Insufficient stress response and elevated oxidative stress can contribute to skeletal muscle atrophy during mechanical unloading (e.g., spaceflight and bedrest). Perturbations in heat shock proteins ...(e.g., HSP70), antioxidant enzymes, and sarcolemmal neuronal nitric oxidase synthase (nNOS) have been linked to unloading-induced atrophy. We recently discovered that the sarcolemmal NADPH oxidase-2 complex (Nox2) is elevated during unloading, downstream of angiotensin II receptor 1, and concomitant with atrophy. Here, we hypothesized that peptidyl inhibition of Nox2 would attenuate disruption of HSP70, MnSOD, and sarcolemmal nNOS during unloading, and thus muscle fiber atrophy. F344 rats were divided into control (CON), hindlimb unloaded (HU), and hindlimb unloaded +7.5 mg/kg/day gp91ds-tat (HUG) groups. Unloading-induced elevation of the Nox2 subunit p67phox-positive staining was mitigated by gp91ds-tat. HSP70 protein abundance was significantly lower in HU muscles, but not HUG. MnSOD decreased with unloading; however, MnSOD was not rescued by gp91ds-tat. In contrast, Nox2 inhibition protected against unloading suppression of the antioxidant transcription factor Nrf2. nNOS bioactivity was reduced by HU, an effect abrogated by Nox2 inhibition. Unloading-induced soleus fiber atrophy was significantly attenuated by gp91ds-tat. These data establish a causal role for Nox2 in unloading-induced muscle atrophy, linked to preservation of HSP70, Nrf2, and sarcolemmal nNOS.
The Asthma Predictive Index (API) and persistent wheezing phenotypes are associated with childhood asthma, but previous studies have not assessed their ability to predict objectively confirmed ...asthma.
To determine whether the University of Cincinnati API Index (ucAPI) and/or persistent wheezing at age 3 can accurately predict objectively confirmed asthma at age 7.
Data from the Cincinnati Childhood Allergy and Air Pollution Study, a high-risk prospective birth cohort, was used. Asthma was defined as parent-reported or physician-diagnosed asthma objectively confirmed by a change in FEV1 of ≥12% after bronchodilator or a positive methacholine challenge (PC20 ≤ 4 mg/mL); or as prior treatment with daily asthma controller medication(s). Multivariate logistic regression was used to investigate the relationship between confirmed asthma at age 7 and a positive ucAPI (adapted and modified from prior published API definitions) and persistent wheezing at age 3.
At age 7, 103 of 589 children (17.5%) satisfied the criteria for asthma. Confirmed asthma at age 7 was significantly associated with a positive ucAPI (adjusted odds ratio aOR 13.3 95% CI, 7.0-25.2; P < .01) and the persistent wheezing phenotype (aOR 9.8 95% CI, 4.9-19.5; P < .01) at age 3. Allergic persistent wheezing was associated with a significantly higher risk of asthma (aOR 10.4 95% CI, 4.1-26.0; P < .01) than nonallergic persistent wheezing (aOR 5.4 95% CI, 2.04-14.06; P < .01).
Both a positive ucAPI and persistent wheeze at age 3 were associated with objectively confirmed asthma at age 7; however, the highest risk was associated with ucAPI. These results demonstrate the ucAPI as a clinically useful tool for predicting future asthma in school-age children.
Skeletal muscle is a highly adaptable tissue capable of remodeling when dynamic stress is altered, including changes in mechanical loading and stretch. When muscle is subjected to an unloaded state ...(e.g., bedrest, immobilization, spaceflight) the resulting loss of muscle cross sectional area (CSA) impairs force production. In addition, muscle fiber-type shifts from slow to fast-twitch fibers. Unloading also results in a downregulation of heat shock proteins (e.g., HSP70) and anabolic signaling, which further exacerbate these morphological changes. Our lab recently showed reactive oxygen species (ROS) are causal in unloading-induced alterations in Akt and FoxO3a phosphorylation, muscle fiber atrophy, and fiber-type shift. Nutritional supplements such as fish oil and curcumin enhance anabolic signaling, glutathione levels, and heat shock proteins. We hypothesized that fish oil, rich in omega-3-fatty acids, combined with the polyphenol curcumin would enhance stress protective proteins and anabolic signaling in the rat soleus muscle, concomitant with synergistic protection of morphology. C57BL/6 mice were assigned to 3 groups (n = 6/group): ambulatory controls (CON), hindlimb unloading (HU), and hindlimb unloading with 5% fish oil, 1% curcumin in diet (FOC). FOC treatments began 10 days prior to HU and tissues were harvested following 7 days of HU. FOC mitigated the unloading induced decrease in CSA. FOC also enhanced abundance of HSP70 and anabolic signaling (Akt phosphorylation, p70S6K phosphorylation), while reducing Nox2, a source of oxidative stress. Therefore, we concluded that the combination of fish oil and curcumin prevents skeletal muscle atrophy due to a boost of heat shock proteins and anabolic signaling in an unloaded state.
In this study, we predict crystalline ordering of magnetic nanoparticles in a bilayer structure where only magnetic dipole interaction is taken into account. Estimates show that the two-dimensional ...lattice structure can be observed in the liquid nitrogen temperature regime. The results can be extended to magnetic nanoparticle multilayers. In addition, the study implies an order-disorder phase transition of the magnetic nanoparticle ensemble induced by external perpendicular magnetic fields.
Convergence of an approximate method for determining vibrational eigenpairs of an elastic solid containing an incompressible fluid is examined. The field variables are solid displacement and fluid ...pressure. We show that in suitable Sobolev spaces a variational formulation exists whose solution eigenvalues and eigenfunctions are identified with those of a compact operator. A nonconforming finite element approximation of this variational problem is described and optimal a priori error estimates are obtained for both the eigenvalues and eigenfunctions.
Genomic imprinting is an epigenetic phenomenon where autosomal genes display uniparental expression depending on whether they are maternally or paternally inherited. Genomic imprinting can arise from ...parental conflicts over resource allocation to the offspring, which could drive imprinted loci to evolve by positive selection. We investigate whether positive selection is associated with genomic imprinting in the inbreeding species Arabidopsis thaliana. Our analysis of 140 genes regulated by genomic imprinting in the A. thaliana seed endosperm demonstrates they are evolving more rapidly than expected. To investigate whether positive selection drives this evolutionary acceleration, we identified orthologs of each imprinted gene across 34 plant species and elucidated their evolutionary trajectories. Increased positive selection was sought by comparing its incidence among imprinted genes with nonimprinted controls. Strikingly, we find a statistically significant enrichment of imprinted paternally expressed genes (iPEGs) evolving under positive selection, 50.6% of the total, but no such enrichment for positive selection among imprinted maternally expressed genes (iMEGs). This suggests that maternally- and paternally expressed imprinted genes are subject to different selective pressures. Almost all positively selected amino acids were fixed across 80 sequenced A. thaliana accessions, suggestive of selective sweeps in the A. thaliana lineage. The imprinted genes under positive selection are involved in processes important for seed development including auxin biosynthesis and epigenetic regulation. Our findings support a genomic imprinting model for plants where positive selection can affect paternally expressed genes due to continued conflict with maternal sporophyte tissues, even when parental conflict is reduced in predominantly inbreeding species.
Airborne exposure to manganese (Mn) can result in neurologic effects. Stationary air sampling is the traditional technique to assess Mn exposure for communities, yet may not accurately reflect ...children's personal exposure. The goal of the study was to characterize personal exposure to Mn and PM2.5 in a cohort of children ages 7–9years residing near a ferromanganese refinery.
A subset of children living in non-smoking households ages 7–9 enrolled in the Marietta Community Actively Researching Exposure Study during March–June 2009 and 2010 were invited to participate. Blood and hair were collected and analyzed for Mn. Participants wore a PM2.5 sampler (Personal Modular Impactor) for 48h. TWD was based on time spent at home and school and the distance of each from the refinery. Stationary outdoor air sampling was conducted 8km from the refinery using a Harvard-type PM2.5 impactor. The relationship between personal Mn exposure and TWD was examined by multiple regression adjusting for stationary air Mn concentration, wind speed and direction, and precipitation.
Complete personal air sampling data were collected on 38 children. TWD ranged from 4.7km to 28.5km with a mean distance of 11.1 (4.7sd) km. Mn concentration in personal air samples ranged from 1.5ng/m3 to 54.5ng/m3 (geometric mean, 8.1ng/m3). TWD was a significant predictor of natural log personal air Mn concentration (lnMn) with an associated decrease of 0.075lnMn for each km TWD (p<0.05, 95% CI −0.13 to −0.01). Personal Mn exposures were positively associated with stationary air Mn levels and inversely associated with wind speed.
A child's location (home and school) relative to the refinery is a significant predictor of personal Mn exposure. Wind speed is also an important contributor to personal Mn exposure.
► Personal air sampling on 38 children residing near a ferromanganese refinery ► Personal Mn ranged from 1.5ng/m3 to 54.5ng/m3. ► TWD was a significant predictor of ln personal air Mn concentration. ► Personal Mn positively associated with stationary air Mn ► Wind speed also contributed to personal Mn exposure.
The houses, kitchens, barns, stables and cowsheds of the rural area of the parish of Ingatestone are described as they were in the second half of the sixteenth century. Various aspects of the ...building activity which took place in the parish during this period are discussed and it is concluded that this peak in a continuum of modernisation should be termed a 'Housing Revolution' rather than a 'Great Rebuilding'.
During 2009-2010, we examined 217 patients hospitalized with laboratory-confirmed pandemic influenza in 9 Influenza Hospitalization Surveillance Network sites and 413 age- and community-matched ...controls and found that a single dose of monovalent nonadjuvanted influenza A(H1N1)pdm09 vaccine was 50% (95% confidence interval, 13%-71%) effective in preventing hospitalization associated with A(H1N1)pdm09 virus infection.
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