RedeR: R/Bioconductor package for representing modular structures, nested networks and multiple levels of hierarchical associations

Visualization and analysis of molecular networks are both central to systems biology. However, there still exists a large technological gap between them, especially when assessing multiple network levels or hierarchies. Here we present RedeR, an R/Bioconductor package combined with a Java core engine for representing modular networks. The functionality of RedeR is demonstrated in two different scenarios: hierarchical and modular organization in gene co-expression networks and nested structures in time-course gene expression subnetworks. Our results demonstrate RedeR as a new framework to deal with the multiple network levels that are inherent to complex biological systems. RedeR is available from http://bioconductor.org/packages/release/bioc/html/RedeR.html.     

Discovery of a novel azaindole class of antibacterial agents targeting the ATPase domains of DNA gyrase and Topoisomerase IV

We present the discovery and optimization of a novel series of bacterial topoisomerase inhibitors. Starting from a virtual screening hit, activity was optimized through a combination of structure-based design and physical property optimization. Synthesis of fewer than a dozen compounds was required to achieve inhibition of the growth of methicillin-resistant Staphyloccus aureus (MRSA) at compound concentrations of 1.56 μM. These compounds simultaneously inhibit DNA gyrase and Topoisomerase IV at similar nanomolar concentrations, reducing the likelihood of the spontaneous occurrence of target-based mutations resulting in antibiotic resistance, an increasing threat in the treatment of serious infections.     

Avoidance of roads and selection for recent cutovers by threatened caribou: fitness-rewarding or maladaptive behaviour?

The impact of anthropogenic disturbance on the fitness of prey should depend on the relative effect of human activities on different trophic levels. This verification remains rare, however, especially for large animals. We investigated the functional link between habitat selection of female caribou (Rangifer tarandus) and the survival of their calves, a fitness correlate. This top-down controlled population of the threatened forest-dwelling caribou inhabits a managed forest occupied by wolves (Canis lupus) and black bears (Ursus americanus). Sixty-one per cent of calves died from bear predation within two months following their birth. Variation in habitat selection tactics among mothers resulted in different mortality risks for their calves. When calves occupied areas with few deciduous trees, they were more likely to die from predation if the local road density was high. Although caribou are typically associated with pristine forests, females selected recent cutovers without negative impact on calf survival. This selection became detrimental, however, as regeneration took place in harvested stands owing to increased bear predation. We demonstrate that human disturbance has asymmetrical consequences on the trophic levels of a food web involving multiple large mammals, which resulted in habitat selection tactics with a greater short-term fitness payoff and, therefore, with higher evolutionary opportunity.     

Carotenoids' influence on radiotolerance of Pantoea agglomerans, a plant pathogen

Aim:  The aim of this study was to evaluate the effect of γ radiation on the carotenoid content of two strains of the Enterobacteriaceae : Pantoea agglomerans .
Methods and Results:  Pantoea agglomerans strains ATCC 49174 and RL1 were used for this study. Successive radiation treatments were performed to study the radiotolerance. Total carotenoids were obtained by multiple extraction using chloroform/methanol (2 : 1), quantified by measuring the optical density at 453 nm and their antioxidant activity measured by a colorimetric method. The D ₁₀ studies were conducted using a UC-15A irradiator loaded with ⁶⁰Co. Bacterial counts from various dilutions were carried out after irradiation. Strain ATCC 49174 irradiated at 1 kGy produced 4·3 times more carotenoids than the control, whereas carotenoid synthesis increased by 2·9-fold in the strain RL1. However, there was no significant difference in the D ₁₀ values.
Conclusion:  Carotenoid increased production is influenced by γ radiation but does not modify the tolerance to radiations.
Significance and Impact of the Study:  To our knowledge, this is the first study to demonstrate the effects of γ radiation on carotenoid production levels.     

Spiroadamantyl 1,2,4-trioxolane, 1,2,4-trioxane,and 1,2,4-trioxepane pairs: Relationship between peroxide bond iron(II) reactivity,heme alkylation efficiency,and antimalarial activity

These data suggest that iron(II) reactivity for a set of homologous spiroadamantyl 1,2,4-trioxolane, 1,2,4-trioxane, and 1,2,4-trioxepane peroxide heterocycles is a necessary, but insufficient, property of animalarial peroxides. Heme alkylation efficiency appears to give a more accurate prediction of antimalarial activity than FeSO₄-mediated reaction rates, suggesting that antimalarial activity is not merely dependent on peroxide bond cleavage, but also on the ability of reactive intermediates to alkylate heme or other proximal targets.     

Nitrogen in global animal production and management options for improving nitrogen use efficiency

Animal production systems convert plant protein into animal protein. Depending on animal species, ration and management, between 5% and 45 % of the nitrogen (N) in plant protein is converted to and deposited in animal protein. The other 55%-95% is excreted via urine and feces, and can be used as nutrient source for plant (= often animal feed) production. The estimated global amount of N voided by animals ranges between 80 and 130 Tg N per year, and is as large as or larger than the global annual N fertilizer consumption. Cattle (60%), sheep (12%) and pigs (6%) have the largest share in animal manure N production. The conversion of plant N into animal N is on average more efficient in poultry and pork production than in dairy production, which is higher than in beef and sheep production. However, differences within a type of animal production system can be as large as differences between types of animal production systems, due to large effects of the genetic potential of animals, animal feed and management. The management of animals and animal feed, together with the genetic potential of the animals, are key factors to a high efficiency of conversion of plant protein into animal protein. The efficiency of the conversion of N from animal manure, following application to land, into plant protein ranges between 0 and 60%, while the estimated global mean is about 15%. The other 40%-100% is lost to the wider environment via NH3 volatilization, denitrification, leaching and run-off in pastures or during storage and/or following application of the animal manure to land. On a global scale, only 40%-50% of the amount of N voided is collected in barns, stables and paddocks, and only half of this amount is recycled to crop land. The N losses from animal manure collected in barns, stables and paddocks depend on the animal manure management system. Relative large losses occur in confined animal feeding operations, as these often lack the land base to utilize the N from animal manure effectively. Losses will be relatively low when all manure are collected rapidly in water-tight and covered basins, and when they are subsequently applied to the land in proper amounts and at the proper time, and using the proper method (low-emission techniques). There is opportunity for improving the N conversion in animal production systems by improving the genetic production potential of the herd, the composition of the animal feed, and the management of the animal manure. Coupling of crop and animal production systems, at least at a regional scale, is one way to high N use efficiency in the whole system. Clustering of confined animal production systems with other intensive agricultural production systems on the basis of concepts from industrial ecology with manure processing is another possible way to improve N use efficiency.     

Identification of structural DNA variations in human cell cultures after long-term passage

Random amplified polymorphic DNA (RAPD) analysis was adapted for genomic identification of cell cultures and evaluation of DNA stability in cells of different origin at different culture passages. DNA stability was observed in cultures after no more than 5 passages. Adipose-derived stromal cells demonstrated increased DNA instability. RAPD fragments from different cell lines after different number of passages were cloned and sequenced. The chromosomal localization of these fragments was identified and single-nucleotide variations in RAPD fragments isolated from cell lines after 8–12 passages were revealed. Some of them had permanent localization, while most variations demonstrated random distribution and can be considered as de novo mutations.     

Limitations of Stroke Volume Estimation by Non-Invasive Blood Pressure Monitoring in Hypergravity

Background

Altitude and gravity changes during aeromedical evacuations induce exacerbated cardiovascular responses in unstable patients. Non-invasive cardiac output monitoring is difficult to perform in this environment with limited access to the patient. We evaluated the feasibility and accuracy of stroke volume estimation by finger photoplethysmography (SVp) in hypergravity.

Methods

Finger arterial blood pressure (ABP) waveforms were recorded continuously in ten healthy subjects before, during and after exposure to +Gz accelerations in a human centrifuge. The protocol consisted of a 2-min and 8-min exposure up to +4 Gz. SVp was computed from ABP using Liljestrand, systolic area, and Windkessel algorithms, and compared with reference values measured by echocardiography (SVe) before and after the centrifuge runs.

Results

The ABP signal could be used in 83.3% of cases. After calibration with echocardiography, SVp changes did not differ from SVe and values were linearly correlated (p<0.001). The three algorithms gave comparable SVp. Reproducibility between SVp and SVe was the best with the systolic area algorithm (limits of agreement −20.5 and +38.3 ml).

Conclusions

Non-invasive ABP photoplethysmographic monitoring is an interesting technique to estimate relative stroke volume changes in moderate and sustained hypergravity. This method may aid physicians for aeronautic patient monitoring.     

Situation of mycotoxins in milk, dairy products and human milk in Egypt

Abstact  Milk and dairy products purchased at Egyptian markets and breast milk from lactating mothers in Cairo and Giza governorates were analyzed for some mycotoxins. Three of 15 cows’ milk samples were found positive for Afl. M₁ with mean value 6.3 ppb. Only one sample of dried milk was positive (5 ppb). Two of 10 hard cheese samples contained detectable levels of Afl. M₁ (3and 6 ppb), whereas one sample containing Afl. B₁ and G₁ (10 and 4 ppb resp.). For soft cheese one sample of 10 was positive for Afl. M₁ (0.5 ppb). Blue veined cheeses were free of Afl. M₁ and PR-toxins. For breast milk two of 10 samples were positive for Afl. M₁ (20%) with mean value 2.75 ppb, while 3 of 10 samples were positive for Ochratoxin A (30 %).