162 research outputs found

    Effects of Calcium Pyruvate Supplementation During Training On Body Composition, Exercise Capacity, and Metabolic Responses To Exercise

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    Objective: We evaluated the effects of calcium pyruvate supplementation during training on body composition and metabolic responses to exercise. Method: Twenty-three untrained females were matched and assigned to ingest in a double blind and randomized manner either 5 g of calcium pyruvate (PYR) or a placebo (PL) twice daily for 30 d while participating in a supervised exercise program. Prior to and following supplementation, subjects had body composition determined via hydrodensiometry; performed a maximal cardiopulmonary exercise test; and performed a 45-min walk test at 70% of pre-training VO2 max in which fasting pre- and post exercise blood samples determined. Results: No significant differences were observed between groups in energy intake or training volume. Univariate repeated measures ANOVA revealed that subjects in the PYR group gained less weight (PL 1.2 ± 0.3, PYR 0.3 ± 0.3 kg, P = 0.04), lost more fat (PL 1.1 ± 0.5; PYR −0.4 ± 0.5 kg, P = 0.03), and tended to lose a greater percentage of body fat (PL 1.0 ± 0.7; PYR −0.65 ± 0.6%, P = 0.07), with no differences observed in fat-free mass (PL 0.1 ± 0.5; PYR 0.7 ± 0.3 kg, P = 0.29). However, these changes were not significant when body composition data were analyzed by MANOVA (P = 0.16). There was some evidence that PYR may negate some of the beneficial effects of exercise on HDL values. No significant differences were observed between groups in maximal exercise responses or metabolic responses to submaximal walking. Conclusions: Results indicate that PYR supplementation during training does not significantly affect body composition or exercise performance and may negatively affect some blood lipid levels

    There is more to accommodation of the eye than simply minimizing retinal blur.

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    Eyes of children and young adults change their optical power to focus nearby objects at the retina. But does accommodation function by trial and error to minimize blur and maximize contrast as is generally accepted? Three experiments in monocular and monochromatic vision were performed under two conditions while aberrations were being corrected. In the first condition, feedback was available to the eye from both optical vergence and optical blur. In the second, feedback was only available from target blur. Accommodation was less precise for the second condition, suggesting that it is more than a trial-and-error function. Optical vergence itself seems to be an important cue for accommodation

    Creativity, play and transgression: children transforming spatial design

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    Spatial designers, who engage children in their design process, most often frame children in this context as experts in their own lives. Findings from a study based at the University of Sheffield, point to new understandings of this participatory role, in which children move towards the role of designer. Drawing on interviews including visual methods with 16 spatial designers and guided by phenemonography, the paper seeks to represent the designers’ perspectives on the under-explored area of child–designer interactions. Findings suggest that the designers understand these interactions to comprise a reciprocal and co-created space – a sphere of behaviours, actions and ways of being which together becomes an enabler of change. It is proposed that what Bhabha (The Location of Culture, 1994) refers to as a ‘Third Space’ in which the ‘dominant culture might be temporarily subverted and its structural systems of power and control renegotiated’ can be re-imagined in this co-design context. The paper weaves together theoretical discourse and empirical illustrations of perceived creativity, play and transgression, which – at their intersection – support a potential transformation of understandings of children as co-designers and of the design process itself

    The Chemopreventive Effects of Protandim: Modulation of p53 Mitochondrial Translocation and Apoptosis during Skin Carcinogenesis

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    Protandim, a well defined dietary combination of 5 well-established medicinal plants, is known to induce endogenous antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Our previous studies have shown through the induction of various antioxidant enzymes, products of oxidative damage can be decreased. In addition, we have shown that tumor multiplicity and incidence can be decreased through the dietary administration of Protandim in the two-stage skin carcinogenesis mouse model. It has been demonstrated that cell proliferation is accommodated by cell death during DMBA/TPA treatment in the two-stage skin carcinogenesis model. Therefore, we investigated the effects of the Protandim diet on apoptosis; and proposed a novel mechanism of chemoprevention utilized by the Protandim dietary combination. Interestingly, Protandim suppressed DMBA/TPA induced cutaneous apoptosis. Recently, more attention has been focused on transcription-independent mechanisms of the tumor suppressor, p53, that mediate apoptosis. It is known that cytoplasmic p53 rapidly translocates to the mitochondria in response to pro-apoptotic stress. Our results showed that Protandim suppressed the mitochondrial translocation of p53 and mitochondrial outer membrane proteins such as Bax. We examined the levels of p53 and MnSOD expression/activity in murine skin JB6 promotion sensitive (P+) and promotion-resistant (P-) epidermal cells. Interestingly, p53 was induced only in P+ cells, not P- cells; whereas MnSOD is highly expressed in P- cells when compared to P+ cells. In addition, wild-type p53 was transfected into JB6 P- cells. We found that the introduction of wild-type p53 promoted transformation in JB6 P- cells. Our results suggest that suppression of p53 and induction of MnSOD may play an important role in the tumor suppressive activity of Protandim

    Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

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    Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which ∼20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants

    Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.

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    BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. CONCLUSIONS: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior

    Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

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    Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness

    Abstracts from the 3rd Conference on Aneuploidy and Cancer: Clinical and Experimental Aspects

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