Longitudinal study of breastfeeding and growth in 0-6 month infants.

BACKGROUND AND OBJECTIVES: To explore advantages and challenges for exclusive breastfeeding (EBF), compared to non-exclusive breastfeeding (nEBF). METHODS AND STUDY DESIGN: Mothers from 7 cities in China were visited at 3, 10, 60, 120, and 180 days postpartum. Data about feeding practices, infant growth, and the macronutrient contents of human milk (HM) were collected. RESULTS: 130 lactating mothers attended 5 visits. 59 mothers (45.4%) exclusively breastfed infants for 0-4 month. Frequencies of breastfeeding per day were higher in the EBF group than the nEBF group at day 3, 10, 120 and 180, and were less than 8 times per day in the nEBF group. For Weight-for-age z scores, there were no differences between the two groups. Length-for-age z score was greater in the nEBF group at day 180 (0.74±1.05 vs 0.33±1.28). Weight-for-length z scores were greater in the EBF group at day 120 and 180 (day 120: 0.88±1.08 vs 0.36±1.1, day 180: 1.1±0.94 vs 0.54±1.07). The average protein and lactose contents of HM in the nEBF group were higher than in the EBF group at day 10. CONCLUSIONS: For nEBF infants, intake of formula replaced intake of breastmilk, due to lack of breastfeeding frequency, which did not bring weight gain for nEBF infants. During the introduction of complementary foods, EBF infants needed complementary nutrients to support growth. Therefore, lactating mothers may need to provide appropriate complementary feeding and maternal leave extension to attend to their infant's nutritional requirements. The criteria for linear growth may also need to be more commensurate with breastfeeding and relevant to later health outcomes.

Ubc9 mediates nuclear localization and growth suppression of BRCA1 and BRCA1a proteins.

BRCA1 gene mutations are responsible for hereditary breast and ovarian cancers. In sporadic breast tumors, BRCA1 dysfunction or aberrant subcellular localization is thought to be common. BRCA1 is a nuclear-cytoplasm shuttling protein and the reason for cytoplasmic localization of BRCA1 in young breast cancer patients is not yet known. We have previously reported BRCA1 proteins unlike K109R and cancer-predisposing mutant C61G to bind Ubc9 and modulate ER-α turnover. In the present study, we have examined the consequences of altered Ubc9 binding and knockdown on the subcellular localization and growth inhibitory function of BRCA1 proteins. Our results using live imaging of YFP, GFP, RFP-tagged BRCA1, BRCA1a and BRCA1b proteins show enhanced cytoplasmic localization of K109 R and C61G mutant BRCA1 proteins in normal and cancer cells. Furthermore, down-regulation of Ubc9 in MCF-7 cells using Ubc9 siRNA resulted in enhanced cytoplasmic localization of BRCA1 protein and exclusive cytoplasmic retention of BRCA1a and BRCA1b proteins. These mutant BRCA1 proteins were transforming and impaired in their capacity to inhibit growth of MCF-7 and CAL51 breast cancer cells. Interestingly, cytoplasmic BRCA1a mutants showed more clonogenicity in soft agar and higher levels of expression of Ubc9 than parental MCF7 cells. This is the first report demonstrating the physiological link between cytoplasmic mislocalization of mutant BRCA1 proteins, loss of ER-α repression, loss of ubiquitin ligase activity and loss of growth suppression of BRCA1 proteins. Thus, binding of BRCA1 proteins to nuclear chaperone Ubc9 provides a novel mechanism for nuclear import and control of tumor growth.