Publications

Interferon-induced proteins, including the largely uncharacterized interferon-induced tetratricopeptide repeat (IFIT) protein family, provide defenses against pathogens. Differing from expectations for tetratricopeptide repeat (TPR) proteins and from human IFIT1, IFIT2, and IFIT3, we show that human IFIT5 recognizes cellular RNA instead of protein partners. In vivo and in vitro, IFIT5 bound to endogenous 5'-phosphate-capped RNAs, including transfer RNAs. The crystal structure of IFIT5 revealed a convoluted intramolecular packing of eight TPRs as a fold that we name the TPR eddy. Additional, non-TPR structural elements contribute to an RNA binding cleft. Instead of general cytoplasmic distribution, IFIT5 concentrated in actin-rich protrusions from the apical cell surface colocalized with the RNA-binding retinoic acid-inducible gene-I (RIG-I). These findings establish compartmentalized cellular RNA binding activity as a mechanism for IFIT5 function and reveal the TPR eddy as a scaffold for RNA recognition.

OBJECTIVE

To determine the association of beverage consumption with obesity in Mexican American school-aged children.

DESIGN

Cross-sectional study using the baseline data from a cohort study. Mothers and children answered questions about the frequency and quantity of the child's consumption of soda, diet soda, other sugar-sweetened beverages, 100% fruit juice, milk and water. The questions were adapted from the Youth/Adolescent FFQ. Children were weighed and measured. Data were collected on the following potential confounders: maternal BMI, household income, maternal education, maternal occupational status, maternal acculturation, child physical activity, child screen time and child fast-food consumption. Logistic regression was used to examine the association between servings (240 ml) of each beverage per week and obesity (BMI ≥ 95th percentile).

SETTING

Participants were recruited from among enrolees of the Kaiser Permanente Health Plan of Northern California. Data were collected via an in-home assessment.

SUBJECTS

Mexican American children (n 319) aged 8-10 years.

RESULTS

Among participants, 20% were overweight and 31% were obese. After controlling for potential confounders, consuming more servings of soda was associated with increased odds of obesity (OR = 1·29; P < 0·001). Consuming more servings of flavoured milk per week was associated with lower odds of obesity (OR = 0·88; P = 0·004). Consumption of other beverages was not associated with obesity in the multivariate model.

CONCLUSIONS

Discouraging soda consumption among Mexican American children may help reduce the high obesity rates in this population.

The impact of non-neurological and metabolic side effects (NNSEs) on the prescription of antipsychotics in real clinical practice remains unclear. We conducted an intention-to-treat, secondary analysis of data from a randomised, controlled trial (CUtLASS-1; n=227) to examine NNSEs emergent at 12 weeks and 52 weeks. A clinically significant difference was defined as double or half the symptoms in groups prescribed first- versus second-generation antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for first-generation drugs) or less than 0.5 (indicating advantage for the newer drugs). There were no differences between the treatment groups at baseline. At both 12 and 52 weeks follow-up, patients on second-generation drugs were more likely than their first-generation counterparts to experience cardiovascular problems and anticholinergic side effects, as well as increased sexual side effects in men. Objective weight gain was equivalent between the two groups at 12 weeks, but by one year fewer patients in the second-generation arm experienced weight gain and there was no significant difference with regard to percent change in BMI. These results suggest that there may be clinically significant increases in anticholinergic, cardiovascular, and sexual side effects for patients on second-generation drugs. The expected increased weight gain in the second-generation arm did not occur. This study provides evidence that clinicians should take a more nuanced approach toward expert antipsychotic prescription, rather than viewing the drugs as distinct classes.

Tumours evolve several mechanisms to evade apoptosis, yet many resected carcinomas show significantly elevated caspase activity. Moreover, caspase activity is positively correlated with tumour aggression and adverse patient outcome. These observations indicate that caspases might have a functional role in promoting tumour invasion and metastasis. Using a Drosophila model of invasion, we show that precise effector caspase activity drives cell invasion without initiating apoptosis. Affected cells express the matrix metalloprotinase Mmp1 and invade by activating Jnk. Our results link Jnk and effector caspase signalling during the invasive process and suggest that tumours under apoptotic stresses from treatment, immune surveillance or intrinsic signals might be induced further along the metastatic cascade.