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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.


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.


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.


Oyewumi M.O.,Northeastern Ohio Universities | Kumar A.,University of Texas at Austin | Cui Z.,University of Texas at Austin
Expert Review of Vaccines | Year: 2010

The development of novel immune adjuvants is emerging as a significant area of vaccine delivery based on the continued necessity to amplify immune responses to a wide array of new antigens that are poorly immunogenic. This article specifically focuses on the application of nanoparticles and microparticles as vaccine adjuvants. Many investigators are in agreement that the size of the particles is crucial to their adjuvant activities. However, reports on correlating the size of particle-based adjuvants and the resultant immune responses have been conflicting, with investigators on both sides of the fence with impressive data in support of the effectiveness of particles with small sizes (submicron) over those with larger sizes (micron) and vice versa, while other investigators reported data that showed submicron-and micron-sized particles are effective to the same degree as immune adjuvants. We have generated a list of biological, immunological and, more importantly, vaccine formulation parameters that may have contributed to the inconsistency from different studies and made recommendations on future studies attempting to correlate the size of particulate adjuvants and the immune responses induced. The information gathered could lead to strategies to optimize the performance of nano-microparticles as immune adjuvants. © 2010 Expert Reviews Ltd.


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.


Borges N.J.,Wright State University | Hartung P.J.,Northeastern Ohio Universities
Medical Teacher | Year: 2010

Background: Medical students' values represent an understudied area of research in medical education research. No known studies have investigated how medical students' values change over time from matriculation to graduation. Aim: Values are thought to remain relatively stable over the life course. However, little research supports this claim. Therefore, we examined the extent to which values change or remain the same during medical school. Method: Forty-six first-year medical students completed the Physician Values in Practice Scale (PVIPS) during their first and fourth years of medical school. The PVIPS contains 38 statements of values about medical practice and comprises six scales: Prestige, Service, Autonomy, Lifestyle, Management, and Scholarly Pursuits. Results: Matched pair t-tests (p < 0.05) indicated significant differences between students' PVIPS scores pretest (first year of medical school) and posttest (fourth year of medical school) for 2 of the 6 values (Autonomy: t(45)-4.12, p < 0.001 and Lifestyle: t(45)-2.62, p 0.012). Conclusions: Medical students values appear to change slightly during their 4 years of medical education. In line with literature suggesting that the medical education process is associated with change in certain student qualities and attributes (e.g., empathy), physician values may be another variable so affected. © 2010 Informa UK Ltd All rights reserved.


Longenecker R.J.,Northeastern Ohio Universities | Galazyuk A.V.,Northeastern Ohio Universities
JARO - Journal of the Association for Research in Otolaryngology | Year: 2011

Tinnitus, the perception of a sound without an external acoustic source, is a complex perceptual phenomenon affecting the quality of life in 17% of the adult population. Despite its ubiquity and morbidity, the pathophysiology of tinnitus is a work in progress, and there is no generally accepted cure or treatment. Development of a reliable common animal model is crucial for tinnitus research and may advance this field. The goal of this study was to develop a tinnitus mouse model. Tinnitus was induced in an experimental group of mice by an exposure to a loud (116 dB sound pressure level (SPL)) narrow band noise (one octave, centered at 16 kHz) during 1 h under anesthesia. The tinnitus was then assessed behaviorally by measuring gap induced suppression of the acoustic startle reflex. We found that a vast majority of the sound-exposed mice (86%) developed behavioral signs of tinnitus. This was a complex, long lasting, and dynamic process. On the day following exposure, all mice demonstrated signs of acute tinnitus over the entire range of sound frequencies used for testing (10-31 kHz). However, 2-3 months later, a behavioral evidence of tinnitus was evident only at a narrow frequency range (20-31 kHz) representing a presumed chronic condition. Extracellular recordings confirmed a significantly higher rate of spontaneous activity in inferior colliculus neurons in sound-exposed compared to control mice. Surprisingly, unilateral sound exposure suppresses startle responses in mice and they remained suppressed even 3 months post-exposure, whereas auditory brainstem response thresholds were completely recovered during 2 months following exposure. In summary, behavioral evidence of tinnitus can be reliably developed in mice by sound exposure, and tinnitus induction can be assessed by quantifying prepulse inhibition of the acoustic startle reflex. © 2011 Association for Research in Otolaryngology.


Song K.-H.,Northeastern Ohio Universities | Li T.,Northeastern Ohio Universities | Owsley E.,Northeastern Ohio Universities | Chiang J.Y.L.,Northeastern Ohio Universities
Journal of Lipid Research | Year: 2010

Cholesterol 7α-hydroxylase (CYP7A1) plays a critical role in regulation of bile acid synthesis in the liver. CYP7A1 mRNAs have very short half-lives, and bile acids destabilize CYP7A1 mRNA via the 3′-untranslated region (3′-UTR). However, the underlying mechanism of translational regulation of CYP7A1 mRNA remains unknown. Screening of a human micro RNA (miRNA) microarray has identified five differentially expressed miRNAs in human primary hepatocytes treated with chenodeoxycholic acid, GW4064, or fibroblast growth factor ( FGF)19. These compounds also significantly induced the expression of miR-122a, a liver-specific and the predominant miRNA in human hepatocytes. The putative recognition sequences for miR-122a and miR-422a were localized in the 3′-UTR of human CYP7A1 mRNA. The miR-122a and miR-422a mimics inhibited, whereas their inhibitors stimulated CYP7A1 mRNA expression. These miRNAs specifically inhibited the activity of the CYP7A1-3′-UTR reporter plasmids, and mutations of miRNA binding sites in 3′-UTR abrogated miRNA inhibition of reporter activity. These results suggest that miR-122a and miR-422a may destabilize CYP7A1 mRNA to inhibit CYP7A1 expression. However, these miRNAs did not play a role in mediating FGF19 inhibition of CYP7A1 transcription.jlr Under certain conditions, miRNA may reduce CYP7A1 mRNA stability to inhibit bile acid synthesis, and the miR-122a antagomirs may stimulate bile acid synthesis to reduce serum cholesterol and triglycerides. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc.


Thewissen J.G.M.,Northeastern Ohio Universities | Sensor J.D.,Northeastern Ohio Universities | Clementz M.T.,University of Wyoming | Bajpai S.,Indian Institute of Technology Roorkee
Paleobiology | Year: 2011

Dental morphology changes dramatically across the artiodactyl-cetacean transition, and it is generally assumed that this reflects the evolutionary change from herbivory and omnivory to carnivory. To test hypotheses regarding tooth function and diet, we studied size and position of wear facets on the lower molars and the stable isotopes of enamel samples. We found that nearly all investigated Eocene cetaceans had dental wear different from typical wear in ungulates and isotope values indicating that they hunted similar prey and processed it similarly. The only exception is the protocetid Babiacetus, which probably ate larger prey with harder skeletons. The closest relative of cetaceans, the raoellid artiodactyl Indohyus, had wear facets that resemble those of Eocene cetaceans more than they do facets of basal artiodactyls. This is in spite of Indohyus's tooth crown morphology, which is unlike that of cetaceans, and its herbivorous diet, as indicated by stable isotopes. This implies that the evolution of masticatory function preceded that of crown morphology and diet at the origin of cetaceans. © 2011 The Paleontological Society. All rights reserved.


Patel N.V.,Northeastern Ohio Universities | Pedersen J.C.,Northeastern Ohio Universities
Journal of Reconstructive Microsurgery | Year: 2012

In an attempt to decrease donor-site morbidity for rectus abdominis muscle harvest during free tissue transfer, we developed a technique of minimally invasive harvest. The da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA) was used in two cadavers for dissection and harvest of four rectus abdominis muscles. After the cadaver dissections were performed, the technique was used in a 30-year-old woman to harvest the left rectus abdominis muscle for free tissue transfer to a lower extremity defect. Four cadaver dissections for harvest of the rectus abdominis muscle using the da Vinci Surgical System were performed. In the cadavers and actual case, three ports (11 mm, 11 mm, and 15 mm) were used to access the abdominal cavity and perform the dissection. An additional 3 cm incision was used to remove the muscle from the abdominal cavity. The patient has not developed any surgical-site morbidity, including bulge or hernia in the 6 months postprocedure. Minimally invasive harvest of the rectus abdominis muscle is possible with the assistance of the da Vinci Surgical System. Potential benefits may include decreased surgical-site morbidity. Also, this may provide an approach to minimally invasive transperitoneal reconstruction. Copyright © 2012 by Thieme Medical Publishers, Inc.

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