Elementary school classroom physical activity breaks: student, teacher, and facilitator perspectives.

Current physical activity (PA) guidelines recommend that children accumulate at least 60 min of PA each day, and that adults should collaborate across sectors to increase opportunities for PA. Implementing brief classroom PA breaks (CPABs) is one way to help increase daily PA. The primary purpose of this study was to determine perceptions of a 14-wk CPAB program among elementary school children, in the first through fourth grades ( n = 254), at a suburban elementary school, and their teachers ( n = 18). The CPAB program was implemented by university exercise science students, and student and teacher perceptions were assessed through surveys. The children reported that the CPABs were very fun (86%), provided them with a nice break during the school day (88%), were very good for their health (94%), helped them feel more ready to learn (71%), and learn better (50%). The teachers reported that the students really enjoyed the CPABs (100%), that encouraging students to be physically active was either very important (83%) or important (17%), and that they were either very confident (72%) or confident (28%) that they themselves could lead the CPABs. No teacher reported that the CPABs hindered classroom learning. CPABs appear to be enjoyable to both students and teachers, easy to administer, and supportive of learning. Recommendations for improvements within the present collaboration were minimal and could be easily addressed with firmer entrenchment of the program. This collaboration was beneficial and fun for the vast majority involved, and others are urged to implement similar programs.

Geminin overexpression promotes imatinib sensitive breast cancer: a novel treatment approach for aggressive breast cancers, including a subset of triple negative.

Breast cancer is the second leading cause of cancer-related deaths in women. Triple negative breast cancer (TNBC) is an aggressive subtype that affects 10-25% mostly African American women. TNBC has the poorest prognosis of all subtypes with rapid progression leading to mortality in younger patients. So far, there is no targeted treatment for TNBC. To that end, here we show that c-Abl is one of several tyrosine kinases that phosphorylate and activate geminin's ability to promote TNBC. Analysis of >800 breast tumor samples showed that geminin is overexpressed in ∼50% of all tumors. Although c-Abl is overexpressed in ∼90% of all tumors, it is only nuclear in geminin overexpressing tumors. In geminin-negative tumors, c-Abl is only cytoplasmic. Inhibiting c-Abl expression or activity (using imatinib or nilotinib) prevented geminin Y150 phosphorylation, inactivated the protein, and most importantly converted overexpressed geminin from an oncogene to an apoptosis inducer. In pre-clinical orthotopic breast tumor models, geminin-overexpressing cells developed aneuploid and invasive tumors, which were suppressed when c-Abl expression was blocked. Moreover, established geminin overexpressing orthotopic tumors regressed when treated with imatinib or nilotinib. Our studies support imatinib/nilotonib as a novel treatment option for patients with aggressive breast cancer (including a subset of TNBCs)-overexpressing geminin and nuclear c-Abl.

BRCA1/p220 loss triggers BRCA1-IRIS overexpression via mRNA stabilization in breast cancer cells.

BRCA1/p220-assocaited and triple negative/basal-like (TN/BL) tumors are aggressive and incurable breast cancer diseases that share among other features the no/low BRCA1/p220 expression. Here we show that BRCA1/p220 silencing in normal human mammary epithelial (HME) cells reduces expression of two RNA-destabilizing proteins, namely AUF1 and pCBP2, both proteins bind and destabilize BRCA1-IRIS mRNA. BRCA1-IRIS overexpression in HME cells triggers expression of several TN/BL markers, e.g., cytokeratins 5 and 17, p-cadherin, EGFR and cyclin E as well as expression and activation of the pro-survival proteins; AKT and survivin. BRCA1-IRIS silencing in the TN/BL cell line, SUM149 or restoration of BRCA1/p220 expression in the mutant cell line, HCC1937 reduced expression of TN/BL markers, AKT and survivin and induced cell death. Collectively, we propose that BRCA1/p220 loss of expression or function triggers BRCA1-IRIS overexpression through a post-transcriptional mechanism, which in turn promotes formation of aggressive and invasive breast tumors by inducing expression of TN/BL and survival proteins.

Physiological and Perceptual Responses to Nintendo® Wii Fit™ in Young and Older Adults.

Physically active video gaming (AVG) provides a technologically-modern, convenient means of increasing physical activity (PA). This study examined cardiovascular, metabolic, and perceptual responses in young adult (AP) and older adult (OP) participants engaging in Wii FitTM AVG play, and compared PA levels during play to recommended PA levels. Heart rate (HR), percent heart rate reserve (%HRR), oxygen consumption (VO2), energy expenditure (EE), rating of perceived exertion (RPE), enjoyment level (EL), and step count data were obtained from 10 YP and 10 OP during 15 minutes of rest and four 15-minute bouts of Wii FitTM activities (yoga, balance, aerobics, strength). For all participants, AVG significantly increased HR, VO2, and EE measures above rest, with significant between-activity differences. Responses were similar between YP and OP, except that the activities were more intense for OP, in terms of %HRR and RPE. Most games elicited responses consistent with light-intensity PA, though peak HR and VO2 values for aerobic and strength games met or approached recommended PA intensities. Wii FitTM appears to provide an enjoyable form of light PA for both YP and OP, which can reduce inactive screen time and provide beneficial cardiovascular, musculoskeletal, and metabolic stimulation.

Geminin overexpression induces mammary tumors via suppressing cytokinesis.

Aneuploidy plays an important role in the development of cancer. Here, we uncovered an oncogenic role for geminin in mitotic cells. In addition to chromatin, tyrosine phosphorylated geminin also localizes to centrosome, spindle, cleavage furrow and midbody during mitosis. Geminin binding to Aurora B prevents its binding to INCENP, and thus activation leading to lack of histone H3-(serine 10) phosphorylation, chromosome condensation failure, aborted cytokinesis and the formation of aneuploid, drug resistance cells. Geminin overexpressing human mammary epithelial cells form aneuploid, aggressive tumors in SCID mice. Geminin is overexpressed in more than half of all breast cancers analyzed. The current study reveals that geminin is a genuine oncogene that promotes cytokinesis failure and production of aneuploid, aggressive breast tumors when overexpressed and thus a worthy therapeutic target (oncotarget) for aggressive breast cancer.

Geminin overexpression prevents the completion of topoisomerase IIα chromosome decatenation, leading to aneuploidy in human mammary epithelial cells.

INTRODUCTION: The nuclear enzyme topoisomerase IIα (TopoIIα) is able to cleave DNA in a reversible manner, making it a valuable target for agents such as etoposide that trap the enzyme in a covalent bond with the 5' DNA end to which it cleaves. This prevents DNA religation and triggers cell death in cancer cells. However, development of resistance to these agents limits their therapeutic use. In this study, we examined the therapeutic targeting of geminin for improving the therapeutic potential of TopoIIα agents. METHODS: Human mammary epithelial (HME) cells and several breast cancer cell lines were used in this study. Geminin, TopoIIα and cell division cycle 7 (Cdc7) silencing were done using specific small interfering RNA. Transit or stable inducible overexpression of these proteins and casein kinase Iε (CKIε) were also used, as well as several pharmacological inhibitors that target TopoIIα, Cdc7 or CKIε. We manipulated HME cells that expressed H2B-GFP, or did not, to detect chromosome bridges. Immunoprecipitation and direct Western blot analysis were used to detect interactions between these proteins and their total expression, respectively, whereas interactions on chromosomal arms were detected using a trapped in agarose DNA immunostaining assay. TopoIIα phosphorylation by Cdc7 or CKIε was done using an in vitro kinase assay. The TopoGen decatenation kit was used to measure TopoIIα decatenation activity. Finally, a comet assay and metaphase chromosome spread were used to detect chromosome breakage and changes in chromosome condensation or numbers, respectively. RESULTS: We found that geminin and TopoIIα interact primarily in G2/M/early G1 cells on chromosomes, that geminin recruits TopoIIα to chromosomal decatenation sites or vice versa and that geminin silencing in HME cells triggers the formation of chromosome bridges by suppressing TopoIIα access to chromosomal arms. CKIε kinase phosphorylates and positively regulates TopoIIα chromosome localization and function. CKIε kinase overexpression or Cdc7 kinase silencing, which we show phosphorylates TopoIIα in vitro, restored DNA decatenation and chromosome segregation in geminin-silenced cells before triggering cell death. In vivo, at normal concentration, geminin recruits the deSUMOylating sentrin-specific proteases SENP1 and SENP2 enzymes to deSUMOylate chromosome-bound TopoIIα and promote its release from chromosomes following completion of DNA decatenation. In cells overexpressing geminin, premature departure of TopoIIα from chromosomes is thought to be due to the fact that geminin recruits more of these deSUMOylating enzymes, or recruits them earlier, to bound TopoIIα. This triggers premature release of TopoIIα from chromosomes, which we propose induces aneuploidy in HME cells, since chromosome breakage generated through this mechanism were not sensed and/or repaired and the cell cycle was not arrested. Expression of mitosis-inducing proteins such as cyclin A and cell division kinase 1 was also increased in these cells because of the overexpression of geminin. CONCLUSIONS: TopoIIα recruitment and its chromosome decatenation function require a normal level of geminin. Geminin silencing induces a cytokinetic checkpoint in which Cdc7 phosphorylates TopoIIα and inhibits its chromosomal recruitment and decatenation and/or segregation function. Geminin overexpression prematurely deSUMOylates TopoIIα, triggering its premature departure from chromosomes and leading to chromosomal abnormalities and the formation of aneuploid, drug-resistant cancer cells. On the basis of our findings, we propose that therapeutic targeting of geminin is essential for improving the therapeutic potential of TopoIIα agents.

Y chromosome STR allelic and haplotype diversity in five ethnic Tamil populations from Tamil Nadu, India.

We have analyzed 17 Y chromosomal STR loci in a population sample of 154 unrelated male individuals of the Tamil ethnic group residing in the state of Tamil Nadu, Southern India using AmpFlSTR(R) Yfiler PCR amplification kit. The population samples consist of the following castes: Kongu Gounder (KOG), Nadar Hindu (NAH), Agamudayar (AGA), Parayar (PAR) and other Tamil individuals (MCT) of mixed castes. A total of 152 unique haplotypes were identified among the 154 individuals studied. The haplotype diversity was found to be 0.9935 or higher for all the five groups. The results of population pairwise Fst p values indicate no statistically significant differentiation between the five populations in this study, but the results were highly significant when compared with 12 other global populations (p<0.05). Comparison of populations in this study with other national and global populations using Principal co-ordinate analysis (PCA) using Rst distance matrix indicates a delineation of all the Indian populations from other unrelated populations.

Effects of resistance training and protein supplementation on bone turnover in young adult women.

BACKGROUND: The strength of aging bone depends on the balance between the resorption and formation phases of the remodeling process. The purpose of this study was to examine the interaction of two factors with the potential to exert opposing influences on bone turnover, resistance exercise training and high dietary protein intake. It was hypothesized that resistance training by young, healthy, untrained women with protein intakes near recommended levels (0.8 g.kg(-1).d(-1)) would promote bone formation and/or inhibit bone resorption, and that subsequent supplementation to provide 2.4 g protein.kg(-1).d(-1) would reverse these effects. METHODS: Bone formation was assessed with serum bone-specific alkaline phosphatase (BAP) and osteocalcin (OC), and bone resorption with urinary calcium and deoxypyridinoline (DPD). Biochemical, strength, anthropometric, dietary, and physical activity data were obtained from 24 healthy, untrained, eumenorrheic women (18-29 y) at baseline, after eight weeks of resistance training (3 d.wk(-1), approximately 1 hr.d(-1); 3 sets, 6-10 repetitions, 13 exercises, 75-85% maximum voluntary contraction), and after 12 weeks of resistance training and 10 days of protein/placebo supplementation. Subjects were randomized (double-blind) to either a high protein (HP) or training control (TC) group and, during the final 10 days, consumed either enough purified whey protein to bring daily protein intake to 2.4 g.kg(-1).d(-1), or an equivalent dose of isoenergetic, carbohydrate placebo. RESULTS: Strength, lean tissue mass, and DPD increased significantly in both groups over time, while percent body fat and BAP decreased (repeated measures ANOVA, p < or = 0.05, Bonferroni correction). No significant changes were observed for serum OC or urinary calcium, and no significant group (TC, HP) x time (baseline, week 8, week 12) interactions emerged for any of the biochemical measures. CONCLUSION: (1) Twelve weeks of high-intensity resistance training did not appear to enhance bone formation or inhibit bone resorption in young adult women, as assessed by biochemical markers of bone metabolism. (2) Subsequent maintenance of a high protein intake for 10 days in these regularly-training, calcium-replete women also showed no effects on bone metabolism.

Effect of creatine loading on anaerobic performance and skeletal muscle volume in NCAA Division I athletes.

OBJECTIVE: We measured the effect of 3 d of creatine (Cr) supplementation on repeated sprint performance and thigh muscle volume in elite power athletes. METHODS: Ten male (mean +/- standard deviation of body mass and percentage of fat (81.1 +/- 10.5 kg and 9.8 +/- 3.5) and ten female (58.4 +/- 5.3 kg and 15.0 +/- 3.4) athletes were matched for sex and 10-s cycle sprint scores, paired by rank, and randomly assigned to the Cr or placebo (P) group. Subjects completed six maximal 10-s cycle sprints interspersed with 60 s of recovery before and after 3 d of Cr (0.35 g/kg of fat-free mass) or P (maltodextrin) ingestion. Before and after supplementation, 10 contiguous transaxial images of both thighs were obtained with magnetic resonance imaging. RESULTS: Cr supplementation resulted in statistically significant increases in body mass (0.9 +/- 0.1 kg, P < 0.03), total work during the first sprint (P < 0.04), and peak power during sprints 2 to 6 (P < 0.10). As expected, total work and peak power values for males were greater than those for their female counterparts during the initial sprint (P < 0.02); however, the reverse was true during the last three sprints (P < 0.01). Imaging data showed a 6.6% increase in thigh volume in five of six Cr subjects (P = 0.05). CONCLUSION: These data indicate that 3 d of Cr supplementation can increase thigh muscle volume and may enhance cycle sprint performance in elite power athletes; moreover, this effect is greater in females as sprints are repeated.