Summary
Porcine pleuropneumonia, caused by the bacterial porcine respiratory tract pathogen Actinobacillus pleuropneumoniae, leads to high economic losses in affected swine herds in most countries of ...the world. Pigs affected by peracute and acute disease suffer from severe respiratory distress with high lethality. The agent was first described in 1957 and, since then, knowledge about the pathogen itself, and its interactions with the host, has increased continuously. This is, in part, due to the fact that experimental infections can be studied in the natural host. However, the fact that most commercial pigs are colonized by this pathogen has hampered the applicability of knowledge gained under experimental conditions. In addition, several factors are involved in development of disease, and these have often been studied individually. In a DISCONTOOLS initiative, members from science, industry and clinics exchanged their expertise and empirical observations and identified the major gaps in knowledge. This review sums up published results and expert opinions, within the fields of pathogenesis, epidemiology, transmission, immune response to infection, as well as the main means of prevention, detection and control. The gaps that still remain to be filled are highlighted, and present as well as future challenges in the control of this disease are addressed.
The technological appeal of multiferroics is the ability to control magnetism with electric field. For devices to be useful, such control must be achieved at room temperature. The only single-phase ...multiferroic material exhibiting unambiguous magnetoelectric coupling at room temperature is BiFeO3 (refs 4 and 5). Its weak ferromagnetism arises from the canting of the antiferromagnetically aligned spins by the Dzyaloshinskii-Moriya (DM) interaction. Prior theory considered the symmetry of the thermodynamic ground state and concluded that direct 180-degree switching of the DM vector by the ferroelectric polarization was forbidden. Instead, we examined the kinetics of the switching process, something not considered previously in theoretical work. Here we show a deterministic reversal of the DM vector and canted moment using an electric field at room temperature. First-principles calculations reveal that the switching kinetics favours a two-step switching process. In each step the DM vector and polarization are coupled and 180-degree deterministic switching of magnetization hence becomes possible, in agreement with experimental observation. We exploit this switching to demonstrate energy-efficient control of a spin-valve device at room temperature. The energy per unit area required is approximately an order of magnitude less than that needed for spin-transfer torque switching. Given that the DM interaction is fundamental to single-phase multiferroics and magnetoelectrics, our results suggest ways to engineer magnetoelectric switching and tailor technologically pertinent functionality for nanometre-scale, low-energy-consumption, non-volatile magnetoelectronics.
•This ESMO Clinical Practice Guideline provides key recommendations for managing endometrial cancer.•The guideline covers clinical and pathological diagnosis, staging and risk assessment, treatment ...and follow-up.•Treatment and management algorithms according to risk groups and for advanced/metastatic or recurrent disease are provided.•Authorship includes a multidisciplinary group of experts from different institutions in Europe, the USA and South America.•Recommendations are based on available scientific data and the authors’ collective expert opinion.
Actinobacillus pleuropneumoniae is a Gram-negative bacterium belonging to the Pasteurellaceae family and the causative agent of porcine pleuropneumonia, a highly contagious lung disease causing ...important economic losses. Surface polysaccharides, including lipopolysaccharides (LPS) and capsular polysaccharides (CPS), are implicated in the adhesion and virulence of A. pleuropneumoniae, but their role in biofilm formation is still unclear. In this study, we investigated the requirement for these surface polysaccharides in biofilm formation by A. pleuropneumoniae serotype 1. Well-characterized mutants were used: an O-antigen LPS mutant, a truncated core LPS mutant with an intact O antigen, a capsule mutant, and a poly-N-acetylglucosamine (PGA) mutant. We compared the amount of biofilm produced by the parental strain and the isogenic mutants using static and dynamic systems. Compared to the findings for the biofilm of the parental or other strains, the biofilm of the O antigen and the PGA mutants was dramatically reduced, and it had less cell-associated PGA. Real-time PCR analyses revealed a significant reduction in the level of pgaA, cpxR, and cpxA mRNA in the biofilm cells of the O-antigen mutant compared to that in the biofilm cells of the parental strain. Specific binding between PGA and LPS was consistently detected by surface plasmon resonance, but the lack of O antigen did not abolish these interactions. In conclusion, the absence of the O antigen reduces the ability of A. pleuropneumoniae to form a biofilm, and this is associated with the reduced expression and production of PGA.
We describe a highly sensitive and specific multiplex PCR, based on capsular loci and the species specific apxIV gene, that unequivocally differentiates serovar 3, 6, and 8 Actinobacillus ...pleuropneumoniae strains that are cross-reactive in conventional immunological tests.
Background
Asthma is an inflammatory disease that involves airway hyper‐responsiveness and mucus hypersecretion. The LIM‐only protein FHL2 is a crucial modulator of multiple signal transduction ...pathways and functions as a scaffold in specific protein–protein interactions.
Objective
We sought to investigate the role of FHL2 in airway inflammation.
Methods
Allergic airway inflammation was induced in WT and FHL2‐knock out (FHL2‐KO) mice with ovalbumin (OVA). Lung tissue, bronchoalveolar lavage fluid (BALF) and draining lymph node cells were analysed for inflammation. FHL2 loss and gain of function studies were performed in lung epithelial cells.
Results
FHL2‐deficient mice challenged with OVA show significantly reduced airway inflammation as evidenced by reduced infiltration of inflammatory cells including eosinophils, dendritic cells, B cells and T cells. Furthermore, mucus production was decreased in FHL2‐KO mice. In BALF, the levels of IL‐5, IL‐13, eotaxin‐1 and eotaxin‐2 were significantly lower in FHL2‐KO mice. In addition, draining lymph node cells from FHL2‐KO mice show reduced levels of IL‐5 and IL‐13. Consistent with this, OVA‐specific serum IgG and IgE levels were reduced in FHL2‐KO mice. We also found that phosphorylation of ERK1/2 is markedly attenuated in FHL2‐KO lung. Knock‐down of FHL2 in human lung epithelial cells resulted in a striking decrease in ERK1/2 phosphorylation and mRNA levels of inflammatory cytokines and MUC5AC, whereas FHL2 overexpression exhibited opposite effects. Finally, the SNP rs4851765 shows an association with the severity of bronchial hyper‐responsiveness.
Conclusion
These results highlight functional involvement of FHL2 in airway inflammation and identify FHL2 as a novel gene associated with asthma severity in human.
Actinobacillus pleuropneumoniae causes porcine pleuropneumonia, a highly contagious disease for which there is no effective vaccine. This review considers how adhesins, iron-acquisition factors, ...capsule and lipopolysaccharide, RTX cytotoxins and other potential future vaccine components contribute to colonisation, to avoidance of host clearance mechanisms and to damage of host tissues.