The role of estrogen receptor α in the regulation of bone and growth plate cartilage

Estrogens are important endocrine regulators of skeletal growth and maintenance in both females and males. Studies have demonstrated that the estrogen receptor (ER)-α is the main mediator of these estrogenic effects in bone. Therefore, estrogen signaling via ERα is a target both for affecting longitudinal bone growth and bone remodeling. However, treatment with estradiol (E2) leads to an increased risk of side effects such as venous thromboembolism and breast cancer. Thus, an improved understanding of the signaling pathways of ERα will be essential in order to find better bone specific treatments with minimal adverse effects for different estrogen-related bone disorders. This review summarizes the recent data regarding the intracellular signaling mechanisms, in vivo, mediated by the ERα activation functions (AFs), AF-1 and AF-2, and the effect on bone, growth plate and other estrogen responsive tissues. In addition, we review the recent cell-specific ERα-deleted mouse models lacking ERα specifically in neuronal cells or growth plate cartilage. The newly characterized signaling pathways of estrogen, described in this review, provide a better understanding of the ERα signaling pathways, which may facilitate the design of new, bone-specific treatment strategies with minimal adverse effects.     

Forecasting Hourly Peak Call Volume for a Rural Electric Cooperative Call Center

This research forecasts peak call volume of a centralized after‐hours call center for rural electric cooperatives to help the call center determine staffing levels. A Gaussian copula is used to capture the dependence among non‐normal distributions. Using a centralized call center reduces costs by approximately 75% compared to having individual call centers at each cooperative. Adding cooperatives to the centralized call center is projected to further decrease costs per member. An out‐of‐sample forecasting exercise after the call center expanded validated the model's forecast that additional cooperatives could be added without a proportional increase in the peak number of calls. Copyright © 2011 John Wiley & Sons, Ltd.     

药物发现的先驱者格特鲁德B·埃利昂(1918～1999)

G·B·埃利昂（CertrudeBelleElion）是本世纪获得诺贝尔生理学与医学奖仅有6位女性中的一位。尽管这位合理药物设计的先驱完全应该为自己所取得的成就感到骄傲,但她一点不关心这类华丽词藻和周围气氛。她真正关心的是她认为会对疾病本身产生最有效治疗的最好技术。从她1983年退休到1999年2月21日81岁时突然去世为止,实际上她从未停止过工作,有不少人已认识到,她只是表面上退休而已。G·B·埃利昂1918年出生于纽约,她的父母来自立陶宛和俄罗斯。在10岁时她的祖父和母亲死于癌症,这是她记忆中印象最深刻的事件。1937年她从亨特女子…     

Sex-dependence in triglyceride metabolism in response to dietary carbohydrates.

In humans, as well as in mice, fed on high carbohydrate diets, there was a significant sex difference in the plasma tirglycerides in that males had higher levels than females. This was mainly due to the difference in their removal rate of circulating triglycerides in the animals of both sexes. In mice, males had higher levels of liver triglycerides as well as higher rate of incorporation of U- 14C-glucose into liver triglycerides when compared to females.     

Somatostatin content and release of isolated pancreatic islets from obese-hyperglycemic mice.

The somatostatin content in pancreatic islets of obese-hyperglycemic mice was much lower than in the islets of normal mice. Also the release of somatostatin was decreased from the islets obtained from the obese-hyperglycemic mice. Tissue culture for 1 week changed neither the content of, nor the amount of somatostatin released from, the pancreatic islets.     

Complexed rheumatoid factor measurements in sera, synovial fluids and in immune complex fractions.

Mild acidic treatment increases the rheumatoid factor titre of some sera and synovial fluids (SF) in rheumatoid arthritis (RA), juvenile RA (JRA) and most frequently in rheumatoid vasculitis. This unmasking of 'hidden' RF in serum and SF samples correlated with the RF-immune complexes (RF-IC) and complexed C4 present in the 3% polyethylene glycol (PEG) precipitates, indicating that by means of 'hidden' RF measurements RF-ICs are possibly detected. This method seems to provide a diagnostic tool for detecting RF-ICs in RA and other related diseases.     

Changes in beta-2 adrenergic receptor sensitivity with maturation of erythroid progenitor cells.

Erythroid burst forming units (BFU-E) were much more sensitive to the beta-2 selective adrenergic drug, salbutamol, than erythroid colony forming units (CFU-E) in an in vitro study of erythroid progenitor cells.