Phase-Variable Changes in the Position of O-Methyl Phosphoramidate Modifications on the Polysaccharide Capsule of Campylobacter jejuni Modulate Serum Resistance.

Campylobacter jejuni polysaccharide capsules (CPS) are characterized by the presence of nonstoichiometric O-methyl phosphoramidate (MeOPN) modifications. The lack of stoichiometry is due to phase variation at homopolymeric tracts within the MeOPN transferase genes. C. jejuni strain 81-176 contains two MeOPN transferase genes and has been shown previously to contain MeOPN modifications at the 2 and 6 positions of the galactose (Gal) moiety in the CPS. We demonstrate here that one of the two MeOPN transferases, encoded by CJJ81176_1435, is bifunctional and is responsible for the addition of MeOPN to both the 2 and the 6 positions of Gal. A new MeOPN at the 4 position of Gal was observed in a mutant lacking the CJJ81176_1435 transferase and this was encoded by the CJJ81176_1420 transferase. During routine growth of 81-176, the CJJ81176_1420 transferase was predominantly in an off configuration, while the CJJ81176_1435 transferase was primarily on. However, exposure to normal human serum selected for cells expressing the CJJ81176_1420 transferase. MeOPN modifications appear to block binding of naturally occurring antibodies to the 81-176 CPS. The absence of MeOPN-4-Gal resulted in enhanced sensitivity to serum killing, whereas the loss of MeOPN-2-Gal and MeOPN-6-Gal resulted in enhanced resistance to serum killing, perhaps by allowing more MeOPN to be put onto the 4 position of Gal.IMPORTANCECampylobacter jejuni undergoes phase variation in genes encoding surface antigens, leading to the concept that a strain of this organism consists of multiple genotypes that are selected for fitness in various environments. Methyl phosphoramidate modifications on the capsule of C. jejuni block access of preexisting antibodies in normal human sera to the polysaccharide chain, thus preventing activation of the classical arm of the complement cascade. We show that the capsule of strain 81-176 contains more sites of MeOPN modifications than previously recognized and that one site, on the 4 position of galactose, is more critical to complement resistance than the others. Exposure to normal human serum selects for variants in the population expressing this MeOPN modification.

The polysaccharide capsule of Campylobacter jejuni modulates the host immune response.

Campylobacter jejuni is a major cause of bacterial diarrheal disease worldwide. The organism is characterized by a diversity of polysaccharide structures, including a polysaccharide capsule. Most C. jejuni capsules are known to be decorated nonstoichiometrically with methyl phosphoramidate (MeOPN). The capsule of C. jejuni 81-176 has been shown to be required for serum resistance, but here we show that an encapsulated mutant lacking the MeOPN modification, an mpnC mutant, was equally as sensitive to serum killing as the nonencapsulated mutant. A nonencapsulated mutant, a kpsM mutant, exhibited significantly reduced colonization compared to that of wild-type 81-176 in a mouse intestinal colonization model, and the mpnC mutant showed an intermediate level of colonization. Both mutants were associated with higher levels of interleukin 17 (IL-17) expression from lamina propria CD4(+) cells than from cells from animals infected with 81-176. In addition, reduced levels of Toll-like receptor 4 (TLR4) and TLR2 activation were observed following in vitro stimulation of human reporter cell lines with the kpsM and mpnC mutants compared to those with wild-type 81-176. The data suggest that the capsule polysaccharide of C. jejuni and the MeOPN modification modulate the host immune response.

Mindfulness and its relationship to emotional regulation.

Research on the effectiveness and mechanisms of mindfulness training applied in psychotherapy is still in its infancy (Erisman & Roemer, 2010). For instance, little is known about the extent and processes through which mindfulness practice improves emotion regulation. This experience sampling study assessed the relationship between mindfulness, emotion differentiation, emotion lability, and emotional difficulties. Young adult participants reported their current emotional experiences 6 times per day during 1 week on a PalmPilot device. Based on these reports of emotions, indices of emotional differentiation and emotion lability were composed for negative and positive emotions. Mindfulness was associated with greater emotion differentiation and less emotional difficulties (i.e., emotion lability and self-reported emotion dysregulation). Mediational models indicated that the relationship between mindfulness and emotion lability was mediated by emotion differentiation. Furthermore, emotion regulation mediated the relationship between mindfulness and both negative emotion lability and positive emotion differentiation. This experience sampling study indicates that self-reported levels of mindfulness are related to higher levels of differentiation of one's discrete emotional experiences in a manner reflective of effective emotion regulation.

Coping in parents of schizophrenia patients with differing degrees of familial exposure to psychosis.

Over the past 50 years, parents have become more involved in the care of their schizophrenic sons and daughters. Although such responsibility can be gratifying, parents frequently report feeling burdened and distressed. These feelings may affect parents' coping strategies in times of stress. This study examined the effects of family history of psychosis on coping styles in parents of patients. Coping strategies of parents with and without additional first-degree relatives suffering from psychosis (besides the index son or daughter) and controls were compared. As predicted, more family history of psychosis was negatively related to coping ability in parents. Findings suggest that greater familial exposure to psychosis may have an adverse effect on their ability to deal with life stressors. Results are discussed in light of the possible influence of genetic and environmental factors.