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Mallick R.,Northeastern Ohio Universities | Patnaik S.,Roswell Park Cancer Institute | Yendamuri S.,State University of New York at Buffalo
Journal of Carcinogenesis | Year: 2010

MicroRNAs are tiny non-coding RNA molecules which play important roles in the epigenetic control of cellular processes by preventing the translation of proteins from messenger RNAs (mRNAs). A single microRNA can target different mRNAs, and an mRNA can be targeted by multiple microRNAs. Such complex interplays underlie many molecular pathways in cells, and specific roles for many microRNAs in physiological as well as pathological phenomena have been identified. Changes in expression of microRNAs have been associated with a wide variety of disease conditions, and microRNA-based biomarkers are being developed for the identification and monitoring of such states. This review provides a general overview of the current state of knowledge about the biology of microRNAs, and specific information about microRNAs with regard to the diagnosis and prognosis of lung cancer. © 2010 Mallick.

Chung S.,Seoul National University | Lee E.J.,Seoul National University | Yun S.,Seoul National University | Choe H.K.,Seoul National University | And 8 more authors.
Cell | Year: 2014

The circadian nature of mood and its dysfunction in affective disorders is well recognized, but the underlying molecular mechanisms are still unclear. Here, we show that the circadian nuclear receptor REV-ERBα, which is associated with bipolar disorder, impacts midbrain dopamine production and mood-related behavior in mice. Genetic deletion of the Rev-erbα gene or pharmacological inhibition of REV-ERBα activity in the ventral midbrain induced mania-like behavior in association with a central hyperdopaminergic state. Also, REV-ERBα repressed tyrosine hydroxylase (TH) gene transcription via competition with nuclear receptor-related 1 protein (NURR1), another nuclear receptor crucial for dopaminergic neuronal function, thereby driving circadian TH expression through a target-dependent antagonistic mechanism. In conclusion, we identified a molecular connection between the circadian timing system and mood regulation, suggesting that REV-ERBα could be targeting in the treatment of circadian rhythm-related affective disorders. © 2014 Elsevier Inc.

Recently, the Infectious Diseases Society published evidence-based guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The guideline discusses the management of a variety of infections including skin infections, bacteremia and endocarditis, pneumonia, and osteomyelitis and joint infections. Copyright © 2011 by Lippincott Williams & Wilkins.

Young J.W.,Northeastern Ohio Universities | Fleagle J.G.,State University of New York at Stony Brook
Biology Letters | Year: 2010

Studies of a diverse array of animals have found that young individuals often have robust bones for their body size (i.e. augmented crosssectional dimensions), limiting fracture risk despite general musculoskeletal immaturity. However, previous research has focused primarily on precocial taxa (e.g. rodents, lagomorphs, bovids, goats and emu). In this study, we examined the ontogenetic scaling of humeral and femoral cross-sectional robusticity in a mixedlongitudinal sample of two slow-growing, behaviourally altricial capuchin monkeys. Results showed that, when regressed against biomechanically appropriate size variables (i.e. the product of body mass and bone length), humeral and femoral bending strengths generally scale with negative allometry, matching the scaling patterns observed in previous studies of more precocial mammals. Additionally, bone strength relative to predicted loads (e.g. 'safety factors') peaks at birth and rapidly decreases during postnatal growth, falling to less than 5 per cent of peak values by weaning age. We suggest that increased safety factors during early ontogeny may be an adaptation to mitigate injury from falling during initial locomotor efforts. Overall, the results presented here suggest that ontogenetic declines in relative long bone strength may represent a common pattern among mammals that is perhaps preadaptive for different purposes among different lineages. © 2009 The Royal Society.

Partin J.F.,Akron General Medical Center | Partin J.F.,Northeastern Ohio Universities | Mamounas E.P.,Aultman Health Foundation | Mamounas E.P.,Northeastern Ohio Universities
Annals of Surgical Oncology | Year: 2011

Background: The development of multigene assays has proved useful in the clinical management of early-stage breast cancer. The 21-gene recurrence score (RS) assay has been shown to quantify risk of distant recurrence and predict chemotherapy benefit in node-negative and node-positive, estrogen-receptor (ER)-positive breast cancer patients. Small, single-institution series have shown that, compared with standard clinicopathologic criteria, use of RS significantly affects adjuvant chemotherapy recommendations. Methods: We performed a retrospective review of RS use and its effect on chemotherapy recommendations in nodenegative, ER-positive breast cancer patients at a tertiary care teaching hospital. Patient and tumor characteristics and adjuvant treatment information were obtained on 183 patients with RS results between January 2004 and October 2009. Risk categories were assigned based on the RS and on standard clinicopathologic criteria according to guidelines from NCCN, St. Gallen, and Adjuvant!. Results: A total of 14 patients were excluded for negative ER status (n = 2), insufficient data (n = 4), inclusion in TAILORx trial (n = 7), and recurrent breast cancer (n = 1), leaving 169 patients in the cohort. RS use increased 3-fold over the study period (from 18% in 2004 to 50% in 2009). Tumor grade, ER status, and PR status were significantly correlated with RS category. Overall concordance between RS and NCCN, St. Gallen, and Adjuvant! was 10, 48, and 50%, respectively. Depending on the guideline used for comparison, adjuvant therapy recommendations changed with the addition of the RS in 27-74% of cases. Conclusions: RS use is increasing, and the assay significantly reduced adjuvant chemotherapy utilization in nodenegative, ER-positive breast cancer patients. © Society of Surgical Oncology 2011.

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