Transcriptional downregulation of agr expression in Staphylococcus aureus during growth in human serum can be overcome by constitutively active mutant forms of the sensor kinase AgrC

The temporal and cell density-dependent regulation of expression of virtually all the Staphylococcus aureus virulon is under the control of the agr (accessory gene regulatory) operon. The expression of the agr operon is subject to transcriptional regulation by the AgrA/C two-component response regulator/sensor kinase pair. During bacteraemia, a frequent syndrome caused by methicillin-resistant S. aureus (MRSA), the transcriptional downregulation of agr expression has been attributed to the sequestration of the quorum-signalling molecule auto-inducing peptide (AIP) by the human serum component apolipoprotein B as part of an innate immune response to infection. However, it is not known whether transcriptional downregulation of agr expression during growth in human serum is additionally subjected to regulation by transcription regulatory proteins that either directly or indirectly affect transcription from the agr operon promoters. Here, using chromosomal fluorescence reporters of agr expression in S. aureus, we show that the transcriptional downregulation of agr expression in human serum can be overcome using constitutive active mutant forms of AgrC. Therefore, it seems that the sequestration of the AIP is likely to be the only mechanism by which the host innate immune response limits agr expression at the transcriptional level to maintain the host–pathogen balance towards a noninvasive outcome

Targeted treatment of recurrent platinum-resistant ovarian cancer: Current and emerging therapies

With advances in surgical techniques and chemotherapeutic agents, mortality rates from epithelial ovarian cancer (EOC) have slightly decreased over the last 30 years. However, EOC still ranks as the most deadly gynecologic cancer with an overall 5-year survival rate of 45%. Prognosis is especially disappointing for women with platinum-resistant disease, where 80% of patients will fail to respond to available therapies. Emerging treatment strategies have subsequently focused on targets which are integral to tumor growth and metastasis. In this review, we will focus on those innovative agents currently under investigation in clinical trials. © 2011 Mantia-Smaldone et al, publisher and licensee Dove Medical Press Ltd

Adaptive Lévy processes and area-restricted search in human foraging

A considerable amount of research has claimed that animals’ foraging behaviors display movement lengths with power-law distributed tails, characteristic of Lévy flights and Lévy walks. Though these claims have recently come into question, the proposal that many animals forage using Lévy processes nonetheless remains. A Lévy process does not consider when or where resources are encountered, and samples movement lengths independently of past experience. However, Lévy processes too have come into question based on the observation that in patchy resource environments resource-sensitive foraging strategies, like area-restricted search, perform better than Lévy flights yet can still generate heavy-tailed distributions of movement lengths. To investigate these questions further, we tracked humans as they searched for hidden resources in an open-field virtual environment, with either patchy or dispersed resource distributions. Supporting previous research, for both conditions logarithmic binning methods were consistent with Lévy flights and rank-frequency methods–comparing alternative distributions using maximum likelihood methods–showed the strongest support for bounded power-law distributions (truncated Lévy flights). However, goodness-of-fit tests found that even bounded power-law distributions only accurately characterized movement behavior for 4 (out of 32) participants. Moreover, paths in the patchy environment (but not the dispersed environment) showed a transition to intensive search following resource encounters, characteristic of area-restricted search. Transferring paths between environments revealed that paths generated in the patchy environment were adapted to that environment. Our results suggest that though power-law distributions do not accurately reflect human search, Lévy processes may still describe movement in dispersed environments, but not in patchy environments–where search was area-restricted. Furthermore, our results indicate that search strategies cannot be inferred without knowing how organisms respond to resources–as both patched and dispersed conditions led to similar Lévy-like movement distributions

Successional changes of epibiont fouling communities of the cultivated kelp Alaria esculenta: predictability and influences

There has been an increase in commercial-scale kelp cultivation in Europe, with fouling of cultivated kelp fronds presenting a major challenge to the growth and development of the industry. The presence of epibionts decreases productivity and impacts the commercial value of the crop. Several abiotic and biotic factors may influence the occurrence and degree of fouling of wild and cultivated fronds. Using a commercial kelp farm on the SW coast of Ireland, we studied the development of fouling communities on cultivated Alaria esculenta fronds over 2 typical growing seasons. The predictability of community development was assessed by comparing mean occurrence-day. Hypotheses that depth, kelp biomass, position within the farm and the hydrodynamic environment affect the fouling communities were tested using species richness and community composition. Artificial kelp mimics were used to test whether local frond density could affect the fouling communities. Species richness increased over time during both years, and species composition was consistent over years with early successional communities converging into later communities (no significant differences between June 2014 and June 2015 communities, ANOSIM; R = -0.184, p > 0.05). The timing of species occurrences was predictable across years for all shared species. Variations in biomass, depth and position within the farm had no significant effect on species richness and composition. Results from artificial kelp mimics suggest possible hydrodynamic effects. The ability to understand succession and the timing of occurrences of fouling organisms and predict their arrival has significant benefits for the seaweed cultivation industry

Cranial functional (psychogenic) movement disorders

Functional (psychogenic) neurological symptoms are frequently encountered in neurological practice. Cranial movement disorders—affecting the eyes, face, jaw, tongue, or palate—are an under-recognised feature of patients with functional symptoms. They can present in isolation or in the context of other functional symptoms; in particular, for functional eye movements, positive clinical signs such as convergence spasms can be triggered by the clinical examination. Although the specialty of functional neurological disorders has expanded, appreciation of cranial functional movement disorders is still insufficient. Identification of the positive features of cranial functional movement disorders such as convergence and unilateral platysmal spasm might lend diagnostic weight to a suspected functional neurological disorder. Understanding of the differential diagnosis, which is broad and includes many organic causes (eg, stroke), is essential to make an early and accurate diagnosis to prevent complications and initiate appropriate management. Increased understanding of these disorders is also crucial to drive clinical trials and studies of individually tailored therapies

Modelling complex systems of heterogeneous agents to better design sustainability transitions policy

This article proposes a fundamental methodological shift in the modelling of policy interventions for sustainability transitions in order to account for complexity (e.g. self-reinforcing mechanisms, such as technology lock-ins, arising from multi-agent interactions) and agent heterogeneity (e.g. differences in consumer and investment behaviour arising from income stratification). We first characterise the uncertainty faced by climate policy-makers and its implications for investment decision-makers. We then identify five shortcomings in the equilibrium and optimisation-based approaches most frequently used to inform sustainability policy: (i) their normative, optimisation-based nature, (ii) their unrealistic reliance on the full-rationality of agents, (iii) their inability to account for mutual influences among agents (multi-agent interactions) and capture related self-reinforcing (positive feedback) processes, (iv) their inability to represent multiple solutions and path-dependency, and (v) their inability to properly account for agent heterogeneity. The aim of this article is to introduce an alternative modelling approach based on complexity dynamics and agent heterogeneity, and explore its use in four key areas of sustainability policy, namely (1) technology adoption and diffusion, (2) macroeconomic impacts of low-carbon policies, (3) interactions between the socio-economic system and the natural environment, and (4) the anticipation of policy outcomes. The practical relevance of the proposed methodology is subsequently discussed by reference to four specific applications relating to each of the above areas: the diffusion of transport technology, the impact of low-carbon investment on income and employment, the management of cascading uncertainties, and the cross-sectoral impact of biofuels policies. In conclusion, the article calls for a fundamental methodological shift aligning the modelling of the socio-economic system with that of the climatic system, for a combined and realistic understanding of the impact of sustainability policies.J.-F. M. acknowledge the UK Engineering and Physical Sciences Research Council (EPSRC), fellowship no EP/ K007254/1 and J.-F.M. and J. V. acknowledge a networking grant of the EPSRC (Newton Fund) EP/N002504/1.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.gloenvcha.2016.02.00

Constructing a Stochastic Model of Bumblebee Flights from Experimental Data

PMCID: PMC3592844This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Characterization of growth and metabolism of the haloalkaliphile Natronomonas pharaonis

Natronomonas pharaonis is an archaeon adapted to two extreme conditions: high salt concentration and alkaline pH. It has become one of the model organisms for the study of extremophilic life. Here, we present a genome-scale, manually curated metabolic reconstruction for the microorganism. The reconstruction itself represents a knowledge base of the haloalkaliphile's metabolism and, as such, would greatly assist further investigations on archaeal pathways. In addition, we experimentally determined several parameters relevant to growth, including a characterization of the biomass composition and a quantification of carbon and oxygen consumption. Using the metabolic reconstruction and the experimental data, we formulated a constraints-based model which we used to analyze the behavior of the archaeon when grown on a single carbon source. Results of the analysis include the finding that Natronomonas pharaonis, when grown aerobically on acetate, uses a carbon to oxygen consumption ratio that is theoretically near-optimal with respect to growth and energy production. This supports the hypothesis that, under simple conditions, the microorganism optimizes its metabolism with respect to the two objectives. We also found that the archaeon has a very low carbon efficiency of only about 35%. This inefficiency is probably due to a very low P/O ratio as well as to the other difficulties posed by its extreme environment