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OBJECTIVE-To examine fat biopsy samples from lean insulinsensitive and obese insulin-resistant nondiabetic individuals for evidence of endoplasmic reticulum (ER) stress.RESEARCH DESIGN AND METHODS-Subcutaneous fat biopsies were obtained from the upper thighs of six lean and six obese nondiabetic subjects. Fat homogenates were used for proteomic (two-dimensional gel and MALDI-TOF/TOF), Western blot, and RT-PCR analysis.RESULTS-Proteomic analysis revealed 19 differentially upregulated proteins in fat of obese subjects. Three of these proteins were the ER stress-related unfolded protein response (UPR) proteins calreticulin, protein disulfide-isomerase A3, and glutathione-S-transferase P. Western blotting revealed upregulation of several other UPR stress-related proteins, including calnexin, a membrane-bound chaperone, and phospho c-jun NH 2 -terminal kinase (JNK)-1, a downstream effector protein of ER stress. RT-PCR analysis revealed upregulation of the spliced form of X-box binding protein-1s, a potent transcription factor and part of the proximal ER stress sensor inositol-requiring enzyme-1 pathway.CONCLUSIONS-These findings represent the first demonstration of UPR activation in subcutaneous adipose tissue of obese human subjects. As JNK can inhibit insulin action and activate proinflammatory pathways, ER stress activation of JNK may be a link between obesity, insulin resistance, and inflammation. Diabetes 57: [2438][2439][2440][2441][2442][2443][2444] 2008 O besity is associated with insulin resistance and with a low-grade state of inflammation (1). Whereas the cause of neither is completely understood, there is good evidence to show that free fatty acids (FFAs) play an important role in the development of obesity-related insulin resistance and inflammation (2). Plasma FFA levels are increased in most obese people (3). Acutely raising plasma FFA levels increases insulin resistance (4), whereas lowering plasma FFA levels reduces insulin resistance (5). Mechanisms involved in FFAinduced insulin resistance include accumulation (in muscle and liver) of lipids and lipid intermediates, including diacylglycerol; activation of several protein kinase C isoforms; and reduction in tyrosine phosphorylation of insulin receptor substrate-1/2 (6 -8). FFAs also activate the proinflammatory nuclear factor B pathway (6,9), in part, via signaling through toll-like receptor-4 pathways (10). However, not all obese, insulin-resistant subjects have elevated plasma FFA levels. It is therefore likely that there are other causes for obesityrelated insulin resistance. One of these appears to be endoplasmic reticulum (ER) stress. Indeed, chronic excessive nutrient intake has been shown to cause ER stress in adipose tissue of ob/ob mice and mice fed high-fat diets (11-13).The ER is a major site for protein as well as for lipid and sterol synthesis (14,15). Ribosomes attached to the ER membranes release newly synthesized peptides into the ER lumen, where protein chaperones and foldases assist in the proper posttranslational modification a...

School enrollment has universally increased over the last 25 years in low-income countries. Enrolling in school, however, does not assure that children learn. A large share of children in low-income countries complete their primary education lacking even basic reading, writing, and arithmetic skills. Teacher quality is a key determinant of student learning, but not much is known about teacher quality in low-income countries. This paper discusses an ongoing research program intended to help fill this void. We use data collected through direct observations, unannounced visits, and tests from primary schools in seven sub-Saharan African countries to answer three questions: How much do teachers teach? What do teachers know? How well do teachers teach?