The Yersinia YopE and YopH type III effector proteins enhance bacterial proliferation following contact with eukaryotic cells

BACKGROUND: Several bacterial pathogens express antihost factors that likely decrease both their maximal growth rate (due to metabolic costs) as well as their mortality rate (by neutralizing host defenses). The pathogenic yersiniae make a huge metabolic investment expressing virulence proteins (referred to as Yops) that are directly injected into eukaryotic cells and that modulate host defense responses such as phagocytosis and stress-activated signaling pathways. Although host-cell contact enhanced Yop expression as well as the cellular activities of several Yops have recently been described, a clear link between these phenomena and bacterial survival and/or proliferation remains to be established RESULTS: We show that the proliferation of Y. pseudotuberculosis is compromised when the bacterium is growing in association with eukaryotic cells compared to free-living bacteria. One factor likely limiting Yersinia proliferation is the metabolically taxing expression of yopE which we show using flow cytometry increases in individual bacteria following their contact with cultured macrophage-like cells. An additional factor limiting Y. pseudotuberculosis proliferation are host cell defense systems which can be significantly ameliorated by disrupting the host cell cytoskeletal system by either exogenously added toxins or by the bacterial-mediated injection of YopE or YopH. CONCLUSIONS: Our results demonstrate that despite their metabolic costs the Yop virulence proteins play an important role in enabling Y. pseudotuberculosis to survive and proliferate when confronted with the antimicrobial activities of the eukaryotic cell

Type IV Pili in Francisella – A Virulence Trait in an Intracellular Pathogen

Francisella tularensis is a highly virulent intracellular human pathogen that is capable of rapid proliferation in the infected host. Mutants affected in intracellular survival and growth are highly attenuated which highlights the importance of the intracellular phase of the infection. Genomic analysis has revealed that Francisella encodes all genes required for expression of functional type IV pili (Tfp), and in this focused review we summarize recent findings regarding this system in the pathogenesis of tularemia. Tfp are dynamic adhesive structures that have been identified as major virulence determinants in several human pathogens, but it is not obvious what role these structures could have in an intracellular pathogen like Francisella. In the human pathogenic strains, genes required for secretion and assembly of Tfp and one pilin, PilA, have shown to be required for full virulence. Importantly, specific genetic differences have been identified between the different Francisella subspecies where in the most pathogenic type A variants all genes are intact while several Tfp genes are pseudogenes in the less pathogenic type B strains. This suggests that there has been a selection for expression of Tfp with different properties in the different subspecies. There is also a possibility that the genetic differences reflect adaptation to different environmental niches of the subspecies and plays a role in transmission of tularemia. This is also in line with recent findings where Tfp pilins are found to be glycosylated which could reflect a role for Tfp in the environment to promote survival and transmission. We are still far from understanding the role of Tfp in virulence and transmission of tularemia, but with the genomic information and genetic tools available we are in a good position to address these issues in the future

Vibronic structure in triatomic molecules : The hydrocarbon flame bands of the formyl radical (HCO). A theoretical study

A theoretical study of the vibrational structure of the math 2A′ ground and math 2A′ excited states of the formyl radical, HCO, and its deuterated form, DCO, has been performed. The potential energy surfaces have been computed by means of a multiconfigurational perturbative method, CASPT2. The computed geometries and the harmonic and anharmonic frequencies are successfully compared to the available experimental information. The vibrational intensities of the transition math 2A′↔math 2A′ have been computed both for absorption and emission. The results lead to accurate determinations of several structural parameters and some reassignments of the vibrational transitions of the so-called hydrocarbon flame bands of the formyl [email protected]

The Feasibility and Potential of Training Correctional Officers in Flexible Styles of Communication to Reduce Burnout: A Multiple Baseline Trial in Real-Life Settings

Background: Burnout is typically high among correctional officers. By a training intervention in the flexible communication style ‘everyday conversations’ as a way to increase job-related resources, this study aimed to reduce burnout in Swedish correctional officers. Methods: In a stepped wedged waiting list design, 13 prison wards with 266 employees were randomized to the everyday conversations intervention at different time points during the study period. Burnout was measured using the Maslach Burnout Inventory-General Survey scales over 16 time points. Results: A significant reduction in cynicism was found. In addition, moderation effects relating to personal motivators and characteristics were found. Conclusion: There is feasibility and potential to implement communication skills to reduce burnout among employees in real-life prison settings

A theoretical study of the 1B2u and 1B1u vibronic bands in benzene

The two lowest bands, 1B2u and 1B1u, of the electronic spectrum of the benzene molecule have been studied theoretically using a new method to compute vibronic excitation energies and intensities. The complete active space (CAS) self-contained field (SCF) method (with six active π-orbitals) was used to compute harmonic force field for the ground state and the 1B2u and 1B1u electronic states. A linear approximation has been used for the transition dipole as a function of the nuclear displacement coordinates. Derivatives of the transition dipole were computed using a variant of the CASSCF state interaction method. Multiconfigurational second-order perturbation theory (CASPT2) was used to obtain absolute excitation energies (12 active π-orbitals). The results show that the approach works well. Vibrational progressions are well described in both bands and intensities, and energies are in agreement with experiment, in particular when CASPT2 derived geometries are used. One interesting result is that computed vertical energies fall about 0.1 eV on the high energy side of the band [email protected]

The type IV pilin, PilA, is required for full virulence of Francisella tularensis subspecies tularensis

Published onlineJournal ArticleThis is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: All four Francisella tularensis subspecies possess gene clusters with potential to express type IV pili (Tfp). These clusters include putative pilin genes, as well as pilB, pilC and pilQ, required for secretion and assembly of Tfp. A hallmark of Tfp is the ability to retract the pilus upon surface contact, a property mediated by the ATPase PilT. Interestingly, out of the two major human pathogenic subspecies only the highly virulent type A strains have a functional pilT gene. RESULTS: In a previous study, we were able to show that one pilin gene, pilA, was essential for virulence of a type B strain in a mouse infection model. In this work we have examined the role of several Tfp genes in the virulence of the pathogenic type A strain SCHU S4. pilA, pilC, pilQ, and pilT were mutated by in-frame deletion mutagenesis. Interestingly, when mice were infected with a mixture of each mutant strain and the wild-type strain, the pilA, pilC and pilQ mutants were out-competed, while the pilT mutant was equally competitive as the wild-type. CONCLUSIONS: This suggests that expression and surface localisation of PilA contribute to virulence in the highly virulent type A strain, while PilT was dispensable for virulence in the mouse infection model

Nassau Senior : Period considered 1829 - 1836

This paper concerns the ideas on society, policies and economic thoughts on Ireland before the cataclysmal famine of the 1840s. Senior, classified as one of the classical economists, elaborated these in the period 1829 – 1836, thus during the period of Parliamentary reform. As a trusted counsellor of the Whig governments, Senior advocated measures opposite to the common notions of laissez-faire. His basic ideas are contrasted to those of Malthus concerning economics and, in particular, the population doctrine that Senior never believed in and in its crudest form refuted. Senior regarded Malthus’ doctrine as devastating to governmental policies. Senior wanted an efficient and strong government. Moreover, Senior evolved ideas, in fact a strategy, for raising Ireland out of her common destitution instead of institutionalizing poor laws. This strategy embraced Catholic emancipation, education, public investments in infrastructure and emigration. His ideas, and proposals akin to Senior’s, are related to the political discourse of the day, which took a more common view of laissez-faire during the period considered. Nevertheless, there is consistency in his ideas on government, public investments and laissez-faire. Senior cannot be described as anything other than an early liberal and a classical economist and, hence, an advocator of economic laissez-faire. This paper underlines the need for a clear distinction between economic laissez-faire as a concept and the concept of political laissez-faire, whereas the former concerns thoughts on economics and the latter is related to the notion of the impassivity of the period of today’s discourse

Nassau Senior : Period considered 1829 - 1836

This paper concerns the ideas on society, policies and economic thoughts on Ireland before the cataclysmal famine of the 1840s. Senior, classified as one of the classical economists, elaborated these in the period 1829 – 1836, thus during the period of Parliamentary reform. As a trusted counsellor of the Whig governments, Senior advocated measures opposite to the common notions of laissez-faire. His basic ideas are contrasted to those of Malthus concerning economics and, in particular, the population doctrine that Senior never believed in and in its crudest form refuted. Senior regarded Malthus’ doctrine as devastating to governmental policies. Senior wanted an efficient and strong government. Moreover, Senior evolved ideas, in fact a strategy, for raising Ireland out of her common destitution instead of institutionalizing poor laws. This strategy embraced Catholic emancipation, education, public investments in infrastructure and emigration. His ideas, and proposals akin to Senior’s, are related to the political discourse of the day, which took a more common view of laissez-faire during the period considered. Nevertheless, there is consistency in his ideas on government, public investments and laissez-faire. Senior cannot be described as anything other than an early liberal and a classical economist and, hence, an advocator of economic laissez-faire. This paper underlines the need for a clear distinction between economic laissez-faire as a concept and the concept of political laissez-faire, whereas the former concerns thoughts on economics and the latter is related to the notion of the impassivity of the period of today’s discourse