Mycoplasma hyopneumoniae evades phagocytic uptake by porcine alveolar macrophages in vitro

Mycoplasma hyopneumoniae, the agent of porcine enzootic pneumonia (EP), is able to persist in the lung tissue and evade destruction by the host for several weeks. To understand the mechanism of pathogen survival, phagocytic uptake of M. hyopneumoniae by primary porcine alveolar macrophages was investigated. Intracellular location and survival of the pathogen were explored using gentamicin survival assays, flow cytometry and confocal microscopy of M. hyopneumoniae 232 labelled with green fluorescent protein (GFP). Following 1 h and 16 h of co-incubation, few viable M. hyopneumoniae were recovered from inside macrophages. Flow cytometric analysis of macrophages incubated with M. hyopneumoniae expressing GFP indicated that the mycoplasmas became associated with macrophages, but were shown to be extracellular when actin-dependent phagocytosis was blocked with cytochalasin D. Confocal microscopy detected GFP-labelled M. hyopneumoniae inside macrophages and the numbers increased modestly with time of incubation. Neither the addition of porcine serum complement or convalescent serum from EP-recovered pigs was able to enhance engulfment of M. hyopneumoniae. This investigation suggests that M. hyopneumoniae evades significant uptake by porcine alveolar macrophages and this may be a mechanism of immune escape by M. hyopneumoniae in the porcine respiratory tract

English borrowings in the Spanish language: language policy of the Royal Academy of the Spanish language and the Fundéu BBVA regarding anglicisms

We can observe a rather purist attitude of certain Spanish institutions towards the use of anglicisms in the Spanish language.This difference in attitudes towards openness to other languages between the various countries may be explained by, among other things, the existence of linguistic institutions such as the Royal Academy of the Spanish Language (La Real Academia Española) and the Foundation of Urgent Spanish (Fundéu BBVA), which, according to many researchers, follow a restrictive policy against the use of anglicism

To the development of intelligent adaptive learning systems

The article describes the prospects for creating an informational adaptive automated learning system (based on the English Language) using advanced artificial intelligence technologies. In particular, the work shows that the quality of education largely depends on the form of educational content and the parameters of the learning object (a student) associated with its perception of informatio

Budesonide Enhances Agonist-Induced Bronchodilation in Human Small Airways by Increasing cAMP Production in Airway Smooth Muscle

The non-genomic mechanisms by which glucocorticoids modulate β2 agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E2 (PGE2), cholera toxin (CTX) or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE2, or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation of myosin light chain, a necessary signaling event mediating force generation. In parallel studies, cAMP levels were augmented by simultaneous exposure of HASM cells to formoterol and budesonide. Budesonide, fluticasone and prednisone alone rapidly increased cAMP levels, but steroids alone had little effect on bronchodilation in hPCLS. Bronchodilation induced by PGE2, CTX or forskolin was also augmented by simultaneous exposure to budesonide in hPCLS. Furthermore, HASM cells expressed membrane-bound glucocorticoid receptors that failed to translocate with glucocorticoid stimulation, and that potentially mediated the rapid effects of steroids on β2 agonist-induced bronchodilation. Knockdown of glucocorticoid receptor α had little effect on budesonide-induced and steroid-dependent augmentation of formoterol-induced cAMP generation in HASM. Collectively, these studies suggest that glucocorticoids amplify cAMP-dependent bronchodilation by directly increasing cAMP levels. These studies identify a molecular mechanism by which the combination of glucocorticoids and β2 agonists may augment bronchodilation in diseases such as asthma or chronic obstructive pulmonary disease

Magnetic Tower Outflows from a Radial Wire Array Z-pinch

We present the first results of high energy density laboratory astrophysics experiments which explore the evolution of collimated outflows and jets driven by a toroidal magnetic field. The experiments are scalable to astrophysical flows in that critical dimensionless numbers such as the Mach number, the plasma beta and the magnetic Reynolds number are all in the astrophysically appropriate ranges. Our experiments use the MAGPIE pulsed power machine and allow us to explore the role of magnetic pressure in creating and collimating the outflow as well as showing the creation of a central jet within the broader outflow cavity. We show that currents flow along this jet and we observe its collimation to be enhanced by the additional hoop stresses associated with the generated toroidal field. Although at later times the jet column is observed to go unstable, the jet retains its collimation. We also present simulations of the magnetic jet evolution using our two-dimensional resistive magneto-hydrodynamic (MHD) laboratory code. We conclude with a discussion of the astrophysical relevance of the experiments and of the stability properties of the jet.Comment: Accepted by MNRAS. 17 pages without figures. Full version with figures can be found at http://www.pas.rochester.edu/~afrank/labastro/MF230rv.pd

Analysis of radially resolved spectra and potential for lasing in Mo wire array Z pinches

Measurements of radially resolved L-shell Mo spectra from wire array pinches on Sandia's Z generator are presented and analyzed using a collisional-radiative model. The spectra indicate large radial gradients in density over the {approx}8-mm-diameter plasma column, but only the emission from the {approx}2 mm central region of the pinch appears to be influenced by opacity. Population inversions and significant gain factors for 100-200 {angstrom} transitions in Ne-like Mo are predicted to exist at the diagnosed plasma conditions

In vivo testing of novel vaccine prototypes against Actinobacillus pleuropneumoniae

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is a Gram-negative bacterium that represents the main cause of porcine pleuropneumonia in pigs, causing significant economic losses to the livestock industry worldwide. A. pleuropneumoniae, as the majority of Gram-negative bacteria, excrete vesicles from its outer membrane (OM), accordingly defined as outer membrane vesicles (OMVs). Thanks to their antigenic similarity to the OM, OMVs have emerged as a promising tool in vaccinology. In this study we describe the in vivo testing of several vaccine prototypes for the prevention of infection by all known A. pleuropneumoniae serotypes. Previously identified vaccine candidates, the recombinant proteins ApfA and VacJ, administered individually or in various combinations with the OMVs, were employed as vaccination strategies. Our data show that the addition of the OMVs in the vaccine formulations significantly increased the specific IgG titer against both ApfA and VacJ in the immunized animals, confirming the previously postulated potential of the OMVs as adjuvant. Unfortunately, the antibody response raised did not translate into an effective protection against A. pleuropneumoniae infection, as none of the immunized groups following challenge showed a significantly lower degree of lesions than the controls. Interestingly, quite the opposite was true, as the animals with the highest IgG titers were also the ones bearing the most extensive lesions in their lungs. These results shed new light on A. pleuropneumoniae pathogenicity, suggesting that antibody-mediated cytotoxicity from the host immune response may play a central role in the development of the lesions typically associated with A. pleuropneumoniae infections

Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 profile by activating the Th17 master regulator, STAT3, which in turn bound IL-17A and F promoters. Mitophagy-targeting siRNA failed to activate the Th17 profile. We conclude that metformin improves autophagy and mitochondrial function largely in parallel to ameliorate a newly defined inflammaging profile that echoes inflammation in diabetes

Antimicrobial susceptibility and genetic profile of Mycoplasma hyopneumoniae isolates from Brazil

Mycoplasma hyopneumoniae is the etiologic agent of porcine enzootic pneumonia, responsible for major production losses worldwide. The bacteria have a limited metabolism and need to obtain molecules from the growth environment, which causes multiple difficulties for in vitro culture. These limitations have a negative influence on the ability to carry out research for the development of the rational use of antimicrobials and vaccines. The objective of this investigation was to evaluate the genetic profile and in vitro susceptibility of field isolates of M. hyopneumoniae to different antimicrobials. All 16 isolates obtained from the samples presented 100% of identity in the partial sequence of 16S rRNA gene when compared to M. hyopneumoniae. A dendrogram was created using the PCR results of the genes related to pathogenicity, and the isolates were distributed into four clusters, suggesting genetic variability among four different isolates circulating on the same farm. The minimum inhibitory concentration of the isolates was higher for the antimicrobials tylosin (< 0.001–16 mg/L) and spiramycin (< 0.001–16 mg/L) than for enrofloxacin (< 0.001–0.125 mg/L) and tiamulin (< 0.001–0.125 mg/L). Our results demonstrate the genetic variability among M. hyopneumoniae isolates from pigs of the same farm, with differences in their susceptibility to antimicrobial agents

A Role for von Hippel-Lindau Protein in Pancreatic β-Cell Function

OBJECTIVE—The Vhlh gene codes for the von Hippel-Lindau protein (VHL), a tumor suppressor that is a key player in the cellular response to oxygen sensing. In humans, a germline mutation in the VHL gene leads to the von Hippel-Lindau disease, a familial syndrome characterized by benign and malignant tumors of the kidney, central nervous system, and pancreas