The amoebal MAP kinase response to Legionella pneumophila is regulated by DupA

SummaryThe amoeba Dictyostelium discoideum can support replication of Legionella pneumophila. Here we identify the dupA gene, encoding a putative tyrosine kinase/dual-specificity phosphatase, in a screen for D. discoideum mutants altered in allowing L. pneumophila intracellular replication. Inactivation of dupA resulted in depressed L. pneumophila growth and sustained hyperphosphorylation of the amoebal MAP kinase ERK1, consistent with loss of a phosphatase activity. Bacterial challenge of wild-type amoebae induced dupA expression and resulted in transiently increased ERK1 phosphorylation, suggesting that dupA and ERK1 are part of a response to bacteria. Indeed, over 500 of the genes misregulated in the dupA− mutant were regulated in response to L. pneumophila infection, including some thought to have immune-like functions. MAP kinase phosphatases are known to be highly upregulated in macrophages challenged with L. pneumophila. Thus, DupA may regulate a MAP kinase response to bacteria that is conserved from amoebae to mammals

Analysis of the capability of cork and cork agglomerates to absorb multiple compressive quasi-static loading cycles

Despite the higher specific mechanical properties and the lower density of polymeric foams, these materials present cumulative damage behaviour that implies in the second and successive impacts, their mechanical properties decrease drastically. However, cork and cork agglomerates have the ability to absorb multiple impacts so they could be a more suitable material in some products, such as bumpers and helmets. This article is focused on the study of five different cork agglomerates and a natural cork under four different maximum deformations subjected to four consecutive compression loading cycles. Main diagrams, such as the stress–strain, energy density and efficiency, and the variation in diverse parameters, such as the absorbed energy density and maximum efficiency, were investigated and compared with an expanded polystyrene foam

Characterization of cork and cork agglomerates under compressive loads by means of energy absorption diagrams

Cork and cork agglomerates could be suitable replacements for petroleum-based polymeric foams due to their similar internal structure of cells and grains. Additionally, cork products have a renewable origin and are recyclable. Despite these notable properties, few studies have analysed the mechanical properties, especially the specific properties, of these materials under compressive loads. Moreover, although efficiency, ideality, and energy-normalized stress diagrams are commonly used for polymeric foams and 3D-printed lattice structures, these types of diagrams are not yet applied to cork products. It must be highlighted that efficiency diagrams are plotted only against nonspecific properties so, this article proposes additionally the use of nonspecific properties to compare materials not only in terms of properties per unit volume instead but also in terms of properties per unit mass that is more suitable for certain applications in which the weight is crucial. The materials studied herein include three different white cork agglomerates, a brown cork agglomerate, a black cork agglomerate, natural cork, and expanded polystyrene foam, which are subjected to quasi-static compressive loads

Widespread duplications in the genomes of laboratory stocks of Dictyostelium discoideum.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Duplications of stretches of the genome are an important source of individual genetic variation, but their unrecognized presence in laboratory organisms would be a confounding variable for genetic analysis. RESULTS: We report here that duplications of 15 kb or more are common in the genome of the social amoeba Dictyostelium discoideum. Most stocks of the axenic 'workhorse' strains Ax2 and Ax3/4 obtained from different laboratories can be expected to carry different duplications. The auxotrophic strains DH1 and JH10 also bear previously unreported duplications. Strain Ax3/4 is known to carry a large duplication on chromosome 2 and this structure shows evidence of continuing instability; we find a further variable duplication on chromosome 5. These duplications are lacking in Ax2, which has instead a small duplication on chromosome 1. Stocks of the type isolate NC4 are similarly variable, though we have identified some approximating the assumed ancestral genotype. More recent wild-type isolates are almost without large duplications, but we can identify small deletions or regions of high divergence, possibly reflecting responses to local selective pressures. Duplications are scattered through most of the genome, and can be stable enough to reconstruct genealogies spanning decades of the history of the NC4 lineage. The expression level of many duplicated genes is increased with dosage, but for others it appears that some form of dosage compensation occurs. CONCLUSION: The genetic variation described here must underlie some of the phenotypic variation observed between strains from different laboratories. We suggest courses of action to alleviate the problem.Published versio

Elucidating the Complex Interactions between Stress and Epileptogenic Pathways

Clinical and experimental data suggest that stress contributes to the pathology of epilepsy. We review mechanisms by which stress, primarily via stress hormones, may exacerbate epilepsy, focusing on the intersection between stress-induced pathways and the progression of pathological events that occur before, during, and after the onset of epileptogenesis. In addition to this temporal nuance, we discuss other complexities in stress-epilepsy interactions, including the role of blood-brain barrier dysfunction, neuron-glia interactions, and inflammatory/cytokine pathways that may be protective or damaging depending on context. We advocate the use of global analytical tools, such as microarray, in support of a shift away from a narrow focus on seizures and towards profiling the complex, early process of epileptogenesis, in which multiple pathways may interact to dictate the ultimate onset of chronic, recurring seizures

Genome-wide RNAi selection identifies a regulator of transmission stage-enriched gene families and cell-type differentiation in <i>Trypanosoma brucei</i>

<div><p><i>Trypanosoma brucei</i>, causing African sleeping-sickness, exploits quorum-sensing (QS) to generate the ‘stumpy forms’ necessary for the parasite’s transmission to tsetse-flies. These quiescent cells are generated by differentiation in the bloodstream from proliferative slender forms. Using genome-wide RNAi selection we screened for repressors of transmission stage-enriched mRNAs in slender forms, using the stumpy-elevated ESAG9 transcript as a model. This identified <i>REG9</i>.<i>1</i>, whose RNAi-silencing alleviated <i>ESAG9</i> repression in slender forms and tsetse-midgut procyclic forms. Interestingly, trypanosome surface protein Family 5 and Family 7 mRNAs were also elevated, which, like <i>ESAG9</i>, are <i>T</i>. <i>brucei</i> specific and stumpy-enriched. We suggest these contribute to the distinct transmission biology and vector tropism of <i>T</i>. <i>brucei</i> from other African trypanosome species. As well as surface family regulation, <i>REG9</i>.<i>1</i>-depletion generated QS-independent development to stumpy forms <i>in vivo</i>, whereas <i>REG9</i>.<i>1</i> overexpression in bloodstream forms potentiated spontaneous differentiation to procyclic forms in the absence of an external signal. Combined, this identifies <i>REG9</i>.<i>1</i> as a regulator of developmental cell fate, controlling the expression of <i>Trypanosoma brucei</i>-specific molecules elevated during transmission.</p></div

Observation of Amounts of Movement Practice Provided during Stroke Rehabilitation

Objective To investigate how much movement practice occurred during stroke rehabilitation, and what factors might influence doses of practice provided. Design Observational survey of stroke therapy sessions. Setting Seven inpatient and outpatient rehabilitation sites. Participants We observed a convenience sample of 312 physical and occupational therapy sessions for people with stroke. Interventions Not applicable. Main Outcome Measures We recorded numbers of repetitions in specific movement categories and data on potential modifying factors (patient age, side affected, time since stroke, FIM item scores, years of therapist experience). Descriptive statistics were used to characterize amounts of practice. Correlation and regression analyses were used to determine whether potential factors were related to the amount of practice in the 2 important categories of upper extremity functional movements and gait steps. Results Practice of task-specific, functional upper extremity movements occurred in 51% of the sessions that addressed upper limb rehabilitation, and the average number of repetitions/session was 32 (95% confidence interval [CI]=20–44). Practice of gait occurred in 84% of sessions that addressed lower limb rehabilitation and the average number of gait steps/session was 357 (95% CI=296–418). None of the potential factors listed accounted for significant variance in the amount of practice in either of these 2 categories. Conclusions The amount of practice provided during poststroke rehabilitation is small compared with animal models. It is possible that current doses of task-specific practice during rehabilitation are not adequate to drive the neural reorganization needed to promote function poststroke optimally

A gene expression comparison of Trypanosoma brucei and Trypanosoma congolense in the bloodstream of the mammalian host reveals species-specific adaptations to density-dependent development

In the bloodstream of mammalian hosts Trypanosoma brucei undergoes well-characterised density-dependent growth control and developmental adaptation for transmission. This involves the differentiation from proliferative, morphologically 'slender' forms to quiescent 'stumpy' forms that preferentially infect the tsetse fly vector. Another important livestock trypanosome, Trypanosoma congolense, also undergoes density-dependent cell-cycle arrest although this is not linked to obvious morphological transformation. Here we have compared the gene expression profile of T. brucei and T. congolense during the ascending phase of the parasitaemia and at peak parasitaemia in mice, analysing species and developmental differences between proliferating and cell-cycle arrested forms. Despite underlying conservation of their quorum sensing signalling pathway, each species exhibits distinct profiles of gene regulation when analysed by orthogroup and cell surface phylome profiling. This analysis of peak parasitaemia T. congolense provides the first molecular signatures of potential developmental competence, assisting life cycle developmental studies in these important livestock parasites. Furthermore, comparison with T. brucei identifies candidate molecules from each species that may be important for their survival in the mammalian host, transmission or distinct tropism in the tsetse vector