Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla

<p>Abstract</p> <p>Background</p> <p>Omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in Gram-negative bacteria that infect vertebrates or plants. Despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacteria. To simulate the molecular adaptation of omptins, we applied site-specific mutagenesis to make Epo of the plant pathogenic <it>Erwinia pyrifoliae </it>exhibit virulence-associated functions of its close homolog, the plasminogen activator Pla of <it>Yersinia pestis</it>. We addressed three virulence-associated functions exhibited by Pla, i.e., proteolytic activation of plasminogen, proteolytic degradation of serine protease inhibitors, and invasion into human cells.</p> <p>Results</p> <p>Pla and Epo expressed in <it>Escherichia coli </it>are both functional endopeptidases and cleave human serine protease inhibitors, but Epo failed to activate plasminogen and to mediate invasion into a human endothelial-like cell line. Swapping of ten amino acid residues at two surface loops of Pla and Epo introduced plasminogen activation capacity in Epo and inactivated the function in Pla. We also compared the structure of Pla and the modeled structure of Epo to analyze the structural variations that could rationalize the different proteolytic activities. Epo-expressing bacteria managed to invade human cells only after all extramembranous residues that differ between Pla and Epo and the first transmembrane β-strand had been changed.</p> <p>Conclusions</p> <p>We describe molecular adaptation of a protease from an environmental setting towards a virulence factor detrimental for humans. Our results stress the evolvability of bacterial β-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens.</p

Evaluation of the fineness of degummed bast fibers

Fiber fineness characteristics are important for yarn production and quality. In this paper, degummed bast fibers such as hemp, flax and ramie have been examined with the Optical Fiber Diameter Analyzer (OFDA100 and OFDA2000) systems for fiber fineness, in comparison with the conventional image analysis and the Wira airflow tester. The correlation between the results from these measurements was analysed. The results indicate that there is a significant linear co-relation between the fiber fineness measurement results obtained from those different systems. In addition, the mean fiber width and its coefficient of variation obtained from the OFDA100 system are smaller than those obtained from the OFDA2000 system, due to the difference in sample preparation methods. The OFDA2000 system can also measure the fiber fineness profile along the bast fiber plants, which can be useful for plant breeding. <br /

Visual Working Memory Capacity and Proactive Interference

Background: Visual working memory capacity is extremely limited and appears to be relatively immune to practice effects or the use of explicit strategies. The recent discovery that visual working memory tasks, like verbal working memory tasks, are subject to proactive interference, coupled with the fact that typical visual working memory tasks are particularly conducive to proactive interference, suggests that visual working memory capacity may be systematically under-estimated. Methodology/Principal Findings: Working memory capacity was probed behaviorally in adult humans both in laboratory settings and via the Internet. Several experiments show that although the effect of proactive interference on visual working memory is significant and can last over several trials, it only changes the capacity estimate by about 15%. Conclusions/Significance: This study further confirms the sharp limitations on visual working memory capacity, both in absolute terms and relative to verbal working memory. It is suggested that future research take these limitations into account in understanding differences across a variety of tasks between human adults, prelinguistic infants and nonlinguistic animals

Sequential analysis of surfactant, lung function and inflammation in cystic fibrosis patients

BACKGROUND: In a cross-sectional analysis of cystic fibrosis (CF) patients with mild lung disease, reduced surfactant activity was correlated to increased neutrophilic airway inflammation, but not to lung function. So far, longitudinal measurements of surfactant function in CF patients are lacking and it remains unclear how these alterations relate to the progression of airway inflammation as well as decline in pulmonary function over time. METHODS: As part of the BEAT trial, a longitudinal study to assess the course of airway inflammation in CF, we studied lung function, surfactant function and endobronchial inflammation using bronchoalveolar lavage fluid from 20 CF patients with normal pulmonary function (median FEV(1 )94% of predicted) at three times over a three year period. RESULTS: There was a progressive loss of surfactant function, assessed as minimal surface tension. The decline in surfactant function was negatively correlated to an increase in neutrophilic inflammation and a decrease in lung function, assessed by FEV(1), MEF(75/25%VC), and MEF(25%VC). The concentrations of the surfactant specific proteins A, C and D did not change, whereas SP-B increased during this time period. CONCLUSION: Our findings suggest a link between loss of surfactant function driven by progressive airway inflammation and loss of small airway function in CF patients with limited lung disease

The neural correlates of dreaming.

Consciousness never fades during waking. However, when awakened from sleep, we sometimes recall dreams and sometimes recall no experiences. Traditionally, dreaming has been identified with rapid eye-movement (REM) sleep, characterized by wake-like, globally 'activated', high-frequency electroencephalographic activity. However, dreaming also occurs in non-REM (NREM) sleep, characterized by prominent low-frequency activity. This challenges our understanding of the neural correlates of conscious experiences in sleep. Using high-density electroencephalography, we contrasted the presence and absence of dreaming in NREM and REM sleep. In both NREM and REM sleep, reports of dream experience were associated with local decreases in low-frequency activity in posterior cortical regions. High-frequency activity in these regions correlated with specific dream contents. Monitoring this posterior 'hot zone' in real time predicted whether an individual reported dreaming or the absence of dream experiences during NREM sleep, suggesting that it may constitute a core correlate of conscious experiences in sleep

The Target Selective Neural Response — Similarity, Ambiguity, and Learning Effects

A network of frontal and parietal brain regions is commonly recruited during tasks that require the deliberate ‘top-down’ control of thought and action. Previously, using simple target detection, we have demonstrated that within this frontoparietal network, the right ventrolateral prefrontal cortex (VLPFC) in particular is sensitive to the presentation of target objects. Here, we use a range of target/non-target morphs to plot the target selective response within distinct frontoparietal sub-regions in greater detail. The increased resolution allows us to examine the extent to which different cognitive factors can predict the blood oxygenation level dependent (BOLD) response to targets. Our results reveal that both probability of positive identification (similarity to target) and proximity to the 50% decision boundary (ambiguity) are significant predictors of BOLD signal change, particularly in the right VLPFC. Furthermore, the profile of target related signal change is not static, with the degree of selectivity increasing as the task becomes familiar. These findings demonstrate that frontoparietal sub-regions are recruited under increased cognitive demand and that when recruited, they adapt, using both fast and slow mechanisms, to selectively respond to those items that are of the most relevance to current intentions

Structure and dynamics of the operon map of Buchnera aphidicola sp. strain APS

<p>Abstract</p> <p>Background</p> <p>Gene expression regulation is still poorly documented in bacteria with highly reduced genomes. Understanding the evolution and mechanisms underlying the regulation of gene transcription in <it>Buchnera aphidicola</it>, the primary endosymbiont of aphids, is expected both to enhance our understanding of this nutritionally based association and to provide an intriguing case-study of the evolution of gene expression regulation in a reduced bacterial genome.</p> <p>Results</p> <p>A Bayesian predictor was defined to infer the <it>B. aphidicola </it>transcription units, which were further validated using transcriptomic data and RT-PCR experiments. The characteristics of <it>B. aphidicola </it>predicted transcription units (TUs) were analyzed in order to evaluate the impact of operon map organization on the regulation of gene transcription.</p> <p>On average, <it>B. aphidicola </it>TUs contain more genes than those of <it>E. coli</it>. The global layout of <it>B. aphidicola </it>operon map was mainly shaped by the big reduction and the rearrangements events, which occurred at the early stage of the symbiosis. Our analysis suggests that this operon map may evolve further only by small reorganizations around the frontiers of <it>B. aphidicola </it>TUs, through promoter and/or terminator sequence modifications and/or by pseudogenization events. We also found that the need for specific transcription regulation exerts some pressure on gene conservation, but not on gene assembling in the operon map in <it>Buchnera</it>. Our analysis of the TUs spacing pointed out that a selection pressure is maintained on the length of the intergenic regions between divergent adjacent gene pairs.</p> <p>Conclusions</p> <p><it>B. aphidicola </it>can seemingly only evolve towards a more polycistronic operon map. This implies that gene transcription regulation is probably subject to weak selection pressure in <it>Buchnera </it>conserving operons composed of genes with unrelated functions.</p

Practice Induces Function-Specific Changes in Brain Activity

Practice can have a profound effect on performance and brain activity, especially if a task can be automated. Tasks that allow for automatization typically involve repeated encoding of information that is paired with a constant response. Much remains unknown about the effects of practice on encoding and response selection in an automated task.To investigate function-specific effects of automatization we employed a variant of a Sternberg task with optimized separation of activity associated with encoding and response selection by means of m-sequences. This optimized randomized event-related design allows for model free measurement of BOLD signals over the course of practice. Brain activity was measured at six consecutive runs of practice and compared to brain activity in a novel task.Prompt reductions were found in the entire cortical network involved in encoding after a single run of practice. Changes in the network associated with response selection were less robust and were present only after the third run of practice.This study shows that automatization causes heterogeneous decreases in brain activity across functional regions that do not strictly track performance improvement. This suggests that cognitive performance is supported by a dynamic allocation of multiple resources in a distributed network. Our findings may bear importance in understanding the role of automatization in complex cognitive performance, as increased encoding efficiency in early stages of practice possibly increases the capacity to otherwise interfering information

An Outer Membrane Receptor of Neisseria meningitidis Involved in Zinc Acquisition with Vaccine Potential

Since the concentration of free iron in the human host is low, efficient iron-acquisition mechanisms constitute important virulence factors for pathogenic bacteria. In Gram-negative bacteria, TonB-dependent outer membrane receptors are implicated in iron acquisition. It is far less clear how other metals that are also scarce in the human host are transported across the bacterial outer membrane. With the aim of identifying novel vaccine candidates, we characterized in this study a hitherto unknown receptor in Neisseria meningitidis. We demonstrate that this receptor, designated ZnuD, is produced under zinc limitation and that it is involved in the uptake of zinc. Upon immunization of mice, it was capable of inducing bactericidal antibodies and we could detect ZnuD-specific antibodies in human convalescent patient sera. ZnuD is highly conserved among N. meningitidis isolates and homologues of the protein are found in many other Gram-negative pathogens, particularly in those residing in the respiratory tract. We conclude that ZnuD constitutes a promising candidate for the development of a vaccine against meningococcal disease for which no effective universal vaccine is available. Furthermore, the results suggest that receptor-mediated zinc uptake represents a novel virulence mechanism that is particularly important for bacterial survival in the respiratory tract

Representing Where along with What Information in a Model of a Cortical Patch

Behaving in the real world requires flexibly combining and maintaining information about both continuous and discrete variables. In the visual domain, several lines of evidence show that neurons in some cortical networks can simultaneously represent information about the position and identity of objects, and maintain this combined representation when the object is no longer present. The underlying network mechanism for this combined representation is, however, unknown. In this paper, we approach this issue through a theoretical analysis of recurrent networks. We present a model of a cortical network that can retrieve information about the identity of objects from incomplete transient cues, while simultaneously representing their spatial position. Our results show that two factors are important in making this possible: A) a metric organisation of the recurrent connections, and B) a spatially localised change in the linear gain of neurons. Metric connectivity enables a localised retrieval of information about object identity, while gain modulation ensures localisation in the correct position. Importantly, we find that the amount of information that the network can retrieve and retain about identity is strongly affected by the amount of information it maintains about position. This balance can be controlled by global signals that change the neuronal gain. These results show that anatomical and physiological properties, which have long been known to characterise cortical networks, naturally endow them with the ability to maintain a conjunctive representation of the identity and location of objects