PLD3 and PLD4 are single-stranded acid exonucleases that regulate endosomal nucleic-acid sensing.

The sensing of microbial genetic material by leukocytes often elicits beneficial pro-inflammatory cytokines, but dysregulated responses can cause severe pathogenesis. Genome-wide association studies have linked the gene encoding phospholipase D3 (PLD3) to Alzheimer's disease and have linked PLD4 to rheumatoid arthritis and systemic sclerosis. PLD3 and PLD4 are endolysosomal proteins whose functions are obscure. Here, PLD4-deficient mice were found to have an inflammatory disease, marked by elevated levels of interferon-γ (IFN-γ) and splenomegaly. These phenotypes were traced to altered responsiveness of PLD4-deficient dendritic cells to ligands of the single-stranded DNA sensor TLR9. Macrophages from PLD3-deficient mice also had exaggerated TLR9 responses. Although PLD4 and PLD3 were presumed to be phospholipases, we found that they are 5' exonucleases, probably identical to spleen phosphodiesterase, that break down TLR9 ligands. Mice deficient in both PLD3 and PLD4 developed lethal liver inflammation in early life, which indicates that both enzymes are needed to regulate inflammatory cytokine responses via the degradation of nucleic acids.

Impact of the Swap It, Don't Stop It Australian National Mass Media Campaign on Promoting Small Changes to Lifestyle Behaviors.

Mass media campaigns aimed at influencing lifestyle risk factors are one way that governments are attempting to address chronic disease risk. In Australia, a national campaign aimed at encouraging Australians to make changes in lifestyle-related behaviors was implemented from 2008 to 2011. The first phase, Measure Up (2008-2009), focused on why lifestyle changes are needed by increasing awareness of the link between waist circumference and chronic disease risk. The second phase, Swap It, Don't Stop It (2011), emphasized how adults can change their behaviors. Cross-sectional telephone surveys (after the campaign) were undertaken in July and November 2011 to evaluate the Swap It, Don't Stop It campaign and included measures of campaign awareness and lifestyle-related behavior change. Survey participants (N = 5,097) were similar across the two survey periods. Prompted campaign awareness was 62% (16% for unprompted awareness); females, younger respondents (18-44 years), those in paid employment, and those who spoke English at home were more likely to report prompted/unprompted campaign awareness. Moreover, 16% of survey respondents reported any swapping behavior in the previous 6 months, with the majority (14%) reporting only one swap; younger respondents and those in paid employment were significantly more likely to report having implemented a swapping behavior. The campaign achieved modest population awareness but demonstrated limited effect in terms of nudging behaviors. This evaluation indicates that encouraging swapping behaviors as a prelude to lifestyle change may not result from a mass media campaign alone; a comprehensive multicomponent population approach may be required.

Getting the message across: outcomes and risk profiles by awareness levels of the "measure-up" obesity prevention campaign in Australia.

BACKGROUND: Obesity campaign evaluations have used campaign awareness to assess impact, yet have not compared unprompted campaign recallers, with prompted recallers and those with no campaign recall. Using data from an Australian mass-media obesity prevention campaign linking waist circumference and chronic disease we examined whether those with different degrees of campaign recall are distinct groups demographically and for subsequent campaign effects. METHODS: A national cross-sectional telephone survey of randomly selected adults aged 18 to 65 years was conducted post- campaign (n = 2812) covering campaign recall, self-reported diet and physical activity (PA) and waist-measuring knowledge, behaviours and intentions to make lifestyle changes. Respondents were divided into three groups indicating campaign recall: Unprompted Recallers (n=1154); Prompted Recallers (n=1284); and No Recallers (n=374) and compared on demographic, knowledge, and behavioural risk factors for obesity/chronic disease. RESULTS: Unprompted Recallers were more likely to speak English at home (p<.001), be in the primary campaign target group (25-45 years with children) (p<0.001) than the other two groups and to be university educated and female than the Prompted Recall group only (p=0.001). Unprompted Recallers had better knowledge about recommended waist circumference (p<.001), fruit (p=0.004), vegetable (p<0.001) and PA guidelines (p<0.001) than both the other groups. The No Recall group was less likely than the other two to be overweight/obese (46% vs 55%, p=0.020 and 54%, p=0.037), comparable on meeting fruit consumption and PA guidelines but more likely to meet vegetable intake recommendations (than Unprompted Recallers only). CONCLUSIONS: Unprompted recallers were more knowledgeable about campaign messages; behaviour change and intentions to change were stronger for the two recall groups compared with the No Recall group but not different between them. The current analysis revealed subtle differences in campaign exposure and/or attendance by different demographic subgroups that would not be apparent in a simple aware/unaware dichotomy.

Sibling conflict in middle childhood predicts children's adjustment in early adolescence.

Associations between sibling conflict in middle childhood and psychological adjustment in early adolescence were studied in a sample of 80 boys and 56 girls. Parents and children provided self-report data about family relationships and children's adjustment. Parents' hostility to children was assessed from videotaped interactions. Results showed that sibling conflict at Time 1 predicted increases in children's anxiety, depressed mood, and delinquent behavior 2 years later. Moreover, earlier sibling conflict at Time 1 accounted for unique variance in young adolescents' Time 2 anxiety, depressed mood, and delinquent behavior above and beyond the variance explained by earlier maternal hostility and marital conflict. Children's adjustment at Time 1 did not predict sibling conflict at Time 2. Results highlight the unique significance of the earlier sibling relationship for young adolescents' psychological adjustment.