Iodine-fortified toddler milk improves dietary iodine intakes and iodine status in toddlers: a randomised controlled trial.

PURPOSE: We aimed to evaluate the effectiveness of consuming iodine-fortified toddler milk for improving dietary iodine intakes and biochemical iodine status in toddlers. METHODS: In a 20-week parallel randomised controlled trial, healthy 12-20-month-old children were assigned to: Fortified Milk [n = 45; iodine-fortified (21.1 µg iodine/100 g prepared drink) cow's milk], or Non-Fortified Milk (n = 90; non-fortified cow's milk). Food and nutrient intakes were assessed with 3-day weighed food records at baseline, and weeks 4 and 20. Urinary iodine concentration (UIC) was measured at baseline and 20 weeks. RESULTS: At baseline, toddlers' median milk intake was 429 g/day. There was no evidence that milk intakes changed within or between the groups during the intervention. Toddlers' baseline geometric mean iodine intake was 46.9 µg/day, and the median UIC of 43 µg/L in the Fortified Milk group and 55 µg/L in the Non-Fortified Milk group indicated moderate and mild iodine deficiency, respectively, with this difference due to chance. During the intervention, iodine intakes increased by 136% (p < 0.001) and UIC increased by 85 µg/L (p < 0.001) in the Fortified Milk group compared to the Non-Fortified Milk group. The 20-week median UIC was 91 µg/L in the Fortified Milk group and 49 µg/L in the Non-Fortified Milk group. CONCLUSIONS: Consumption of ≈ 1.7 cups of iodine-fortified toddler milk per day for 20 weeks can increase dietary iodine intakes and UIC in healthy iodine-deficient toddlers. This strategy alone is unlikely to provide sufficient intake to ensure adequate iodine status in toddlers at risk of mild-to-moderate iodine deficiency.

The RtcB RNA ligase is an essential component of the metazoan unfolded protein response.

RNA ligation can regulate RNA function by altering RNA sequence, structure and coding potential. For example, the function of XBP1 in mediating the unfolded protein response requires RNA ligation, as does the maturation of some tRNAs. Here, we describe a novel in vivo model in Caenorhabditis elegans for the conserved RNA ligase RtcB and show that RtcB ligates the xbp-1 mRNA during the IRE-1 branch of the unfolded protein response. Without RtcB, protein stress results in the accumulation of unligated xbp-1 mRNA fragments, defects in the unfolded protein response, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves, and RtcB mutants have defects in growth and lifespan that can be bypassed by expression of pre-spliced tRNAs. In addition, animals that lack RtcB have defects that are independent of tRNA maturation and the unfolded protein response. Thus, RNA ligation by RtcB is required for the function of multiple endogenous target RNAs including both xbp-1 and tRNAs. RtcB is uniquely capable of performing these ligation functions, and RNA ligation by RtcB mediates multiple essential processes in vivo.

Syndecan promotes axon regeneration by stabilizing growth cone migration.

Growth cones facilitate the repair of nervous system damage by providing the driving force for axon regeneration. Using single-neuron laser axotomy and in vivo time-lapse imaging, we show that syndecan, a heparan sulfate (HS) proteoglycan, is required for growth cone function during axon regeneration in C. elegans. In the absence of syndecan, regenerating growth cones form but are unstable and collapse, decreasing the effective growth rate and impeding regrowth to target cells. We provide evidence that syndecan has two distinct functions during axon regeneration: (1) a canonical function in axon guidance that requires expression outside the nervous system and depends on HS chains and (2) an intrinsic function in growth cone stabilization that is mediated by the syndecan core protein, independently of HS. Thus, syndecan is a regulator of a critical choke point in nervous system repair.

In vivo laser axotomy in C. elegans.

Neurons communicate with other cells via axons and dendrites, slender membrane extensions that contain pre- or post-synaptic specializations. If a neuron is damaged by injury or disease, it may regenerate. Cell-intrinsic and extrinsic factors influence the ability of a neuron to regenerate and restore function. Recently, the nematode C. elegans has emerged as an excellent model organism to identify genes and signaling pathways that influence the regeneration of neurons(1-6). The main way to initiate neuronal regeneration in C. elegans is laser-mediated cutting, or axotomy. During axotomy, a fluorescently-labeled neuronal process is severed using high-energy pulses. Initially, neuronal regeneration in C. elegans was examined using an amplified femtosecond laser(5). However, subsequent regeneration studies have shown that a conventional pulsed laser can be used to accurately sever neurons in vivo and elicit a similar regenerative response(1,3,7). We present a protocol for performing in vivo laser axotomy in the worm using a MicroPoint pulsed laser, a turnkey system that is readily available and that has been widely used for targeted cell ablation. We describe aligning the laser, mounting the worms, cutting specific neurons, and assessing subsequent regeneration. The system provides the ability to cut large numbers of neurons in multiple worms during one experiment. Thus, laser axotomy as described herein is an efficient system for initiating and analyzing the process of regeneration.