Maternal low-protein diet (LP) throughout gestation affects pancreatic β-cell fraction of the offspring at birth, thus increasing their susceptibility to type 2 diabetes in adulthood. The present study sought to strictly examine the effects of LP during the last week of gestation (LP12.5) as a developmental window for β-cell programming and metabolic dysfunction in adulthood. Islet morphology analysis revealed normal β-cell fraction in LP12.5 newborns. Normal glucose tolerance was observed in 6-8 weeks old male and female LP12.5 offspring. However, male LP12.5 offspring displayed glucose intolerance and reduced insulin sensitivity associated with β-cell dysfunction with aging. High-fat diet exposure of metabolically normal 12-week-old male LP12.5 induced glucose intolerance due to increased body weight, insulin resistance and insufficient β-cell mass adaptation despite higher insulin secretion. Assessment of epigenetic mechanisms through MicroRNAs (miRs) by a real-time PCR-based microarray in islets revealed elevation in miRs that regulate insulin secretion (miRs 342, 143), insulin resistance (miR 143), and obesity (miR 219). In the islets, overexpression of miR 143 reduced insulin secretion in response to glucose. In contrast to the model of LP exposure throughout pregnancy, islet protein levels of mTOR and Pdx1 were normal in LP12.5 islets. Collectively, these data suggest that LP diet during the last week of pregnancy is critical and sufficient to induce specific and distinct developmental programming effects of tissues that control glucose homeostasis, causing permanent changes in specific set of microRNAs that may contribute to the overall vulnerability of the offspring to obesity, insulin resistance and type 2 diabetes.

Multinational Enterprises (MNEs) periodically decide on both which products to launch (or phase out) and in which global regions, thereby conducting an integrated products-countries consideration in diversification strategies. Over time, these diversification decisions can have a cumulative impact on the structure. Diversification literature has primarily focused on one of these two metrics rather than providing an integrated view; this work investigates both metrics. Considering deal-making as an execution instrument of strategies, a comparison of historic deals of MNEs with their current structure offers insights into the nature of the diversification strategies that were pursued. For the most active global deal-making pharmaceutical firms, we derive normalized deal diversity profile metrics in terms of their cumulative past product-countries’ preferences and compare them with the product-countries’ operations of their current subsidiaries. We rationalize MNE deal behaviors as means to shed, acquire and consolidate businesses to enable their market leadership aspirations. The analysis reveals two trajectories that have been actively favored in deals: one directed at niche products offered globally, and one directed at niche products in selected countries. The former is characterized by deals in a high number of countries, whereas the latter by two identifiably different product concentration levels. In contrast, trajectories directed at widely diverse products have been disfavored in deals. Understanding such directions and their pace can aid in global- or group-level strategy formulation, monitoring strategy execution, interpreting competitor moves and designing regional policies.