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West Scarborough, MAINE, United States

Prudovsky I.,Maine Medical Center Research Institute
Nucleus (Austin, Tex.) | Year: 2012

Cycling eukaryotic cells rapidly re-establish the nuclear envelope and internal architecture following mitosis. Studies with a specific anti-nucleosome antibody recently demonstrated that the surface ("epichromatin") of interphase and mitotic chromatin possesses a unique and conserved conformation, suggesting a role in postmitotic nuclear reformation. Here we present evidence showing that the anionic glycerophospholipid phosphatidylserine is specifically located in epichromatin throughout the cell cycle and is associated with nucleosome core histones. This suggests that chromatin bound phosphatidylserine may function as a nucleation site for the binding of ER and re-establishment of the nuclear envelope. Source

Motyl K.J.,Maine Medical Center Research Institute
Discovery medicine | Year: 2011

Caloric restriction is associated with a reduction in body weight and temperature, as well as a reduction in trabecular bone volume and paradoxically an increase in adipocytes within the bone marrow. The nature of these adipocytes is uncertain, although there is emerging evidence of a direct relationship between bone remodeling and brown adipocytes. For example, in heterotrophic ossification, brown adipocytes set up a hypoxic gradient that leads to vascular invasion, chondrocyte differentiation, and subsequent bone formation. Additionally, deletion of retinoblastoma protein in an osteosarcoma model leads to increased hibernoma (brown fat tumor). Brown adipose tissue (BAT) becomes senescent with age at a time when thermoregulation is altered, bone loss becomes apparent, and sympathetic activity increases. Interestingly, heart rate is an unexpected but good predictor of fracture risk in elderly individuals, pointing to a key role for the sympathetic nervous system in senile osteoporosis. Hence the possibility exists that BAT could play an indirect role in age-related bone loss. However, evidence of an indirect effect from thermogenic dysfunction on bone loss is currently limited. Here, we present current evidence for a relationship between brown adipose tissue and bone as well as provide novel insights into the effects of thermoregulation on bone mineral density. Source

Rosen C.J.,Maine Medical Center Research Institute | Taylor C.L.,U.S. National Institutes of Health
Nature Reviews Endocrinology | Year: 2013

Misconceptions about vitamin D continue to grow despite publications in the past few years that have attempted to clarify risk. We present our perspective, and offer several conclusions. Calcium and vitamin D supplementation can reduce fracture risk by ∼10%. On the other hand, little evidence exists to support a threshold measure for vitamin D status (serum levels of 25-hydroxyvitamin D) above which fractures are reduced. The association of serum concentrations of 25-hydroxyvitamin D with other chronic diseases is confounded by multiple factors and conflicting outcomes that cannot be used to support a causal association. High doses of vitamin D supplements might not be completely harmless and should be avoided until additional data becomes available. Similarly, scant rationale exists for aggressive vitamin D supplementation for pregnant or lactating women. Dispelling misconceptions about vitamin D will ultimately benefit health-care providers and patients alike. © 2013 Macmillan Publishers Limited. All rights reserved. Source

Rosen C.J.,Maine Medical Center Research Institute
New England Journal of Medicine | Year: 2011

A healthy 61-year-old white woman is concerned about a low vitamin D level detected during an assessment of her skeletal health. Her menopause began at 54 years of age. She has no history of falls, and there is no family history of hip fracture. She takes no medications or supplements. Her height is 157.5 cm (5 ft 2 in.), and her weight 59.1 kg (130 lb). The results of a physical examination are unremarkable, and the findings on laboratory studies are normal. The T score for bone mineral density at the hip is -1.5, and the serum level of 25-hydroxyvitamin D is 21 ng per milliliter (53 nmol per liter). What do you advise? Copyright © 2011 Massachusetts Medical Society. Source

Scheller E.L.,University of Michigan | Rosen C.J.,Maine Medical Center Research Institute
Annals of the New York Academy of Sciences | Year: 2014

Marrow adipose tissue (MAT) is functionally distinct from both white and brown adipose tissue and can contribute to systemic and skeletal metabolism. MAT formation is a spatially and temporally defined developmental event, suggesting that MAT is an organ that serves important functions and, like other organs, can undergo pathologic change. The well-documented inverse relationship between MAT and bone mineral density has been interpreted to mean that MAT removal is a possible therapeutic target for osteoporosis. However, the bone and metabolic phenotypes of patients with lipodystrophy argues that retention of MAT may actually be beneficial in some circumstances. Furthermore, MAT may exist in two forms, regulated and constitutive, with divergent responses to hematopoietic and nutritional demands. In this review, we discuss the role of MAT in lipodystrophy, bone loss, and metabolism, and highlight our current understanding of this unique adipose tissue depot. © 2014 New York Academy of Sciences. Source

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