Epidemiology, Species Distribution, Antifungal Susceptibility and Outcome of Nosocomial Candidemia in a Tertiary Care Hospital in Italy

Candida is an important cause of bloodstream infections (BSI), causing significant mortality and morbidity in health care settings. From January 2008 to December 2010 all consecutive patients who developed candidemia at San Martino University Hospital, Italy were enrolled in the study. A total of 348 episodes of candidaemia were identified during the study period (January 2008–December 2010), with an incidence of 1,73 episodes/1000 admissions. Globally, albicans and non-albicans species caused around 50% of the cases each. Non-albicans included Candida parapsilosis (28.4%), Candida glabrata (9.5%), Candida tropicalis (6.6%), and Candida krusei (2.6%). Out of 324 evaluable patients, 141 (43.5%) died within 30 days from the onset of candidemia. C. parapsilosis candidemia was associated with the lowest mortality rate (36.2%). In contrast, patients with C. krusei BSI had the highest mortality rate (55.5%) in this cohort. Regarding the crude mortality in the different units, patients in Internal Medicine wards had the highest mortality rate (54.1%), followed by patients in ICU and Hemato-Oncology wards (47.6%)

Trade-offs and Noise Tolerance in Signal Detection by Genetic Circuits

Genetic circuits can implement elaborated tasks of amplitude or frequency signal detection. What type of constraints could circuits experience in the performance of these tasks, and how are they affected by molecular noise? Here, we consider a simple detection process–a signal acting on a two-component module–to analyze these issues. We show that the presence of a feedback interaction in the detection module imposes a trade-off on amplitude and frequency detection, whose intensity depends on feedback strength. A direct interaction between the signal and the output species, in a type of feed-forward loop architecture, greatly modifies these trade-offs. Indeed, we observe that coherent feed-forward loops can act simultaneously as good frequency and amplitude noise-tolerant detectors. Alternatively, incoherent feed-forward loop structures can work as high-pass filters improving high frequency detection, and reaching noise tolerance by means of noise filtering. Analysis of experimental data from several specific coherent and incoherent feed-forward loops shows that these properties can be realized in a natural context. Overall, our results emphasize the limits imposed by circuit structure on its characteristic stimulus response, the functional plasticity of coherent feed-forward loops, and the seemingly paradoxical advantage of improving signal detection with noisy circuit components

(Q)SAR Modelling of Nanomaterial Toxicity - A Critical Review

There is an increasing recognition that nanomaterials pose a risk to human health, and that the novel engineered nanomaterials (ENMs) in the nanotechnology industry and their increasing industrial usage poses the most immediate problem for hazard assessment, as many of them remain untested. The large number of materials and their variants (different sizes and coatings for instance) that require testing and ethical pressure towards non-animal testing means that expensive animal bioassay is precluded, and the use of (quantitative) structure activity relationships ((Q)SAR) models as an alternative source of hazard information should be explored. (Q)SAR modelling can be applied to fill the critical knowledge gaps by making the best use of existing data, prioritize physicochemical parameters driving toxicity, and provide practical solutions to the risk assessment problems caused by the diversity of ENMs. This paper covers the core components required for successful application of (Q)SAR technologies to ENMs toxicity prediction, and summarizes the published nano-(Q)SAR studies and outlines the challenges ahead for nano-(Q)SAR modelling. It provides a critical review of (1) the present status of the availability of ENMs characterization/toxicity data, (2) the characterization of nanostructures that meets the need of (Q)SAR analysis, (3) the summary of published nano-(Q)SAR studies and their limitations, (4) the in silico tools for (Q)SAR screening of nanotoxicity and (5) the prospective directions for the development of nano-(Q)SAR models

A point mutation in the Nul gene of bacteriophage λ facilitates phage growth in Escherichia coli with himA and gyrB mutations

A mutant of λ was isolated that grows in the Escherichia coli himAΔ/gyrB-him320 (Ts) double mutant at 42°C; conditions which are non-permissive for wild-type λ growth. The responsible mutation, ohm1 , alters the 40th codon of the Nul reading frame. The Nul and A gene products comprise the terminase protein which cleaves concatameric DNA into unit-length phage genomes during DNA packaging. The Nul-ohm1 gene product acts in trans to support λ growth in the double himA/gyrB mutant, and λ cos154 growth in the single himA mutant. The observation that an alteration in Nul suppresses the inhibition of growth in the double himA/gyrB mutant implicates DNA gyrase, as well as integration host factor, in the DNA: protein interactions that occur at the initiation of packaging.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47567/1/438_2004_Article_BF00322458.pd

Synergistic transcription activation: a dual role for CRP in the activation of an Escherichia coli promoter depending on MalT and CRP

Activation of the Escherichia coli malEp promoter relies on the formation of a higher order structure involving cooperative binding of MalT to promoter-proximal and promoter-distal sites as well as CRP binding to three sites located in between. MalT is the primary activator and one function of CRP is to facilitate cooperative binding of MalT to its cognate sites by bending the intervening DNA. It is shown here that CRP also participates directly in malEp activation. This function is carried out by the molecule of CRP bound to the CRP site centered at –139.5 (CRP site 3). This molecule of CRP recruits RNA polymerase by promoting the binding of the RNA polymerase α subunit C-terminal domain (αCTD) to DNA immediately downstream from CRP site 3, via a contact between αCTD and activating region I of CRP. The action of MalT and CRP at malEp hence provides the example of a novel and complex mechanism for transcriptional synergy in prokaryotes whereby one activator both helps the primary activator to form a productive complex with promoter DNA and interacts directly with RNA polymerase holoenzyme