The link to dietary protein quality is

The link to dietary protein quality is of particular interest from a public health lens; as the authors note, “dietary intake of essential order Paclitaxel may be insufficient in children with stunting”. Previous research supports this hypothesis: An analysis of dietary and anthropometric data collected on Ghanaian children aged 2–13years, found an association between dietary protein inadequacy (adjusting for quality) and risk of being stunted (). A meta-analysis of consumption of conventional versus quality protein maize (higher in lysine and tryptophan) showed significantly higher rates of weight and height gain among young children with mild to moderate undernutrition from populations in which maize is the major staple food (). Additionally, an analysis of national food balance sheet data from developing countries found an inverse association between rates of stunting and the per capita availability of “utilizable” protein (adjusted for quality) but not total protein (). Finally, the authors conclude, “randomized controlled trials would ultimately be required to determine whether essential amino acids…play a causal role in the pathogenesis of child stunting”. We whole-heartedly agree with this statement and point to some interesting findings emerging from an RCT recently completed in Ghana (). This trial examined the effect of adding a protein quality and micronutrient-improved complementary food supplement to the diets of Ghanaian infants from age 6 to 18months. Results show a dose response effect of receiving the supplement on HAZ scores at 18months of age (unpublished). Biomarkers of inflammation, micronutrient status, and plasma amino acids were collected as well. We look forward to presenting the findings of this longitudinal analyses in comparison with the cross sectional association of stunting and amino acids as observed by Semba et al.
Introduction Cancer comprises a collection of complex genetic and epigenetic diseases that arise through multistep processes (Tallen and Riabowol, 2014). Tumor cells acquire common properties, including unlimited proliferation potential, self-sufficiency in growth signaling, neovascularization for nutrient and oxygen supply, and resistance to anti-proliferative and apoptotic stimuli (Hanahan and Weinberg, 2011). In resting cells, the cell cycle is strictly managed by a set of regulatory proteins that control the various cell cycle checkpoints (Collado et al., 2007; Collins et al., 1997). This cell cycle machinery is often deregulated in cancer as a consequence of the silencing of various tumor suppressor genes (Collins et al., 1997; Tallen and Riabowol, 2014). In fact, loss of tumor suppressor genes and their encoded proteins through deletion, inactivating mutations, epigenetic silencing or post-translational modification results in tumorigenesis. The progression of the mammalian cell cycle from G1 to mitosis is regulated by various cyclin proteins and their catalytic subunits referred to as cyclin-dependent kinases (CDKs) (Nabel, 2002). A family of cyclin–CDK inhibitor proteins (CDIs), which bind and inactivate the CDKs, has been isolated. This family includes the p16INK4a, p21CIP1, p27KIP1, and associated proteins p15INK4b, p18INK4c, p19INK4d and p57KIP2 (Nabel, 2002). These proteins potentially act as tumor suppressors and their inactivation corresponds with human carcinogenesis. One of the tumor suppressor proteins that is inactivated in cancer is the p16INK4a protein, which is encoded by the cyclin-dependent kinase inhibitor 2A (CDKN2A) or multiple tumor suppressor 1 (MTS1) gene (Fig. 1) (Witcher and Emerson, 2009). The CDKN2A gene is located within the frequently deleted chromosomal region 9 of p21 (Gil and Peters, 2006). This gene (8.5kb full length) contains two introns and three exons and encodes the p16INK4a protein. The p16INK4a protein is a protein consisting of 156 amino acids with a molecular weight of 16kDa and is a negative regulator of the cell cycle (Serrano et al., 1993). In addition to p16INK4a, CDKN2A encodes a completely unrelated tumor suppressor protein, alternate open reading frame (ARF or p19Arf in mice), which interacts with the p53 regulatory protein, mouse double minute 2 homolog (MDM2) (Pomerantz et al., 1998). The simple tandem arrangement is complicated by the presence of an additional exon 1β, which is transcribed from its own promoter. The resulting RNA incorporates exons 2 and 3, but specifies a distinct protein because the exons are translated by an alternative reading frame. Thus, while exons 2 and 3 are shared by the two mRNAs, they encode different protein products, p16INK4a and ARF (Quelle et al., 1995). The specific binding of the p16INK4a protein to CDK4 or CDK6 induces an allosteric conformational change in these proteins and inhibits the formation of the complex between CDK4 or 6 and cyclin D (Serrano et al., 1993). The lack of this complex formation maintains the retinoblastoma protein (Rb) in its hypo-phosphorylated and growth-suppressive states. This leads to the induction of G1 phase cell cycle arrest through the formation of the Rb/E2Fs-repressive complex (Fig. 1) (Weinberg, 1995). The loss of p16INK4a is increasingly common with advancing stages of various neoplasms, suggesting that p16INK4a inactivation may contribute to cancer progression. The frequent inactivation of p16INK4a induced by homozygous deletion or promoter hyper-methylation and point mutation has been observed in various cancers (Table 1).