The structure of Acidithiobacillus ferrooxidans c(4)-cytochrome: a model for complex-induced electron transfer tuning

The study of electron transfer between the copper protein rusticyanin (RCy) and the c(4)-cytochrome CYC(41) of the acidophilic bacterium Acidithiobacillus ferrooxidans has evidenced a remarkable decrease of RCy's redox potential upon complex formation. The structure of the CYC(41) obtained at 2.2 A resolution highlighted a specific glutamate residue (E121) involved in zinc binding as potentially playing a central role in this effect, required for the electron transfer to occur. EPR and stopped-flow experiments confirmed the strong inhibitory effect of divalent cations on CYC(41):RCy complex formation. A docking analysis of the CYC(41) and RCy structure allows us to propose a detailed model for the complex-induced tuning of electron transfer in agreement with our experimental data, which could be representative of other copper proteins involved in electron transfer.     

DNA Methylation Signatures Triggered by Prenatal Maternal Stress Exposure to a Natural Disaster: Project Ice Storm

Background

Prenatal maternal stress (PNMS) predicts a wide variety of behavioral and physical outcomes in the offspring. Although epigenetic processes may be responsible for PNMS effects, human research is hampered by the lack of experimental methods that parallel controlled animal studies. Disasters, however, provide natural experiments that can provide models of prenatal stress.

Methods

Five months after the 1998 Quebec ice storm we recruited women who had been pregnant during the disaster and assessed their degrees of objective hardship and subjective distress. Thirteen years later, we investigated DNA methylation profiling in T cells obtained from 36 of the children, and compared selected results with those from saliva samples obtained from the same children at age 8.

Results

Prenatal maternal objective hardship was correlated with DNA methylation levels in 1675 CGs affiliated with 957 genes predominantly related to immune function; maternal subjective distress was uncorrelated. DNA methylation changes in SCG5 and LTA, both highly correlated with maternal objective stress, were comparable in T cells, peripheral blood mononuclear cells (PBMCs) and saliva cells.

Conclusions

These data provide first evidence in humans supporting the conclusion that PNMS results in a lasting, broad, and functionally organized DNA methylation signature in several tissues in offspring. By using a natural disaster model, we can infer that the epigenetic effects found in Project Ice Storm are due to objective levels of hardship experienced by the pregnant woman rather than to her level of sustained distress.     

Microchemical imaging of iodine distribution in the brown alga Laminaria digitata suggests a new mechanism for its accumulation

Brown algal kelp species are the most efficient iodine accumulators among all living systems, with an average content of 1.0% of dry weight in Laminaria digitata. The iodine distributions in stipe and blade sections from L. digitata were investigated at tissue and subcellular levels. The quantitative tissue mapping of iodine and other trace elements (Cl, K, Ca, Fe, Zn, As and Br) was provided by the proton microprobe with spatial resolutions down to 2 μm. Chemical imaging at a subcellular resolution (below 100 nm) was performed using the secondary ion mass spectrometry microprobe. Sets of samples were prepared by both chemical fixation and cryofixation procedures. The latter prevented the diffusion and the leaching of labile inorganic iodine species, which were estimated at around 95% of the total content by neutron activation analysis. The distribution of iodine clearly shows a huge, decreasing gradient from the meristoderm to the medulla. The contents of iodine reach very high levels in the more external cell layers, up to 191 ± 5 mg g⁻¹ of dry weight in stipe sections. The peripheral tissue is consequently the main storage compartment of iodine. At the subcellular level, iodine is mainly stored in the apoplasm and not in an intracellular compartment as previously proposed. This unexpected distribution may provide an abundant and accessible source of labile iodine species which can be easily remobilized for potential chemical defense and antioxidative activities. According to these imaging data, we proposed new hypotheses for the mechanism of iodine storage in L. digitata tissues. In memory of Dr. Charles Mioskowski, “Miko,” who died on 2 June 2007.     

Stabilization of the integrase‐DNA complex by Mg2+ ions and prediction of key residues for binding HIV‐1 integrase inhibitors

The HIV‐1 integrase is an attractive target for the therapeutics development against AIDS, as no host homologue of this protein has been identified. The integrase strand transfer inhibitors (INSTIs), including raltegravir, specifically target the second catalytic step of the integration process by binding to the DDE motif of the catalytic site and coordinating Mg²⁺ ions. Recent X‐ray crystallographic structures of the integrase/DNA complex from prototype foamy virus allowed to investigate the role of the different partners (integrase, DNA, Mg²⁺ ions, raltegravir) in the complex stability using molecular dynamics (MD) simulations. The presence of Mg²⁺ ions is found to be essential for the stability, whereas the simultaneous presence of raltegravir and Mg²⁺ ions has a destabilizing influence. A homology model of HIV‐1 integrase was built on the basis of the X‐ray crystallographic information, and protein marker residues for the ligand binding were detected by clustering the docking poses of known HIV‐1 integrase inhibitors on the model. Interestingly, we had already identified some of these residues to be involved in HIV‐1 resistance mutations and in the stabilization of the catalytic site during the MD simulations. Classification of protein conformations along MD simulations, as well as of ligand docking poses, was performed by using an original learning method, based on self‐organizing maps. This allows us to perform a more in‐depth investigation of the free‐energy basins populated by the complex in MD simulations on the one hand, and a straightforward classification of ligands according to their binding residues on the other hand. Proteins 2014; 82:466–478. © 2013 Wiley Periodicals, Inc.     

Potential Risk of Regional Disease Spread in West Africa through Cross-Border Cattle Trade

Background

Transboundary animal movements facilitate the spread of pathogens across large distances. Cross-border cattle trade is of economic and cultural importance in West Africa. This study explores the potential disease risk resulting from large-scale, cross-border cattle trade between Togo, Burkina Faso, Ghana, Benin, and Nigeria for the first time.

Methods and Principal Findings

A questionnaire-based survey of livestock movements of 226 cattle traders was conducted in the 9 biggest cattle markets of northern Togo in February-March 2012. More than half of the traders (53.5%) operated in at least one other country. Animal flows were stochastically simulated based on reported movements and the risk of regional disease spread assessed. More than three quarters (79.2%, range: 78.1–80.0%) of cattle flowing into the market system originated from other countries. Through the cattle market system of northern Togo, non-neighbouring countries were connected via potential routes for disease spread. Even for diseases with low transmissibility and low prevalence in a given country, there was a high risk of disease introduction into other countries.

Conclusions

By stochastically simulating data collected by interviewing cattle traders in northern Togo, this study identifies potential risks for regional disease spread in West Africa through cross-border cattle trade. The findings highlight that surveillance for emerging infectious diseases as well as control activities targeting endemic diseases in West Africa are likely to be ineffective if only conducted at a national level. A regional approach to disease surveillance, prevention and control is essential.     

Genome-wide interval mapping using SNPs identifies new QTL for growth,body composition and several physiological variables in an F2 intercross between fat and lean chicken lines

Background

For decades, genetic improvement based on measuring growth and body composition traits has been successfully applied in the production of meat-type chickens. However, this conventional approach is hindered by antagonistic genetic correlations between some traits and the high cost of measuring body composition traits. Marker-assisted selection should overcome these problems by selecting loci that have effects on either one trait only or on more than one trait but with a favorable genetic correlation. In the present study, identification of such loci was done by genotyping an F₂ intercross between fat and lean lines divergently selected for abdominal fatness genotyped with a medium-density genetic map (120 microsatellites and 1302 single nucleotide polymorphisms). Genome scan linkage analyses were performed for growth (body weight at 1, 3, 5, and 7 weeks, and shank length and diameter at 9 weeks), body composition at 9 weeks (abdominal fat weight and percentage, breast muscle weight and percentage, and thigh weight and percentage), and for several physiological measurements at 7 weeks in the fasting state, i.e. body temperature and plasma levels of IGF-I, NEFA and glucose. Interval mapping analyses were performed with the QTLMap software, including single-trait analyses with single and multiple QTL on the same chromosome.

Results

Sixty-seven QTL were detected, most of which had never been described before. Of these 67 QTL, 47 were detected by single-QTL analyses and 20 by multiple-QTL analyses, which underlines the importance of using different statistical models. Close analysis of the genes located in the defined intervals identified several relevant functional candidates, such as ACACA for abdominal fatness, GHSR and GAS1 for breast muscle weight, DCRX and ASPSCR1 for plasma glucose content, and ChEBP for shank diameter.

Conclusions

The medium-density genetic map enabled us to genotype new regions of the chicken genome (including micro-chromosomes) that influenced the traits investigated. With this marker density, confidence intervals were sufficiently small (14 cM on average) to search for candidate genes. Altogether, this new information provides a valuable starting point for the identification of causative genes responsible for important QTL controlling growth, body composition and metabolic traits in the broiler chicken.     

The Spread of Aedes albopictus in Metropolitan France: Contribution of Environmental Drivers and Human Activities and Predictions for a Near Future

Invasion of new territories by insect vector species that can transmit pathogens is one of the most important threats for human health. The spread of the mosquito Aedes albopictus in Europe is emblematic, because of its major role in the emergence and transmission of arboviruses such as dengue or chikungunya. Here, we modeled the spread of this mosquito species in France through a statistical framework taking advantage of a long-term surveillance dataset going back to the first observation of Ae. albopictus in the Metropolitan area. After validating the model, we show that human activities are especially important for mosquito dispersion while land use is a major factor for mosquito establishment. More importantly, we show that Ae. albopictus invasion is accelerating through time in this area, resulting in a geographic range extending further and further year after year. We also show that sporadic “jump” of Ae. albopictus in a new location far from the colonized area did not succeed in starting a new invasion front so far. Finally, we discuss on a potential adaptation to cooler climate and the risk of invasion into Northern latitudes.     

Preparation and pharmacological profile of 7-(alpha-azolylbenzyl)-1H-indoles and indolines as new aromatase inhibitors

Aromatase (P450 arom) is a target of pharmacological interest for the treatment of breast cancer. New series of 7-(alpha-azolylbenzyl)-1H-indoles and indolines were synthesized as non-steroidal inhibitors of P450 arom. Selectivity was studied towards P450 17alpha enzyme. The most active compound, 1-ethyl-7-[(imidazol-1-yl)(4-chlorophenyl)methyl]-1H-indole 12c exhibited promising relative potency (rp) of 336 (rp of aminoglutethimide=1) and most of the described azoles were active and selective towards P450 arom.     

Proteomics application exercise of the Swiss Proteomics Society: report of the SPS'02 session

After the success of the mass spectrometry (MS) round table that was held at the first Swiss Proteomics Society congress (SPS'01) in Geneva, the SPS has organized a proteomics application exercise and allocated a full session at the SPS'02 congress. The main objective was to encourage the exchange of expertise in protein identification, with a focus on the use of mass spectrometry, and to create a bridge between the users' questions and the instrument providers' solutions. Two samples were sent to fifteen interested labs, including academic groups and MS hardware providers. Participants were asked to identify and partially characterize the samples. They consisted of a complex mixture of peptide/proteins (sample A) and an almost pure recombinant peptide carrying post-translational modifications (sample B). Sample A was an extract of snake venom from the species Bothrops jararaca. Sample B was a recombinant and modified peptide derived from the shrimp Penaeus vannamei penaeidin 3a. The eight labs that returned results reported the use of a wide range of MS instrumentation and techniques. They mentioned a variety of time and manpower allocations. The origin of sample A was generally identified together with a number of database protein entries. The difficulty of the sample identification lay in the incomplete knowledge of the Bothrops species genome sequence and is discussed. Sample B was generally and correctly identified as penaeidin. However, only one group reported the full primary structure. Interestingly, the approaches were again varied and are discussed in the text.