No abstract

Vitamin A deficiency (VAD) affects over 250 million people worldwide and is one of the most prevalent nutritional deficiencies in developing countries, resulting in significant socio-economic losses. Provitamin A carotenoids such as β-carotene, are derived from plant foods and are a major source of vitamin A for the majority of the world's population. Several years of intense research has resulted in the production of ‘Golden Rice 2’ which contains sufficiently high levels of provitamin A carotenoids to combat VAD. In this report, the focus is on the generation of transgenic maize with enhanced provitamin A content in their kernels. Overexpression of the bacterial genes crtB (for phytoene synthase) and crtI (for the four desaturation steps of the carotenoid pathway catalysed by phytoene desaturase and ζ-carotene desaturase in plants), under the control of a ‘super γ-zein promoter’ for endosperm-specific expression, resulted in an increase of total carotenoids of up to 34-fold with a preferential accumulation of β-carotene in the maize endosperm. The levels attained approach those estimated to have a significant impact on the nutritional status of target populations in developing countries. The high β-carotene trait was found to be reproducible over at least four generations. Gene expression analyses suggest that increased accumulation of β-carotene is due to an up-regulation of the endogenous lycopene β-cylase. These experiments set the stage for the design of transgenic approaches to generate provitamin A-rich maize that will help alleviate VAD.

BackgroundThe majority of breast cancer patients die of metastasis rather than primary tumors, whereas the molecular mechanisms orchestrating cancer metastasis remains poorly understood. Long noncoding RNAs (lncRNA) have been shown to regulate cancer occurrence and progression. However, the lncRNAs that drive metastasis in cancer patients and their underlying mechanisms are still largely unknown.MethodslncRNAs highly expressed in metastatic lymph nodes were identified by microarray. Survival analysis were made by Kaplan-Meier method. Cell proliferation, migration, and invasion assay was performed to confirm the phenotype of LINC02273. Tail vein model and mammary fat pad model were used for in vivo study. RNA pull-down and RIP assay were used to confirm the interaction of hnRNPL and LINC02273. Chromatin isolation by RNA purification followed by sequencing (ChIRP-seq), RNA-seq, ChIP-seq, and luciferase reporter assay reveal hnRNPL-LINC02273 regulates AGR2. Antisense oligonucleotides were used for in vivo treatment.ResultsWe identified a novel long noncoding RNA LINC02273, whose expression was significantly elevated in metastatic lesions compared to the primary tumors, by genetic screen of matched tumor samples. Increased LINC02273 promoted breast cancer metastasis in vitro and in vivo. We further showed that LINC02273 was stabilized by hnRNPL, a protein increased in metastatic lesions, in breast cancer cells. Mechanistically, hnRNPL-LINC02273 formed a complex which activated AGR2 transcription and promoted cancer metastasis. The recruitment of hnRNPL-LINC02273 complex to AGR2 promoter region epigenetically upregulated AGR2 by augmenting local H3K4me3 and H3K27ac levels. Combination of AGR2 and LINC02273 was an independent prognostic factor for predicting breast cancer patient survival. Moreover, our data revealed that LINC02273-targeting antisense oligonucleotides (ASO) substantially inhibited breast cancer metastasis in vivo.ConclusionsOur findings uncover a key role of LINC02273-hnRNPL-AGR2 axis in breast cancer metastasis and provide potential novel therapeutic targets for metastatic breast cancer intervention.

Objectives. We examined whether a home-based educational and environmental intervention delivered by lay health educators would improve asthma symptom control in inner-city children with asthma. Methods. Children 2 to 16 years of age with diagnosed asthma and at least 1 asthma-related hospitalization or 2 emergency visits in the prior year were randomly assigned into 2 groups (immediate and delayed intervention) in a crossover study. Each group participated in the active phase (intervention) and the inactive phase. Outcomes included asthma symptoms, albuterol use, emergency department visits, hospitalizations, and trigger reduction. Results. A total of 264 primarily Black (94%) children were enrolled. The mean number of emergency visits decreased by 30% and inpatient visits decreased by 53% (P < .001) after the intervention. Reductions were seen in pests, presence of carpets in bedrooms, and dust. Nighttime wheezing was significantly reduced after the intervention in both groups (P < .001). Conclusions. Lay health educators effectively reduced asthma triggers and increased caregiver asthma knowledge, which resulted in reduced emergency department visits, hospitalizations, and asthma symptoms. The relationships formed between the caregivers and the lay health educators appeared to positively impact asthma outcomes in this disadvantaged population.