The Focal Adhesion Kinase Suppresses Transformation-associated, Anchorage-independent Apoptosis in Human Breast Cancer Cells: INVOLVEMENT OF DEATH RECEPTOR-RELATED SIGNALING PATHWAYS

The focal adhesion kinase (FAK) is a mediator of cell-extracellular matrix signaling events and is overexpressed in tumor cells. In order to rapidly down-regulate FAK function in normal and transformed mammary cells, we have used adenoviral gene transduction of the carboxyl-terminal domain of FAK (FAK-CD). Transduction of adenovirus containing FAK-CD in breast cancer cells caused loss of adhesion, degradation of p125(FAK), and induced apoptosis. Furthermore, breast tumor cells that were viable without matrix attachment also underwent apoptosis upon interruption of FAK function, demonstrating that FAK is a survival signal in breast tumor cells even in the absence of matrix signaling. In addition, both anchorage-dependent and anchorage-independent apoptotic signaling required Fas-associated death domain and caspase-8, suggesting that a death receptor-mediated apoptotic pathway is involved. Finally, FAK-CD had no effect on adhesion or viability in normal mammary cells, despite the loss of tyrosine phosphorylation of p125(FAK). These results indicate that FAK-mediated signaling is required for both cell adhesion and anchorage-independent survival and the disruption of FAK function involves the Fas-associated death domain and caspase-8 apoptotic pathway

High-Sensitivity Cardiac Troponin-I Is Elevated in Patients with Rheumatoid Arthritis, Independent of Cardiovascular Risk Factors and Inflammation

We examined the hypothesis that cardiac-specific troponin-I (cTn-I), a biomarker of myocardial injury, is elevated in patients with rheumatoid arthritis (RA).RA patients have an increased incidence of heart failure (HF). Chronic myocardial injury in RA may be a mechanism for the development of HF.We compared cTn-I concentrations measured by high-sensitivity immunoassay in 164 patients with RA and 90 controls, excluding prior or active heart failure. We examined the relationship between cTn-I concentrations and cardiovascular risk factors, inflammation, and coronary artery calcium score (CACS), a measure of coronary atherosclerosis.cTn-I concentrations were 49% higher in patients with RA (median 1.15 pg/mL [IQR 0.73–1.92] than controls (0.77 pg/mL [0.49–1.28](P<0.001). The difference remained statistically significant after adjustment for demographic characteristics (P = 0.002), further adjustment for cardiovascular (CV) risk factors (P = 0.004), inflammatory markers (P = 0.008), and in a comprehensive model of CV risk factors and inflammatory markers (P = 0.03). In patients with RA, cTn-I concentrations were positively correlated with age (rho = 0.359), Framingham risk score (FRS) (rho = 0.366), and systolic blood pressure (rho = 0.248 (all P values ≤0.001)), but not with measures of inflammation or RA drug therapies. cTn-I was significantly correlated with CACS in RA in univariate analysis, but not after adjustment for age, race, sex and FRS (P = 0.79). Further model adjustments for renal function and coronary artery disease confirmed the significance of the findings.High-sensitivity cTn-I concentrations are elevated in patients with RA without heart failure, independent of cardiovascular risk profile and inflammatory markers. Elevated troponin concentrations in RA may indicate subclinical, indolent myocardial injury

Spatial isotopic dietary plasticity of a Neotropical forest ungulate: the white-lipped peccary (Tayassu pecari)

White-lipped peccaries (WLPs; Tayassu pecari, Tayassuidae, Cetartiodactyla) are forest-dwelling ungulates critical to maintaining healthy Neotropical forest ecosystems through key aspects of their dietary behaviors, including seed predation and dispersal. Land-use change and deforestation threaten WLP access to food resources, and thus knowledge of how WLP diet varies spatially is necessary to frame conservation efforts for the species. Here, we use stable carbon (δ13C) and nitrogen (δ15N) isotopes from WLP hair and food resources to assess whether WLP diet varies among four regions in three Brazilian biomes: the Pantanal, the Cerrado, and the Atlantic Forest (semi-deciduous and ombrophilous), each varying in forest canopy cover, climatic characteristics, and degrees of agricultural impacts. We find that in all regions WLPs are consuming primarily C3 resources, with mean δ13C values ranging from –28.7‰ to –26.9‰. In the heavily fragmented semi-deciduous Atlantic Forest, δ13C values are the highest, and may indicate that some individuals are consuming a small amount of C4 crops or demonstrating increased levels of insectivory. A through-time comparison of WLP hair in the semi-deciduous Atlantic Forest suggests the recorded slight departure from an exclusive C3 diet may be a recent phenomenon, as hairs collected prior to the year 2000 have lower δ13C values than those collected in 2016. While some individual WLPs may slightly alter diet in heavily anthropogenically modified areas, C4 crops are not a main component of WLP diet. Our results suggest that WLPs are still highly dependent on forest resources, even in human-altered landscapes, and conservation and management plans for the species must consider these dietary needs in order to be successful

Correlation between hs-cTn-I and clinical variables in patients with RA and controls.

*<p>P values by Spearman’s correlation coefficient test.</p

Multivariable Linear Regression Troponin Models for RA Patients vs Controls.

<p>Model 1: Adjusted for patient age, race, gender (p = 0.002)<b>;</b> Model 2: Adjusted for age, race, gender, and cardiovascular risk factors (p = 0.004); Model 3: Adjusted for age, race, gender and markers of inflammation (p = 0.008); Model 4: Adjusted for age, race, gender, cardiovascular risk factors, markers of inflammation, and NT-proBNP (p = 0.03).</p

Concentrations of hs-cTn-I in patients with RA receiving different drugs (n = 164).

*<p>Wilcoxon’s rank sum test.</p