We aimed to describe and characterize the gut microbiota composition and diversity in children with obesity according to their metabolic health status.
Anthropometry, Triglycerides, HDL cholesterol, ...HOMA-IR, and systolic and diastolic blood pressure (SBP, DBP) were evaluated (and z-score calculated) and faecal samples were collected from 191 children with obesity aged from 8 to 14. All children were classified depending on their cardiometabolic status in either a “metabolically healthy” (MHO; n = 106) or “metabolically unhealthy” (MUO; n = 85) group. Differences in gut microbiota taxonomies and diversity between groups (MUO vs MHO) were analysed. Alpha diversity index was calculated as Chao1 and Simpson’s index, and β-diversity was calculated as Adonis Bray–Curtis index. Spearman’s correlations and logistic regressions were performed to study the association between cardiometabolic health and the microbiota.
Children in the MUO presented significantly lower alpha diversity and richness than those in the MHO group (Chao1 index p = 0.021, Simpson’s index p = 0.045, respectively), whereas microbiota β-diversity did not differ by the cardiometabolic health status (Adonis Bray–Curtis, R2 = 0.006; p = 0.155). The MUO group was characterized by lower relative abundances of the genera Christensenellaceae R7 group (MHO:1.42% 0.21–2.94; MUO:0.47% 0.02–1.60, p < 0.004), and Akkermansia (MHO:0.26% 0.01–2.19; MUO:0.01% 0.00–0.36, p < 0.001) and higher relative abundances of Bacteroides (MHO:10.6% 4.64–18.5; MUO:17.0% 7.18–27.4, p = 0.012) genus. After the adjustment by sex, age, and BMI, higher Akkermansia (OR: 0.86, CI: 0.75–0.97; p = 0.033), Christensenellaceae R7 group (OR: 0.86, 95% CI: 075–0.98; p = 0.031) and Chao1 index (OR: 0.86, CI: 0.96–1.00; p = 0.023) represented a lower risk of the presence of one or more altered cardiovascular risk factors.
Lower proportions of Christensenellaceae and Akkermansia and lower diversity and richness seem to be indicators of a metabolic unhealthy status in children with obesity.
Loss of myofilaments has been observed in both adaptive cardiac responses (i.e., hypertrophy) as well as in chemotheraputic use of antineoplastic drugs with cardiotoxic side effects (i.e., ...doxorubicin). An understanding of the degenerative process is a prerequisite for determining approaches to limit the cardiomyopathic changes associated with chronic heart disease or long-term chemotheraputic treatments. However, little is known about the specific events and molecular changes that initiate the degenerative process. To study this process, neonatal rat cardiomyocytes were treated with doxorubicin, which induced rapid and widespread thin-filament degeneration as observed by fluorescence confocal microscopy. Which demonstrated deterioration of sarcomeric thin-filament structure. Changes in the spontaneous beating of cardiomyocytes corresponding with myofibrillar degeneration were apparent using differential interference contrast video microscopy. After finding induction of kinase activity by doxorubicin in cultured cardiomyocytes, the protective effects of specific inhibitors of kinase activity were assessed for their ability to inhibit doxorubicin-induced myofibrillar break-down. Doxorubicin-induced changes appeared similar to the degeneration observed after treatment with a protein kinase activator (phorbol 12-myristate 13-acetate) or a serine-threonine protein phosphatase inhibitor (okadaic acid). Collectively, these results indicate that activation of protein kinase is an important event in the initiation of myofibrillar degeneration by doxorubicin. Further analyses of myofibrillar proteins with respect to biochemical modifications will be necessary to determine if phosphorylation events transmit signal(s) to initiate degeneration.
To understand how protein phosphorylation modulates cytoskeletal organization, we used immunofluorescence microscopy to examine the effects of okadaic acid, a serine/threonine protein phosphatase ...inhibitor, and taxol, a microtubule-stabilizing agent, on stable (acetylated and detyrosinated) microtubules, vimentin intermediate filaments and other cytoskeletal elements in CV-1 cells. Okadaic acid caused major changes in both stable microtubules and vimentin intermediate filaments, but through independent mechanisms. At 300 nM, okadaic acid caused apparent fragmentation and loss of stable microtubules which was not prevented by prior exposure to K252a. In contrast, major reorganization of vimentin intermediate filaments elicited at 750 nM okadaic acid was prevented by prior exposure to K252a. Taxol pretreatment blocked the effects of okadaic acid on stable microtubules and vimentin intermediate filaments. Recent reports have revealed that taxol can activate cellular signal transduction pathways in addition to its known ability to promote microtubule stabilization, so the possibility that taxol-induced resistance of vimentin intermediate filaments to okadaic acid was through a microtubule-independent mechanism involving direct phosphorylation of intermediate filament proteins was explored. Vimentin immunoprecipitation from cytoskeletal extracts from 32P-labeled cells revealed that taxol (4 microM, 1 or 2 hours) caused about a 2-fold increase in vimentin phosphorylation. This phosphorylation was recovered exclusively in cytoskeletal vimentin, in contrast to the increased phosphorylation of soluble and cytoskeletal vimentin caused by exposure to 750 nM okadaic acid. Phosphorylation of soluble and cytoskeletal vimentin from cells exposed to taxol (4 microM, 1 hour) then okadaic acid (750 nM, 1 hour) was comparable to taxol-treatment alone. These findings demonstrate a novel new activity of taxol, induction of vimentin phosphorylation, that may impact on vimentin organization and stability.
Anti-topoisomerase II agents represent a major class of anticancer therapeutic agents. Resistance to this class of agents can be mediated by several possible mechanisms. One mechanism may involve ...mutations in the structural gene(s) for topoisomerases, altering the drug sensitivity of the enzymes. Several mutations have been described in mammalian cell lines that were selected for resistance to topoisomerase II-targeting drugs such as Adriamycin, etoposide, or amsacrine. The difficulty of performing genetic analysis in mammalian cell lines has complicated the determination of whether the observed mutations are responsible for drug resistance. We have reconstructed, in the yeast topoisomerase II gene, the arginine to glutamine mutation at position 450 of human topoisomerase II alpha that was originally identified by Bugg et al. Proc. Natl. Acad. Sci. USA 88:7654-7658 (1991). Mutation of Lys439, the equivalent amino acid in the yeast protein, to either glutamine or glutamic acid confers resistance to etoposide and amsacrine. Interestingly, in diploid yeast cells the heterozygous mutation can still confer partial drug resistance, compared with a diploid strain that is homozygous for wild-type topoisomerase II. Because mutations in the topoisomerase II gene that can confer dominant resistance to anti-topoisomerase II agents are relatively rare, mutations in the gyrB region may be important in the development of clinical drug resistance.
The variation of maximal respiratory pressures (
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imax and
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emax) in healthy subjects were studied on the same day in 16 non-smoking healthy men (age 26·2 ± 3·2 years). The
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imax and
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emax were ...obtained on three occasions (8 a.m., 2 p.m. and 9 p.m.) within the same day. There were no differences between readings for
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imax and
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emax values.
Model–data comparisons of plant physiological processes provide an understanding of mechanisms underlying vegetation responses to climate. We simulated the physiology of a piñon pine–juniper woodland ...(Pinus edulis–Juniperus monosperma) that experienced mortality during a 5 yr precipitation-reduction experiment, allowing a framework with which to examine our knowledge of drought-induced tree mortality. We used six models designed for scales ranging from individual plants to a global level, all containing state-of-the-art representations of the internal hydraulic and carbohydrate dynamics of woody plants. Despite the large range of model structures, tuning, and parameterization employed, all simulations predicted hydraulic failure and carbon starvation processes co-occurring in dying trees of both species, with the time spent with severe hydraulic failure and carbon starvation, rather than absolute thresholds per se, being a better predictor of impending mortality. Model and empirical data suggest that limited carbon and water exchanges at stomatal, phloem, and below-ground interfaces were associated with mortality of both species. The model–data comparison suggests that the introduction of a mechanistic process into physiology-based models provides equal or improved predictive power over traditional process-model or empirical thresholds. Both biophysical and empirical modeling approaches are useful in understanding processes, particularly when the models fail, because they reveal mechanisms that are likely to underlie mortality. We suggest that for some ecosystems, integration of mechanistic pathogen models into current vegetation models, and evaluation against observations, could result in a breakthrough capability to simulate vegetation dynamics.
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