Dietary Supplementation with Ethyl Ester Concentrates of Fish Oil (n-3) and Borage Oil (n-6) Polyunsaturated Fatty Acids Induces Epidermal Generation of Local Putative Anti-Inflammatory Metabolites

Clinical reports have attributed the amelioration of chronic inflammatory skin disorders to the presence of certain polyunsaturated fatty acids (PUFA) in dietary oils. To test the hypothesis of a local modulatory effect of these PUFA in the epidermis, the basal diet of normal guinea pigs was supplemented with ethyl esters of either fish oil [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] or borage oi1 [rich in gamma-linolenic acid (GLA)]. Our data demonstrated that dietary oils influence the distribution of PUFA in epidermal phospholipids and the epidermal levels of PUFA-derived hydroxy fatty acids. Specifically, animals supplemented with ethyl esters of fish oil markedly incorporated EPA and DHA into epidermal phospholipids, which paralleled the epidermal accumulation of 1 5-hydroxyeicosapentaenoic acid (15-HEPE) and 17-hydroxydocosahexaenoic acid (17-HDoHE). Similarly, animals supplemented with esters of borage oil preferentially incorporated dihomogammalinolenic acid (DGLA), the epidermal elongase product of GLA, into the epidermal phospholipids, which also was ac- companied by epidermal accumulation of 15-hydroxyeicosatrienoic acid (15-HETrE). By factoring the epidermal levels of the 15-lipoxygenase products and their relative inhibitory potencies, we evolved a measure of the overall potential of dietary oils to exert local anti-inflammatory effect. For example, the leukotriene inhibition potentials (LIP) of both fish oil and borage oil were greatly enhanced when compared to controls. Thus, the altered profiles of epidermal 15-lipoxygenase products generated from particular dietary oils may be responsible, at least in part, for reported ameliorative effects of oils on chronic inflammatory skin disorders

Substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza A H3N2 viruses in U.S. swine

Swine influenza A virus is an endemic and economically important pathogen in pigs, with the potential to infect other host species. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major component in swine influenza A vaccines. However, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. Characterizing the cross-reactivity between strains in pigs and seasonal influenza virus strains in humans is also important in assessing the relative risk of interspecies transmission of viruses from one host population to the other. Hemagglutination inhibition (HI) assay data for swine and human H3N2 viruses were used with antigenic cartography to quantify the antigenic differences among H3N2 viruses isolated from pigs in the United States from 1998 to 2013 and the relative cross-reactivity between these viruses and current human seasonal influenza A virus strains. Two primary antigenic clusters were found circulating in the pig population, but with enough diversity within and between the clusters to suggest updates in vaccine strains are needed. We identified single amino acid substitutions that are likely responsible for antigenic differences between the two primary antigenic clusters and between each antigenic cluster and outliers. The antigenic distance between current seasonal influenza virus H3 strains in humans and those endemic in swine suggests that population immunity may not prevent the introduction of human viruses into pigs, and possibly vice versa, reinforcing the need to monitor and prepare for potential incursions

A cyclic-di-GMP receptor required for bacterial exopolysaccharide production

Bis-(3′,5′)-cyclic-dimeric-guanosine monophosphate (c-di-GMP) has been shown to be a global regulatory molecule that modulates the reciprocal responses of bacteria to activate either virulence pathways or biofilm formation. The mechanism of c-di-GMP signal transduction, including recognition of c-di-GMP and subsequent phenotypic regulation, remain largely uncharacterized. The key components of these regulatory pathways are the various adaptor proteins (c-di-GMP receptors). There is compelling evidence suggesting that, in addition to PilZ domains, there are other unidentified c-di-GMP receptors. Here we show that the PelD protein of Pseudomonas aeruginosa is a novel c-di-GMP receptor that mediates c-di-GMP regulation of PEL polysaccharide biosynthesis. Analysis of PelD orthologues identified a number of conserved residues that are required for c-di-GMP binding as well as synthesis of the PEL polysaccharide. Secondary structure similarities of PelD to the inhibitory site of diguanylate cyclase suggest that a common fold can act as a platform to bind c-di-GMP. The combination of a c-di-GMP binding site with a variety of output signalling motifs within one protein domain provides an explanation for the specificity for different cellular responses to this regulatory dinucleotide

Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses

Citation: Balzli, C., Lager, K., Vincent, A., Gauger, P., Brockmeier, S., Miller, L., . . . Swayne, D. E. (2016). Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses. Influenza and other Respiratory Viruses. doi:10.1111/irv.12386Background: The ability of pigs to become infected with low pathogenic avian influenza (LPAI) viruses and then generate mammalian adaptable influenza A viruses is difficult to determine. Yet, it is an important link to understanding any relationship between LPAI virus ecology and possible epidemics among swine and/or humans. Objectives: Assess susceptibility of pigs to LPAI viruses found within the United States and their direct contact transmission potential. Methods: Pigs were inoculated with one of ten H5 or H7 LPAI viruses selected from seven different bird species to test infectivity, virulence, pathogenesis, and potential to transmit virus to contact pigs through histological, RRT-PCR and seroconversion data. Results: Although pigs were susceptible to infection with each of the LPAI viruses, no clinical disease was recognized in any pig. During the acute phase of the infection, minor pulmonary lesions were found in some pigs and one or more pigs in each group were RRT-PCR-positive in the lower respiratory tract, but no virus was detected in upper respiratory tract (negative nasal swabs). Except for one group, one or more pigs in each LPAI group developed antibody. No LPAI viruses transmitted to contact pigs. Conclusions: LPAI strains from various bird populations within the United States are capable of infecting pigs. Although adaptability and transmission of individual strains seem unlikely, the subclinical nature of the infections demonstrates the need to improve sampling and testing methods to more accurately measure incidence of LPAI virus infection in pigs, and their potential role in human-zoonotic LPAI virus dynamics. © 2016 John Wiley & Sons Ltd

A Statistical Mechanical Problem in Schwarzschild Spacetime

We use Fermi coordinates to calculate the canonical partition function for an ideal gas in a circular geodesic orbit in Schwarzschild spacetime. To test the validity of the results we prove theorems for limiting cases. We recover the Newtonian gas law subject only to tidal forces in the Newtonian limit. Additionally we recover the special relativistic gas law as the radius of the orbit increases to infinity. We also discuss how the method can be extended to the non ideal gas case.Comment: Corrected an equation misprint, added four references, and brief comments on the system's center of mass and the thermodynamic limi

Process mapping strategies to prevent subcutaneous implantable cardioverter-defibrillator infections

Background: Infection remains a major complication of cardiac implantable electronic devices and can lead to significant morbidity and mortality. Implantable devices that avoid transvenous leads, such as the subcutaneous implantable cardioverter-defibrillator (S-ICD), can reduce the risk of serious infection-related complications, such as bloodstream infection and infective endocarditis. While the 2017 AHA/ACC/HRS guidelines include recommendations for S-ICD use for patients at high risk of infection, currently, there are no clinical trial data that address best practices for the prevention of S-ICD infections. Therefore, an expert panel was convened to develop a consensus on these topics. Methods: An expert process mapping methodology was used to achieve consensus on the appropriate steps to minimize or prevent S-ICD infections. Two face-to-face meetings of high-volume S-ICD implanters and an infectious diseases specialist, with expertise in cardiovascular implantable electronic device infections, were conducted to develop consensus on useful strategies pre-, peri-, and postimplant to reduce S-ICD infection risk. Results: Expert panel consensus on recommended steps for patient preparation, S-ICD implantation, and postoperative management was developed to provide guidance in individual patient management. Conclusion: Achieving expert panel consensus by process mapping methodology for S-ICD infection prevention was attainable, and the results should be helpful to clinicians in adopting interventions to minimize risks of S-ICD infection

Segregation by Racial and Demographic Group: Evidence from the San Francisco Bay Area

This paper considers residential segregation by race and by type of household in 1970 and 1980. The paper presents entropy indices of segregation for the San Francisco Bay Area and its five metropolitan areas. The methodology permits an investigation of the effects of group definition upon segregation measures, and an analysis of the degree of independence in the segregation of households by race and demographic group. The results indicate that the levels of segregation by race and by household type have declined modestly during the 1970s, at least in this region. More importantly, however, the results indicate a remarkable independence in the spatial distribution of households by race and demographic group. Only a very small fraction of the observed levels of segregation by race could be ’explained’ by the prior partitioning of households by demographic group. The principal results of the analysis are invariant to changes in the definition of racial or household groups

Growing dynamical length, scaling and heterogeneities in the 3d Edwards-Anderson model

We study numerically spatio-temporal fluctuations during the out-of-equilibrium relaxation of the three-dimensional Edwards-Anderson model. We focus on two issues. (1) The evolution of a growing dynamical length scale in the glassy phase of the model, and the consequent collapse of the distribution of local coarse-grained correlations measured at different pairs of times on a single function using {\it two} scaling parameters, the value of the global correlation at the measuring times and the ratio of the coarse graining length to the dynamical length scale (in the thermodynamic limit). (2) The `triangular' relation between coarse-grained local correlations at three pairs of times taken from the ordered instants $t_3 \leq t_2 \leq t_1$. Property (1) is consistent with the conjecture that the development of time-reparametrization invariance asymptotically is responsible for the main dynamic fluctuations in aging glassy systems as well as with other mechanisms proposed in the literature. Property (2), we stress, is a much stronger test of the relevance of the time-reparametrization invariance scenario.Comment: 24 pages, 12 fig

ruvA Mutants that resolve Holliday junctions but do not reverse replication forks

RuvAB and RuvABC complexes catalyze branch migration and resolution of Holliday junctions (HJs) respectively. In addition to their action in the last steps of homologous recombination, they process HJs made by replication fork reversal, a reaction which occurs at inactivated replication forks by the annealing of blocked leading and lagging strand ends. RuvAB was recently proposed to bind replication forks and directly catalyze their conversion into HJs. We report here the isolation and characterization of two separation-of-function ruvA mutants that resolve HJs, based on their capacity to promote conjugational recombination and recombinational repair of UV and mitomycin C lesions, but have lost the capacity to reverse forks. In vivo and in vitro evidence indicate that the ruvA mutations affect DNA binding and the stimulation of RuvB helicase activity. This work shows that RuvA's actions at forks and at HJs can be genetically separated, and that RuvA mutants compromised for fork reversal remain fully capable of homologous recombination