Facile Production of the Pseudomonas aeruginosa Virulence Factor LasB in Escherichia coli for Structure-Based Drug Design

The human pathogen Pseudomonas aeruginosa has a number of virulence factors at its disposal that play crucial roles in the progression of infection. LasB is one of the major virulence factors and exerts its effects through elastolytic and proteolytic activities aimed at dissolving connective tissue and inactivating host defense proteins. LasB is of great interest for the development of novel pathoblockers to temper the virulence, but access has thus far largely been limited to protein isolated from Pseudomonas cultures. Here, we describe a new protocol for high-level production of native LasB in Escherichia coli. We demonstrate that this facile approach is suitable for the production of mutant, thus far inaccessible LasB variants, and characterize the proteins biochemically and structurally. We expect that easy access to LasB will accelerate the development of inhibitors for this important virulence factor

Scalable target detection for large robot teams

In this paper, we present an asynchronous display method, coined image queue, which allows operators to search through a large amount of data gathered by autonomous robot teams. We discuss and investigate the advantages of an asynchronous display for foraging tasks with emphasis on Urban Search and Rescue. The image queue approach mines video data to present the operator with a relevant and comprehensive view of the environment in order to identify targets of interest such as injured victims. It fills the gap for comprehensive and scalable displays to obtain a network-centric perspective for UGVs. We compared the image queue to a traditional synchronous display with live video feeds and found that the image queue reduces errors and operator's workload. Furthermore, it disentangles target detection from concurrent system operations and enables a call center approach to target detection. With such an approach we can scale up to very large multi-robot systems gathering huge amounts of data that is then distributed to multiple operators. Copyright 2011 ACM

A novel mouse model of Campylobacter jejuni enteropathy and diarrhea

Campylobacter infections are among the leading bacterial causes of diarrhea and of ‘environmental enteropathy’ (EE) and growth failure worldwide. However, the lack of an inexpensive small animal model of enteric disease with Campylobacter has been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe a robust standard mouse model that can exhibit reproducible bloody diarrhea or growth failure, depending on the zinc or protein deficient diet and on antibiotic alteration of normal microbiota prior to infection. Zinc deficiency and the use of antibiotics create a niche for Campylobacter infection to establish by narrowing the metabolic flexibility of these mice for pathogen clearance and by promoting intestinal and systemic inflammation. Several biomarkers and intestinal pathology in this model also mimic those seen in human disease. This model provides a novel tool to test specific hypotheses regarding disease pathogenesis as well as vaccine development that is currently in progress

Human Interaction with Robot Swarms: A Survey

Recent advances in technology are delivering robots of reduced size and cost. A natural outgrowth of these advances are systems comprised of large numbers of robots that collaborate autonomously in diverse applications. Research on effective autonomous control of such systems, commonly called swarms, has increased dramatically in recent years and received attention from many domains, such as bioinspired robotics and control theory. These kinds of distributed systems present novel challenges for the effective integration of human supervisors, operators, and teammates that are only beginning to be addressed. This paper is the first survey of human–swarm interaction (HSI) and identifies the core concepts needed to design a human–swarm system. We first present the basics of swarm robotics. Then, we introduce HSI from the perspective of a human operator by discussing the cognitive complexity of solving tasks with swarm systems. Next, we introduce the interface between swarm and operator and identify challenges and solutions relating to human–swarm communication, state estimation and visualization, and human control of swarms. For the latter, we develop a taxonomy of control methods that enable operators to control swarms effectively. Finally, we synthesize the results to highlight remaining challenges, unanswered questions, and open problems for HSI, as well as how to address them in future works

Diagnose und Therapie okulomotorischer Defizite bei Patienten mit Möbius-Sequenz

Der Artikel gibt einen Überblick über das Spektrum möglicher Motilitätseinschränkungen und Stellungsanomalien der Augen bei Patienten mit Möbius-Sequenz. Die augenmuskelchirurgischen Behandlungsoptionen werden diskutiert und es wird ein operatives Stufenschema vorgestellt

Diabetes is a Risk Factor for Pulmonary Tuberculosis: A Case-Control Study from Mwanza, Tanzania.

Diabetes and TB are associated, and diabetes is increasingly common in low-income countries where tuberculosis (TB) is highly endemic. However, the role of diabetes for TB has not been assessed in populations where HIV is prevalent. A case-control study was conducted in an urban population in Tanzania among culture-confirmed pulmonary TB patients and non-TB neighbourhood controls. Participants were tested for diabetes according to WHO guidelines and serum concentrations of acute phase reactants were measured. The association between diabetes and TB, and the role of HIV as an effect modifier, were examined using logistic regression. Since blood glucose levels increase during the acute phase response, we adjusted for elevated serum acute phase reactants. Among 803 cases and 350 controls the mean (SD) age was 34.8 (11.9) and 33.8 (12.0) years, and the prevalence of diabetes was 16.7% (95% CI: 14.2; 19.4) and 9.4% (6.6; 13.0), respectively. Diabetes was associated with TB (OR 2.2, 95% CI: 1.5; 3.4, p<0.001). However, the association depended on HIV status (interaction, p = 0.01) due to a stronger association among HIV uninfected (OR 4.2, 95% CI: 1.5; 11.6, p = 0.01) compared to HIV infected (OR 0.1, 95% CI: 0.01; 1.8, p = 0.13) after adjusting for age, sex, demographic factors and elevated serum acute phase reactants. Diabetes is a risk factor for TB in HIV uninfected, whereas the association in HIV infected patients needs further study. The increasing diabetes prevalence may be a threat to TB control

Nucleon Spin-Polarisabilities from Polarisation Observables in Low-Energy Deuteron Compton Scattering

We investigate the dependence of polarisation observables in elastic deuteron Compton scattering below the pion production threshold on the spin-independent and spin-dependent iso-scalar dipole polarisabilities of the nucleon. The calculation uses Chiral Effective Field Theory with dynamical Delta(1232) degrees of freedom in the Small Scale Expansion at next-to-leading order. Resummation of the NN intermediate rescattering states and including the Delta induces sizeable effects. The analysis considers cross-sections and the analysing power of linearly polarised photons on an unpolarised target, and cross-section differences and asymmetries of linearly and circularly polarised beams on a vector-polarised deuteron. An intuitive argument helps one to identify kinematics in which one or several polarisabilities do not contribute. Some double-polarised observables are only sensitive to linear combinations of two of the spin-polarisabilities, simplifying a multipole-analysis of the data. Spin-polarisabilities can be extracted at photon energies \gtrsim 100 MeV, after measurements at lower energies of \lesssim 70 MeV provide high-accuracy determinations of the spin-independent ones. An interactive Mathematica 7.0 notebook of our findings is available from [email protected]: 30 pages LaTeX2e, including 22 figures as 66 .eps file embedded with includegraphicx; three errors in initial submission corrected. This submission includes ot the erratum to be published in EPJA (2012) and the corrections in the tex

Polarity of uncertainty representation during exploration and exploitation in ventromedial prefrontal cortex

Environments furnish multiple information sources for making predictions about future events. Here we use behavioural modelling and functional magnetic resonance imaging to describe how humans select predictors that might be most relevant. First, during early encounters with potential predictors, participants’ selections were explorative and directed towards subjectively uncertain predictors (positive uncertainty effect). This was particularly the case when many future opportunities remained to exploit knowledge gained. Then, preferences for accurate predictors increased over time, while uncertain predictors were avoided (negative uncertainty effect). The behavioural transition from positive to negative uncertainty-driven selections was accompanied by changes in the representations of belief uncertainty in ventromedial prefrontal cortex (vmPFC). The polarity of uncertainty representations (positive or negative encoding of uncertainty) changed between exploration and exploitation periods. Moreover, the two periods were separated by a third transitional period in which beliefs about predictors’ accuracy predominated. The vmPFC signals a multiplicity of decision variables, the strength and polarity of which vary with behavioural context

A pivotal role for starch in the reconfiguration of 14C-partitioning and allocation in Arabidopsis thaliana under short-term abiotic stress.

Plant carbon status is optimized for normal growth but is affected by abiotic stress. Here, we used 14C-labeling to provide the first holistic picture of carbon use changes during short-term osmotic, salinity, and cold stress in Arabidopsis thaliana. This could inform on the early mechanisms plants use to survive adverse environment, which is important for efficient agricultural production. We found that carbon allocation from source to sinks, and partitioning into major metabolite pools in the source leaf, sink leaves and roots showed both conserved and divergent responses to the stresses examined. Carbohydrates changed under all abiotic stresses applied; plants re-partitioned 14C to maintain sugar levels under stress, primarily by reducing 14C into the storage compounds in the source leaf, and decreasing 14C into the pools used for growth processes in the roots. Salinity and cold increased 14C-flux into protein, but as the stress progressed, protein degradation increased to produce amino acids, presumably for osmoprotection. Our work also emphasized that stress regulated the carbon channeled into starch, and its metabolic turnover. These stress-induced changes in starch metabolism and sugar export in the source were partly accompanied by transcriptional alteration in the T6P/SnRK1 regulatory pathway that are normally activated by carbon starvation

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children