MicroRNA-155 (miR-155) is frequently upregulated in various types of human cancer; however, its role in cancer angiogenesis remains unknown. Here, we demonstrate the role of miR-155 in angiogenesis ...through targeting von Hippel-Lindau (VHL) tumour suppressor in breast cancer. Ectopic expression of miR-155 induced whereas knockdown of miR-155 inhibited human umbilical vein endothelial cell network formation, proliferation, invasion and migration. Furthermore, mammary fat pad xenotransplantation of ectopically expressed miR-155 resulted in extensive angiogenesis, proliferation, tumour necrosis and recruitment of pro-inflammatory cells such as tumour-associated macrophages. Expression of VHL abrogated these miR-155 effects. Moreover, miR-155 expression inversely correlates with VHL expression level and is associated with late-stage, lymph node metastasis and poor prognosis, as well as triple-negative tumour in breast cancer. These findings indicate that miR-155 has a pivotal role in tumour angiogenesis by downregulation of VHL, and provide a basis for miR-155-expressing tumours to embody an aggressive malignant phenotype, and therefore miR-155 is an important therapeutic target in breast cancer.
Ninety-four cows were randomly allocated to 1 of 5 stocking rates (2.2, 2.7, 3.1, 3.7, and 4.3 cows/ha) in a completely randomized design for 3 years. Herds were seasonal calving, with only minor ...differences in grazing management to optimize the profitability of each stocking rate (SR). Pasture production and quality data, milk and milk component data, and reproduction data were collected, averaged for SR treatment, and linear and quadratic contrasts on SR were evaluated. In addition, the Wilmink exponential model (yt=a + b×e(−0.05t) + c×t) was fitted to milk yield within lactation, and the parameters were averaged by SR treatment and analyzed as above. The median variation explained by the function for individual lactations was 84%. The amount of pasture grown tended to increase, and the quality of the pasture on offer increased linearly with increasing SR, reducing some of the negative impact of SR on the availability of pasture per cow. Milk production per cow declined linearly with increasing SR, although there was a tendency for most production variables to decline quadratically, with the negative effect of SR declining with increasing SR. The effect on milk production per cow was primarily because of a lower peak milk yield and a greater post-peak decline (less persistent milk profile), although a decline in lactation length with increasing SR was responsible for 24% of the effect of SR on milk yield. Milk production per hectare increased linearly with increasing SR, and there was only a small difference (approximately 3%/cow per ha) in the efficiency of converting feed dry matter into milk energy. Stocking rate did not affect reproductive success. The data are consistent with the need for a more robust measure of SR than cows per hectare because farms will differ in the genetic merit of their cows and in the potential to produce pasture. We introduce the concept of a comparative SR, whereby the carrying capacity of the farm is defined by the BW of the cows, the potential of the land to produce pasture, and the amount of supplement purchased (kg of BW/t of feed dry matter). The adoption of such a measure would facilitate the extrapolation and transfer of research findings among systems.
Abstract Determining the time of peak of cerebral maturation is vital for our understanding of when cerebral maturation ceases and the cerebral degeneration in healthy aging begins. We carefully ...mapped changes in fractional anisotropy (FA) of water diffusion for eleven major cerebral white matter tracts in a large group (831) of healthy human subjects aged 11–90. FA is a neuroimaging index of micro-structural white matter integrity, sensitive to age-related changes in cerebral myelin levels, measured using diffusion tensor imaging. The average FA values of cerebral white matter (WM) reached peak at the age 32 ± 6 years. FA measurements for all but one major cortical white matter tract (cortico-spinal) reached peaks between 23 and 39 years of age. The maturation rates, prior to age-of-peak were significantly correlated ( r = 0.74; p = 0.01) with the rates of decline, past age-of-peak. Regional analysis of corpus callosum (CC) showed that thinly-myelinated, densely packed fibers in the genu, that connect pre-frontal areas, maturated later and showed higher decline in aging than the more thickly myelinated motor and sensory areas in the body and splenium of CC. Our findings can be summarized as: associative, cerebral WM tracts that reach their peak FA values later in life also show progressively higher age-related decline than earlier maturing motor and sensory tracts. These findings carry multiple and diverse implications for both theoretical studies of the neurobiology of maturation and aging and for the clinical studies of neuropsychiatric disorders.
Production from pasture-based dairy farms can be increased through using N fertilizer to increase pasture grown, increasing stocking rate, importing feeds from off farm (i.e., supplementary feeds, ...such as cereal silages, grains, or co-product feeds), or through a combination of these strategies. Increased production can improve profitability, provided the marginal cost of the additional milk produced is less than the milk price received. A multiyear production system experiment was established to investigate the biological and economic responses to intensification on pasture-based dairy farms; 7 experimental farmlets were established and managed independently for 3 yr. Paddocks and cows were randomly allocated to farmlet, such that 3 farmlets had stocking rates of 3.35 cows/ha (LSR) and 4 farmlets had stocking rates of 4.41 cows/ha (HSR). Of the LSR farmlets, 1 treatment received no N fertilizer, whereas the other 2 received either 200 or 400 kg of N/ha per year (200N and 400N, respectively). No feed was imported from off-farm for the LSR farmlets. Of the 4 HSR farmlets, 3 treatments received 200N and the fourth treatment received 400N; cows on 2 of the HSR-200N farmlet treatments also received 1.3 or 1.1 t of DM/cow per year of either cracked corn grain or corn silage, respectively. Data were analyzed for consistency of farmlet response over years using mixed models, with year and farmlet as fixed effects and the interaction of farmlet with year as a random effect. The biological data and financial data extracted from a national economic database were used to model the statement of financial performance for the farmlets and determine the economic implications of increasing milk production/cow and per ha (i.e., farm intensification). Applying 200N or 400N increased pasture grown per hectare and milk production per cow and per hectare, whereas increasing stocking rate did not affect pasture grown or milk production per hectare, but reduced milk production per cow. Importing feed in the HSR farmlets increased milk production per cow and per hectare. Marginal milk production responses to additional feed (i.e., either pasture or imported supplementary feed) were between 0.8 and 1.2 kg of milk/kg of DM offered (73 to 97 g of fat and protein/kg of feed DM) and marginal response differences between feeds were explained by metabolizable energy content differences (0.08 kg of milk/MJ of metabolizable energy offered). The marginal milk production response to additional feed was quadratic, with the greatest milk production generated from the initial investment in feed; 119, 99, and 55 g of fat and protein were produced per kilogram of feed DM by reducing the annual feed deficit from 1.6 to 1.0, 1.0 to 0.5, and 0.5 to 0 t of DM, respectively. Economic modeling indicated that the marginal cost of milk produced from pasture resulting from applied N fertilizer was less than the milk price; therefore, strategic use of N fertilizer to increase pasture grown increased farm operating profit per hectare. In comparison, operating profit declined with purchased feed, despite high marginal milk production responses. The results have implications for the strategic direction of grazing dairy farms, particularly in export-oriented industries, where the prices of milk and feed inputs are subject to the considerable volatility of commodity markets.
Many DNP scholarly projects occur in healthcare organizations, often taking various forms based on specific academic requirements. Projects require site mentorship, project facilitation, and ...institutional review board resources. This article highlights the impact of DNP scholarly projects on healthcare organizations and provides a road map for success for healthcare leaders and site mentors.
We examined age trajectories of fractional anisotropy (FA) of cerebral white matter (WM) and thickness of cortical gray matter (GM) in 1031 healthy human subjects (aged 11–90
years). Whole-brain FA ...and GM thickness values followed quadratic trajectories with age but the relationship between them was linear, indicating that a putative biological mechanism may explain the non-linearity of their age trajectories. Inclusion of the FA values into the quadratic model of the whole-brain and regional GM thickness changes with age made the effect of the age
2 term no longer significant for the whole-brain GM thickness and greatly reduced its significance for regional GM thickness measurements. The phylogenetic order of cerebral myelination helped to further explain the intersubject variability in GM thickness. FA values for the early maturing WM were significantly better (p
=
10
−
6
) at explaining variability in GM thickness in maturing (aged 11–20) subjects than FA values for the late maturing WM. The opposite trend was observed for aging subjects (aged 40–90) where FA values for the late maturing WM were better (p
=
10
−
16
) at explaining the variability in GM thickness. We concluded that the non-linearity of the age trajectory for GM thickness, measured from T1-weighted MRI, was partially explained by the heterogeneity and the heterochronicity of the age-related changes in the microintegrity of cerebral WM. We consider these findings as the evidence that the measurements of age-related changes in GM thickness and FA are driven, in part, by a common biological mechanism, presumed to be related to changes in cerebral myelination.
► Age-trajectories of DTI-FA and GM thickness were mapped in 1031 subjects aged 11–90. ► FA and GM thickness values followed quadratic trajectories with age. ► FA values partially explained the non-linearity of GM age trajectory. ► Changes in GM thickness and FA with age are driven, in part, by a common mechanism. ► This mechanism is presumed to be related to changes in cerebral myelination.
Recent progress in the development of barium strontium titanate thin film varactors for room temperature tunable microwave devices applications is reviewed, with emphasis on efforts towards the ...improvement in the quality of BST thin films and the fabrication issues crucial for the performance of microwave devices based on BST varactors. The paper provides examples of tunable microwave devices employing BST varactors. Other thin film materials currently competing with BST thin films are discussed. Topics which deserve further investigation are suggested.
African Americans, especially women, have higher obesity rates than the general US population. Because of the importance of faith to many African Americans, faith‐based organizations (FBOs) may be ...effective venues for delivering health messages and promoting adoption of healthy behaviours. This article systematically reviews interventions targeting weight and related behaviours in faith settings. We searched literature published through July 2012 for interventions in FBOs targeting weight loss, diet and/or physical activity (PA) in African Americans. Of 27 relevant articles identified, 12 were randomized controlled trials; seven of these reported a statistically significant change in an outcome. Four of the five quasi‐experimental and single‐group design studies reported a statistically significant outcome. All 10 pilot studies reported improvement in at least one outcome, but most did not have a comparison group. Overall, 70% of interventions reported success in reducing weight, 60% reported increased fruit and vegetable intake and 38% reported increased PA. These results suggest that interventions in African American FBOs can successfully improve weight and related behaviours. However, not all of the findings about the success of certain approaches were as expected. This review identifies gaps in knowledge and recommends more rigorous studies be conducted to strengthen the comparative methodology and evidence.
There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an ...allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45
immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.
Data from a multiyear farm systems study evaluating the effect of stocking rate (SR) on pasture production and utilization, milk production per cow and per hectare, reproduction, and cow health were ...used to determine the economic implications of altering SR. The effect of SR was also evaluated relative to cow size and total feed available (comparative stocking rate; CSR), to account for differences in cow size and feed supplement availability. Milk production, gross revenue, operating expenses, and operating profit per cow all declined with increasing SR and CSR. In comparison, milk production, gross revenue, and operating expenses per hectare increased with increasing SR and CSR. These effects were irrespective of milk price. The effect of SR on operating profit and return on assets, however, was dependent on milk payment system. When payment was based on the economic value of milk fat and protein, operating profit and return on assets were quadratically associated with both SR and CSR, declining at an SR greater or less than 3.3 cows/ha and a CSR greater or less than 77kg of body weight/t of feed dry matter available. In comparison, when milk payment was based on a fluid milk pricing system, profit per hectare increased linearly with increasing SR and CSR, but return on assets was not affected by SR or CSR.
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