338 research outputs found

    Technology in University Physical Activity Courses: A Mini-Ethnographic Case Study

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    As younger generations become increasingly reliant on technology, higher educational institutions must continually attempt to stay with or ahead of the curve to foster 21st century teaching and learning. College and university physical activity courses (PACs) are encouraged to incorporate technology for effective pedagogical practices. No qualitative research has specifically examined the culture of PACs instructors’ attitudes and experiences with technology as a pedagogical tool. A mini-ethnographic case study explored the use of technology among seven graduate teaching assistants who shared their pedagogical experiences, teaching practices, and perceptions of technology within PACs. Using an interpretive phenomenological analysis, composite narrative accounts were presented to highlight unique characteristics of PAC instructors and develop meaning from their lived experiences. The findings revealed that PAC instructors use varying forms of technology, but all instructors rely on learning management systems as a pedagogical tool, which can be influenced by campus environment, pedagogical experiences, and social support. This pilot study contributes to the current gap in research related to technology in PACs and addresses the need to properly prepare instructors to teach in the digital age

    MAPping the Chiral Inversion and Structural Transformation of a Metal-Tripeptide Complex having Ni-SOD Activity

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Inorganic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ic102295s.The metal abstraction peptide (MAP) tag is a tripeptide sequence capable of abstracting a metal ion from a chelator and binding it with extremely high affinity at neutral pH. Initial studies on the nickel-bound form of the complex demonstrate that the tripeptide asparagine-cysteine-cysteine (NCC) binds metal with 2N:2S, square planar geometry and behaves as both a structural and functional mimic of Ni superoxide dismutase (Ni-SOD). Electronic absorption, circular dichroism (CD), and magnetic CD (MCD) data collected for Ni-NCC are consistent with a diamagnetic NiII center. It is apparent from the CD signal of Ni-NCC that the optical activity of the complex changes over time. Mass spectrometry data show that the mass of the complex is unchanged. Combined with the CD data, this suggests that chiral rearrangement of the complex occurs. Following incubation of the nickel-containing peptide in D2O and back-exchange into H2O, incorporation of deuterium into non-exchangeable positions is observed, indicating chiral inversion occurs at two of the alpha carbon atoms in the peptide. Control peptides were used to further characterize the chirality of the final nickel-peptide complex, and DFT calculations were performed to validate the hypothesized position of the chiral inversions. In total, these data indicate Ni-SOD activity is increased proportionally to the degree of structural change in the complex over time, as cross-correlation between the change in CD signal and change in SOD activity reveals a linear relationship

    Controlling the Chiral Inversion Reaction of the Metallopeptide Ni-Asparagine-Cysteine-Cysteine with Dioxygen

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Inorganic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ic301717q.Synthetically generated metallopeptides have the potential to serve a variety of roles in biotechnology applications, but the use of such systems is often hampered by the inability to control secondary reactions. We have previously reported that the NiII complex of the tripeptide LLL-asparagine-cysteine-cysteine, LLL-NiII-NCC, undergoes metal-facilitated chiral inversion to DLD-NiII-NCC, which increases the observed superoxide scavenging activity. However, the mechanism for this process remained unexplored. Electronic absorption and circular dichroism studies of the chiral inversion reaction of NiII-NCC reveal a unique dependence on dioxygen. Specifically, in the absence of dioxygen, the chiral inversion is not observed, even at elevated pH, whereas the addition of O2 initiates this reactivity and concomitantly generates superoxide. Scavenging experiments using acetaldehyde are indicative of the formation of carbanion intermediates, demonstrating that inversion takes place by deprotonation of the alpha carbons of Asn1 and Cys3. Together, these data are consistent with the chiral inversion being dependent on the formation of a NiIII-NCC intermediate from NiII-NCC and O2. The data further suggest that the anionic thiolate and amide ligands in NiII-NCC inhibit Cα–H deprotonation for the NiII oxidation state, leading to a stable complex in the absence of O2. Together, these results offer insights into the factors controlling reactivity in synthetic metallopeptides

    A novel tripeptide model of nickel superoxide dismutase

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Inorganic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ic901828m.Nickel superoxide dismutase (Ni-SOD) catalyzes the disproportionation of superoxide to molecular oxygen and hydrogen peroxide, but the overall reaction mechanism has yet to be determined. Peptide-based models of the 2N:2S nickel coordination sphere of Ni-SOD have provided some insight into the mechanism of this enzyme. Here we show that the coordination sphere of Ni-SOD can be mimicked using the tripeptide asparagine-cysteine-cysteine (NCC). NCC binds nickel with extremely high affinity at physiological pH with 2N:2S geometry, as demonstrated by electronic absorption and circular dichroism (CD) data. Like Ni-SOD, Ni-NCC has mixed amine/amide ligation that favors metal-based oxidation over ligand-based oxidation. Electronic absorption, CD, and magnetic CD data (MCD) collected for Ni-NCC are consistent with a diamagnetic Ni(II) center bound in square planar geometry. Ni-NCC is quasi-reversibly oxidized with a midpoint potential of 0.72(2) V (versus Ag/AgCl) and breaks down superoxide in an enzyme-based assay, supporting its potential use as a model for Ni-SOD chemistry

    Left ventricular diastolic dysfunction in Nrf2 knock out mice is associated with cardiac hypertrophy, decreased expression of SERCA2a, and preserved endothelial function

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    AbstractIncreased production of reactive oxygen species and failure of the antioxidant defense system are considered to play a central role in the pathogenesis of cardiovascular disease. The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key master switch controlling the expression of antioxidant and protective enzymes, and was proposed to participate in protection of vascular and cardiac function. This study was undertaken to analyze cardiac and vascular phenotype of mice lacking Nrf2. We found that Nrf2 knock out (Nrf2 KO) mice have a left ventricular (LV) diastolic dysfunction, characterized by prolonged E wave deceleration time, relaxation time and total diastolic time, increased E/A ratio and myocardial performance index, as assessed by echocardiography. LV dysfunction in Nrf2 KO mice was associated with cardiac hypertrophy, and a downregulation of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) in the myocardium. Accordingly, cardiac relaxation was impaired, as demonstrated by decreased responses to β-adrenergic stimulation by isoproterenol ex vivo, and to the cardiac glycoside ouabain in vivo. Surprisingly, we found that vascular endothelial function and endothelial nitric oxide synthase (eNOS)-mediated vascular responses were fully preserved, blood pressure was decreased, and eNOS was upregulated in the aorta and the heart of Nrf2 KO mice. Taken together, these results show that LV dysfunction in Nrf2 KO mice is mainly associated with cardiac hypertrophy and downregulation of SERCA2a, and is independent from changes in coronary vascular function or systemic hemodynamics, which are preserved by a compensatory upregulation of eNOS. These data provide new insights into how Nrf2 expression/function impacts the cardiovascular system

    Mosque-based emotional support among young Muslim Americans

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    Despite a growing literature on social support networks in religious settings (i.e., church-based social support), little is known about mosque-based support among Muslims. This study investigates the demographic and religious behavior correlates of mosque-based social support among a multi-racial and ethnic sample of 231 young Muslims from southeast Michigan. Several dimensions of mosque-based support are examined including receiving emotional support, giving emotional support, anticipated emotional support and negative interactions with members of one’s mosque. Results indicated that women both received and antic- ipated receiving greater support than did men. Higher educational attainment was associated with receiving and giving less support compared to those with the lowest level of educational attainment. Moreover, highly educated members reported fewer negative interactions than less educated members. Mosque attendance and level of congregational involvement positively predicted receiving, giving, and anticipated emotional support from congregants, but was unrelated to negative interactions. Overall, the study results converge with previously established correlates of church- based emotional support.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107410/1/art%3A10.1007%2Fs13644-013-0119-0(1).pd

    Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

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    Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research

    Embedding the Ni-SOD mimetic Ni-NCC within a polypeptide sequence alters specificity of the reaction pathway

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Inorganic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ic301175f.The unique metal abstracting peptide (MAP) asparagine-cysteine-cysteine (NCC) binds nickel in a square planar 2N:2S geometry and acts as a mimic of the enzyme nickel superoxide dismutase (Ni-SOD). The Ni-NCC tripeptide complex undergoes rapid, site-specific chiral inversion to DLD-NCC in the presence of oxygen. Superoxide scavenging activity increases proportionally with the degree of chiral inversion. Characterization of the NCC sequence within longer peptides with absorption, circular dichroism (CD), and magnetic CD (MCD) spectroscopies and mass spectrometry (MS) shows that the geometry of metal coordination is maintained, though the electronic properties of the complex are varied to a small extent due to bis-amide, rather than amine/amide, coordination. In addition, both the Ni-tripeptides and Ni-pentapeptides have a −2 charge. The study here demonstrates that the chiral inversion chemistry does not occur when NCC is embedded in a longer polypeptide sequence. Nonetheless, the superoxide scavenging reactivity of the embedded Ni-NCC module is similar to that of the chirally inverted tripeptide complex, which is consistent with a minor change in reduction potential for the Ni-pentapeptide. Together, this suggests that the charge of the complex could affect the SOD activity as much as a change in primary coordination sphere. In Ni-NCC and other Ni-SOD mimics, changes in chirality, superoxide scavenging activity, and oxidation of the peptide itself all depend on the presence of dioxygen or its reduced derivatives (e.g., superoxide), and the extent to which each of these distinct reactions occurs is ruled by electronic and steric effects that emenate from the organization of ligands around the metal center

    Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer

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    FEN1 has key roles in Okazaki fragment maturation during replication, long patch base excision repair, rescue of stalled replication forks, maintenance of telomere stability and apoptosis. FEN1 may be dysregulated in breast and ovarian cancers and have clinicopathological significance in patients. We comprehensively investigated FEN1 mRNA expression in multiple cohorts of breast cancer [training set (128), test set (249), external validation (1952)]. FEN1 protein expression was evaluated in 568 oestrogen receptor (ER) negative breast cancers, 894 ER positive breast cancers and 156 ovarian epithelial cancers. FEN1 mRNA overexpression was highly significantly associated with high grade (p= 4.89 x 10 - 57) , high mitotic index (p= 5.25 x 10 - 28), pleomorphism (p= 6.31 x 10-19), ER negative (p= 9.02 x 10-35 ), PR negative (p= 9.24 x 10-24 ), triple negative phenotype (p= 6.67 x 10-21) , PAM50.Her2 (p=5.19 x 10-13 ), PAM50.Basal (p=2.7 x 10-41), PAM50.LumB (p=1.56 x 10-26), integrative molecular cluster 1 (intClust.1) ( p=7.47 x 10-12), intClust.5 (p=4.05 x 10-12) and intClust. 10 (p=7.59 x 10-38 ) breast cancers. FEN1 mRNA overexpression is associated with poor breast cancer specific survival in univariate (p=4.4 x 10-16) and multivariate analysis (p=9.19 x 10-7). At the protein level, in ER positive tumours , FEN1 overexpression remains significantly linked to high grade, high mitotic index and pleomorphism (ps< 0.01). In ER negative tumours, high FEN1 is significantly associated with pleomorphism, tumour type, lymphovascular invasion, triple negative phenotype, EGFR and HER2 expression (ps<0.05). In ER positive as well as in ER negative tumours, FEN1 protein over expression is associated with poor survival in univariate and multivariate analysis (ps<0.01). In ovarian epithelial cancers , similarly, FEN1 overexpression is associated with high grade, high stage and poor survival (ps<0.05). We conclude that FEN1 is a promising biomarker in breast and ovarian epithelial cancer
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