1,842 research outputs found

    CONCENTRATION ISSUES IN THE U.S. BEEF SUBSECTOR

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    Industrial Organization, Livestock Production/Industries,

    Inhibition of protein geranylgeranylation induces apoptosis in synovial fibroblasts

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    Statins, competitive inhibitors of hydroxymethylglutaryl-CoA reductase, have recently been shown to have a therapeutic effect in rheumatoid arthritis (RA). In RA, synovial fibroblasts in the synovial lining, are believed to be particularly important in the pathogenesis of disease because they recruit leukocytes into the synovium and secrete angiogenesis-promoting molecules and proteases that degrade extracellular matrix. In this study, we show a marked reduction in RA synovial fibroblast survival through the induction of apoptosis when the cells were cultured with statins. Simvastatin was more effective in RA synovial fibroblasts than atorvastatin, and both statins were more potent on tumor necrosis factor-α-induced cells. In contrast, in osteoarthritis synovial fibroblasts, neither the statin nor the activation state of the cell contributed to the efficacy of apoptosis induction. Viability of statin-treated cells could be rescued by geranylgeraniol but not by farnesol, suggesting a requirement for a geranylgeranylated protein for synovial fibroblast survival. Phase partitioning experiments confirmed that in the presence of statin, geranylgeranylated proteins are redistributed to the cytoplasm. siRNA experiments demonstrated a role for Rac1 in synovial fibroblast survival. Western blotting showed that the activated phosphorylated form of Akt, a protein previously implicated in RA synovial fibroblast survival, was decreased by about 75%. The results presented in this study lend further support to the importance of elevated pAkt levels to RA synovial fibroblast survival and suggest that statins might have a beneficial role in reducing the aberrant pAkt levels in patients with RA. The results may also partly explain the therapeutic effect of atorvastatin in patients with RA

    The genetic basis for adaptation of model-designed syntrophic co-cultures.

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    Understanding the fundamental characteristics of microbial communities could have far reaching implications for human health and applied biotechnology. Despite this, much is still unknown regarding the genetic basis and evolutionary strategies underlying the formation of viable synthetic communities. By pairing auxotrophic mutants in co-culture, it has been demonstrated that viable nascent E. coli communities can be established where the mutant strains are metabolically coupled. A novel algorithm, OptAux, was constructed to design 61 unique multi-knockout E. coli auxotrophic strains that require significant metabolite uptake to grow. These predicted knockouts included a diverse set of novel non-specific auxotrophs that result from inhibition of major biosynthetic subsystems. Three OptAux predicted non-specific auxotrophic strains-with diverse metabolic deficiencies-were co-cultured with an L-histidine auxotroph and optimized via adaptive laboratory evolution (ALE). Time-course sequencing revealed the genetic changes employed by each strain to achieve higher community growth rates and provided insight into mechanisms for adapting to the syntrophic niche. A community model of metabolism and gene expression was utilized to predict the relative community composition and fundamental characteristics of the evolved communities. This work presents new insight into the genetic strategies underlying viable nascent community formation and a cutting-edge computational method to elucidate metabolic changes that empower the creation of cooperative communities

    Beetles in bamboo forests: community structure in a heterogeneous landscape of southwestern Amazonia

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    Amazonian bamboo forests dominated by large woody bamboo plants in the genus Guadua cover approximately 180,000 km2 and represent a key resource for many organisms. In southwestern Amazonia, native bamboo forests differ in structure, biodiversity, and growth dynamics from other forest types in the region. However, with the exception of a few species in which habitat specialization or a strong habitat association has been demonstrated, little is known about how bamboo forests influence animal community structure. In an effort to understand more about the animal assemblages associated with Amazonian bamboo forests, we characterized the structure of ground-dwelling beetle assemblages living in bamboo forests and adjacent terra firme forests in a lowland rainforest site in Peru. We conducted intensive pitfall trap surveys in 13 bamboo habitat patches and 13 adjacent terra firme habitat patches to determine if there were differences in the abundance and richness of beetle species in these two habitat types. Additionally, given that southwestern Amazonia experiences distinct dry and wet seasons, we conducted our study during the dry and wet season of one year to account for differences in seasonality. We found a distinct beetle assemblage associated with each forest type, and identified a set of dominant species that significantly contributed to the distinctness in beetle community structure between bamboo and terra firme forest. The terra firme forest had a greater number of rare species than the bamboo forest. Several beetle species exhibited a strong association with the bamboo forest, including a large species of Scarabaeidae that appears to be specializing on bamboo. We also found marked differences in beetle assemblages between dry and wet seasons. Our results support the prediction that beetle community structure in bamboo forest differs from that of terra firme in terms of species richness, abundance, and composition. Bamboo-associated animal communities require more exploration and study, and must be included in regional conservation plans seeking to protect entire animal communities in southwestern Amazonia

    Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance

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    Aims To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence. Methods We used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years. Results In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95% confidence interval) for diabetes in those with MetS (vs. no MetS) at baseline were 1.7 (1.3–2.3), 1.7 (1.2–2.3) and 2.0 (1.3–3.0) for placebo, metformin and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favourable changes in WC (placebo and lifestyle) and high-density lipoprotein cholesterol (placebo and metformin) contributed to reduced diabetes risk. Conclusions MetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycaemia, the most predictive factors for diabetes were baseline hypertriglyceridaemia and both baseline and lifestyle-associated changes in WC. Targeting these cardiometabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence

    Ballooning Instability in Polar Caps of Accreting Neutron Stars

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    We assess the stability of Kruskal-Schwarzschild (magnetic Rayleigh-Taylor) type modes for accreted matter on the surface of a neutron star confined by a strong (>= 1.E12 G) magnetic field. Employing the energy principle to analyze the stability of short-wavelength ballooning modes, we find that line-tying to the neutron star crust stabilizes these modes until the overpressure at the top of the neutron star crust exceeds the magnetic pressure by a factor ~ 8(a/h), where a and h are respectively the lateral extent of the accretion region and the density scale height. The most unstable modes are localized within a density scale height above the crust. We calculate the amount of mass that can be accumulated at the polar cap before the onset of instability.Comment: 8 pages, 2 figures, accepted for publication by ApJ, uses AASTEX 5.0 and emulateapj5.sty (included

    Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance

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    AIMS: To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence. METHODS: We used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years. RESULTS: In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95% confidence interval) for diabetes in those with MetS (vs. no MetS) at baseline were 1.7 (1.3-2.3), 1.7 (1.2-2.3) and 2.0 (1.3-3.0) for placebo, metformin and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favourable changes in WC (placebo and lifestyle) and high-density lipoprotein cholesterol (placebo and metformin) contributed to reduced diabetes risk. CONCLUSIONS: MetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycaemia, the most predictive factors for diabetes were baseline hypertriglyceridaemia and both baseline and lifestyle-associated changes in WC. Targeting these cardiometabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence

    An Australian longitudinal pilot study examining health determinants of cardiac outcomes 12 months post percutaneous coronary intervention

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    Background Percutaneous coronary intervention (PCI) is a very common revascularisation procedure for coronary artery disease (CAD). The purpose of this study was to evaluate cardiac outcomes, health related quality of life (HRQoL), resilience and adherence behaviours in patients who have undergone a PCI at two time points (6 and 12 months) following their procedure. Methods A longitudinal pilot study was conducted to observe the cardiac outcomes across a cohort of patients who had undergone a percutaneous coronary intervention (PCI). Participants who had undergone PCI 6 months prior were invited. Those participants who met the inclusion criteria and provided consent then completed a telephone survey (time point 1). These participants were then contacted 6 months later (i.e. 12 months post-intervention, time point 2) and the measures were repeated. Results All patients (n = 51) were recorded as being alive at time point 1. The multiple model indicated that controlling for other factors, gender was significantly associated with a linear combination of outcome measures (p = 0.004). The effect was moderate in magnitude (partial-η2 = 0.303), where males performed significantly better than females 6 months after the PCI procedure physically and with mood. Follow-up univariate ANOVAs indicated that gender differences were grounded in the scale measuring depression (PHQ9) (p = 0.005) and the physical component score of the short form measuring HRQoL (SF12-PCS) (p = 0.003). Thirteen patients were lost to follow-up between time points 1 and 2. One patient was confirmed to have passed away. The pattern of correlations between outcome measures at time point 2 revealed statistically significant negative correlation between the PHQ instrument and the resilience scale (CD-RISC) (r = -0.611; p < 0.001); and the physical component score of the SF-12 instrument (r = -0.437; p = 0.054). Conclusions Men were performing better than women in the 6 months post-PCI, particularly in the areas of mood (depression) and physical health. This pilot results indicate gender-sensitive practices are recommended particularly up to 6 months post-PCI. Any gender differences observed at 6 month appear to disappear at 12 months post-PCI. Further research into the management of mood particularly for women post-PCI is warranted. A more detailed inquiry related to access/attendance to secondary prevention is also warranted
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