this novel screening method using VSPs to identify novel ligands of Nav channels of therapeutical interests. References: 1. Salat, K. et al. (2014) EOID 23:1093-1104 2. Yu, F.H. et al (2003) Genome Biol. 4