Yale University

About: Yale University is a education organization based out in New Haven, Connecticut, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 89824 authors who have published 220665 publications receiving 12834776 citations. The organization is also known as: Yale & Collegiate School.

Disruption of IRS-2 causes type 2 diabetes in mice

Abstract: Human type 2 diabetes is characterized by defects in both insulin action and insulin secretion. It has been difficult to identify a single molecular abnormality underlying these features. Insulin-receptor substrates (IRS proteins) may be involved in type 2 diabetes: they mediate pleiotropic signals initiated by receptors for insulin and other cytokines1. Disruption of IRS-1 in mice retards growth, but diabetes does not develop because insulin secretion increases to compensate for the mild resistance to insulin2,3. Here we show that disruption of IRS-2 impairs both peripheral insulin signalling and pancreatic β-cell function. IRS-2-deficient mice show progressive deterioration of glucose homeostasis because of insulin resistance in the liver and skeletal muscle and a lack of β-cell compensation for this insulin resistance. Our results indicate that dysfunction of IRS-2 may contribute to the pathophysiology of human type 2 diabetes.

Firms in International Trade

Abstract: Despite the fact that importing and exporting are extremely rare firm activities, economists generally devote little attention to the role of firms when discussing international trade. This paper summarizes key differences between trading and non-trading firms, demonstrates how these differences present a challenge to standard trade models and shows how recent "heterogeneous-firm" models of international trade address these challenges. We then make use of transaction-level U.S. trade data to introduce a number of new stylized facts about firms and trade. These facts reveal that the extensive margins of trade -- that is, the number of products firms trade as well as the number of countries with which they trade -- are central to understanding the well-known role of distance in dampening aggregate trade flows.

Effects of Soft Drink Consumption on Nutrition and Health: A Systematic Review and Meta-Analysis

Abstract: In a meta-analysis of 88 studies, we examined the association between soft drink consumption and nutrition and health outcomes. We found clear associations of soft drink intake with increased energy intake and body weight. Soft drink intake also was associated with lower intakes of milk, calcium, and other nutrients and with an increased risk of several medical problems (e.g., diabetes).Study design significantly influenced results: larger effect sizes were observed in studies with stronger methods (longitudinal and experimental vs cross-sectional studies). Several other factors also moderated effect sizes (e.g., gender, age, beverage type). Finally, studies funded by the food industry reported significantly smaller effects than did non–industry-funded studies. Recommendations to reduce population soft drink consumption are strongly supported by the available science.

Requirement of JNK for Stress- Induced Activation of the Cytochrome c-Mediated Death Pathway

Abstract: The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to ultraviolet (UV) radiation. However, the functional consequence of JNK activation in UV-irradiated cells has not been established. It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts. Fibroblasts with simultaneous targeted disruptions of all the functional Jnk genes were protected against UV-stimulated apoptosis. The absence of JNK caused a defect in the mitochondrial death signaling pathway, including the failure to release cytochrome c. These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.

Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling

Abstract: Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2. The TSC1 and TSC2 gene products form a functional complex and inhibit phosphorylation of S6K and 4EBP1. These functions of TSC1/TSC2 are likely mediated by mTOR. Here we report that TSC2 is a GTPase-activating protein (GAP) toward Rheb, a Ras family GTPase. Rheb stimulates phosphorylation of S6K and 4EBP1. This function of Rheb is blocked by rapamycin and dominant-negative mTOR. Rheb stimulates the phosphorylation of mTOR and plays an essential role in regulation of S6K and 4EBP1 in response to nutrients and cellular energy status. Our data demonstrate that Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth.