The clp chaperones and proteases of the human malaria parasite Plasmodium falciparum

The Clp chaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clp chaperones and proteases in the human malaria parasite Plasmodium falciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clp chaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.

Associations between dietary patterns at 6 and 15 months of age and sociodemographic factors

BACKGROUND/OBJECTIVES: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) have previously shown that dietary patterns are observable by 3 years. However, it is not clear when dietary patterns emerge. We aimed to describe dietary patterns in early life and their associations with maternal and infant sociodemographic characteristics.

SUBJECTS/METHODS: Principal component analysis was applied to diet questionnaires of ALSPAC participants at 6 months (n=7052) and 15 months (n=5610) to extract dietary patterns. The sociodemographic factors associated with dietary patterns were investigated using regression analyses.

RESULTS: Four dietary patterns were extracted at both 6 and 15 months. A traditional-style pattern characterized by home-prepared meats, vegetables and desserts, a second pattern characterized by ready-prepared baby foods and a third pattern characterized by discretionary foods such as biscuits, sweets and crisps were identified at both ages. At 6 months, the fourth pattern was characterized predominantly by breastfeeding and at 15 months, by contemporary-style foods including herbs, legumes, nuts, raw fruit and vegetables. Higher maternal age and education, number of siblings and lower body mass index (BMI) was associated with higher scores on the breastfeeding or meat, vegetables and desserts patterns, whereas higher discretionary food pattern scores were associated with younger maternal age, lower education, higher BMI and more siblings. Associations between sociodemographic factors and the ready-prepared baby food pattern scores were inconsistent across ages.

CONCLUSIONS: Dietary patterns emerge from infancy and are associated with sociodemographic characteristics.

Birthweight and childhood cancer : preliminary findings from the International Childhood Cancer Cohort Consortium (I4C)

BACKGROUND: Evidence relating childhood cancer to high birthweight is derived primarily from registry and case-control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium.

METHODS: We pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥4.0 vs. <4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort.

RESULTS: A linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre-pregnancy overweight or pregnancy weight gain. Birthweight ≥4.0 kg was associated with non-leukaemia cancer among children diagnosed at age ≥3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02].

CONCLUSION: Childhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to substantially modify these associations. Common factors underlying foetal growth and carcinogenesis need to be further explored.