Trefoil Factor 2 Negatively Regulates Type 1 Immunity against Toxoplasma gondii

IL-12-mediated type 1 inflammation confers host protection against the parasitic protozoan Toxoplasma gondii. However, production of IFN-γ, another type 1 inflammatory cytokine, also drives lethality from excessive injury to the intestinal epithelium. As mechanisms that restore epithelial barrier function following infection remain poorly understood, this study investigated the role of trefoil factor 2 (TFF2), a well-established regulator of mucosal tissue repair. Paradoxically, TFF2 antagonized IL-12 release from dendritic cells (DCs) and macrophages, which protected TFF2-deficient (TFF2(-/-)) mice from T. gondii pathogenesis. Dysregulated intestinal homeostasis in naive TFF2(-/-) mice correlated with increased IL-12/23p40 levels and enhanced T cell recruitment at baseline. Infected TFF2(-/-) mice displayed low rates of parasite replication and reduced gut immunopathology, whereas wild-type (WT) mice experienced disseminated infection and lethal ileitis. p38 MAPK activation and IL-12p70 production was more robust from TFF2(-/-)CD8(+) DC compared with WT CD8(+) DC and treatment of WT DC with rTFF2 suppressed TLR-induced IL-12/23p40 production. Neutralization of IFN-γ and IL-12 in TFF2(-/-) animals abrogated resistance shown by enhanced parasite replication and infection-induced morbidity. Hence, TFF2 regulated intestinal barrier function and type 1 cytokine release from myeloid phagocytes, which dictated the outcome of oral T. gondii infection in mice.     

Phylogenetic relationship and antifouling activity of bacterial epiphytes from the marine alga Ulva lactuca

It is widely accepted that bacterial epiphytes can inhibit the colonization of surfaces by common fouling organisms. However, little information is available regarding the diversity and properties of these antifouling bacteria. This study assessed the antifouling traits of five epiphytes of the common green alga, Ulva lactuca . All isolates were capable of preventing the settlement of invertebrate larvae and germination of algal spores. Three of the isolates also inhibited the growth of a variety of bacteria and fungi. Their phylogenetic positions were determined by 16S ribosomal subunit DNA sequencing. All isolates showed a close affiliation with the genus Pseudoalteromonas and, in particular, with the species P. tunicata . Strains of this bacterial species also display a variety of antifouling activities, suggesting that antifouling ability may be an important trait for members of this genus to be highly successful colonizers of animate surfaces and for such species to protect their host against fouling.     

Not all parents are the same: Diverse strategies of symbiont transmission in seaweeds

Different marine seaweed species have been shown to harbour specific bacterial communities, however, the extent to which vertical symbiont transmission from parents to offspring contributes to host-specificity is unclear. Here we use fluorescence and electron microscopy as well as 16S rRNA gene-based community analysis to investigate symbiont transmission in members of the three major seaweed groups (green Chlorophyta, red Rhodophyta and brown Phaeophyceae). We found seaweeds employ diverse strategies to transfer symbionts to their progeny. For instance, the green Ulva australis does not appear to have the capacity for vertical transmission. In contrast, the brown Phyllospora comosa adopts a non-selective vertical transmission. The red Delisea pulchra demonstrates weak selectivity in symbiont transmission, while the brown Hormosira banksii exhibits a strongly selective symbiont transfer. Mucilage on the gametes appears to facilitate vertical transmission and transferred bacteria have predicted properties that could support early development of the seaweeds. Previous meta-analysis has indicated that vertical transmission is rare in aquatic compared to terrestrial environments, however, our results contribute to the growing evidence that this might not be the case and that instead vertical transmission with various degrees of symbiont selection occurs in the ecologically important group of seaweeds.     

Inhibition of mammalian 5-lipoxygenase by aromatic disulfides

As a primary step in leukotriene biosynthesis, arachidonic acid is converted into 5-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid by 5-lipoxygenase. This enzyme is studied in the supernatant fraction from sonified RBL-1 cells, a preparation that converts [1-14C]arachidonic acid to 5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid and several 5,12-dihydroxyeicosatetraenoic acids including LTB4. In order to examine the reversibility of inhibitors, the supernatant fraction can be depleted of low molecular weight constituents by vacuum filtration. The 5-lipoxygenase is irreversibly inhibited by 500 microM N-ethyl-maleimide or 300 microM methyl methanethiolsulfonate, reagents that react covalently with protein sulfhydryl groups. In contrast, diphenyl disulfide reversibly inhibits this enzyme at 1-5 microM, irrespective of the GSH concentration in the supernatant. KCN also inhibits 5-lipoxygenase at 4 mM, suggesting the presence of a metal-containing prosthetic group. These observations imply that diphenyl disulfide and similar molecules with electron-releasing substituents on the aromatic rings could inhibit by binding to an electrophilic metallic center, the binding being stabilized by hydrophobic interactions between the enzyme and the aromatic groups on the flexible disulfide. Even though diphenyl disulfide does not inhibit soybean 15-lipoxygenase or endoperoxide synthase in cell-free systems, this compound does suppress prostaglandin as well as leukotriene synthesis in intact murine peritoneal macrophages and CXBG cells. Since lipoxygenases are susceptible to peroxide activation and peroxidase deactivation, changes in the redox state of the cell may alter arachidonic acid metabolism as effectively as actual enzyme inhibition.     

Disorders of the Menstrual Cycle in Elite Female Ice Hockey Players and Figure Skaters

The purpose of this study was to assess and compare the incidence of delayed menarche and menstrual dysfunction among elite ice hockey players and figure skaters. Forty-three ice hockey players (23.5 ± 4.8 years, 68.2 ± 1.2 kg, 1.68 ± 0.01 m) and 39 figure skaters (17.5 ± 3.4 years, 53.7 ± 5.8 kg, 1.64 ± 0.05 m) completed a self-administered questionnaire on their menstrual status and history, training regimens and lifestyle. Age at menarche did not differ significantly between ice hockey players (13.3 ± 1.3 years) and figure skaters (13.7 ± 1.4 years). Menarche was unrelated to nationality, vigorous training premenarche or age at which the athlete began her sport, but was correlated with the age at menarche of the athletes’ mothers (r = 0.39, p < 0.05). Hormonal contraceptives were used by 35% of ice hockey players and 15% of the figure skaters. Amenorrhea and oligomenorrhea were experienced by 7.1% and 38.7% of postmenarcheal, ice hockey players and figure skaters respectively not using hormonal contraceptives. Menstrual dysfunction was associated with both age and age at menarche in the ice hockey players only. Training factors, and psychological pressure were perceived by the athletes to contribute to menstrual dysfunction. A greater training volume, younger age at commencing sport, lower body mass, greater subjective body image pressure and younger biological and gynaecological age were reported among the figure skaters, and were proposed to explain the higher incidence of menstrual dysfunction among the figure skaters compared with the ice hockey players. Figure skaters appear at increased risk of amenorrhea and oligomenorrhea compared with ice hockey players, which may be linked to training and physical characteristics of the sports.