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Cattle living at altitudes greater than 1,500 m are susceptible to the development of high altitude disease (HAD) and a higher risk of death. Pulmonary arterial pressure (PAP) is used as an indicator of an animal's susceptibility to HAD. Measurements of PAP on cattle at lower elevations are generally considered less reliable indicators of HAD when compared to measurements taken at higher elevations, yet little evidence has been published evaluating this relationship. Therefore, the objective of this study was to evaluate PAP measurements from high and low elevations using a multivariate approach. We hypothesized that PAP measurements from lower elevations have a less than perfect relationship to PAP measurements from high elevations. Data collected from 2009 to 2017 was obtained from a multi-breed seedstock database that included PAP measurements and associated information (i.e., PAP testing date and elevation). The average PAP measurement was 44.08 ± 10.75 mmHg, with minimum and maximum observations of 32 and 149 mmHg, respectively. The age when PAP measurements were taken ranged from 9 to 21 months with an average age of 15.9 ± 2.8 months. Elevation ranged from 1,555 m to 2,407 m with a bimodal distribution. Therefore, animals with PAP measurements from elevations above 2,000 m were classified as high elevation (HPAP; n = 1,369) and animals with PAP measurements below 2,000 m were considered low elevation (LPAP; n = 1,243). A two-trait animal model was used to estimate genetic parameters and EBV for both LPAP and HPAP traits. The model contained the fixed effects of degree of outcross, breed percent, and PAP age as covariates, and sex and contemporary group (PAP date and yearling management combined) categories. Breed effects were included as covariates of breed percentages for Angus, Charolais, South Devon, Gelbvieh, Simmental, and "Other" breeds. Animal was included as a random effect and a 3-generation pedigree consisting of 11,573 animals was used. Heritability for LPAP and HPAP were 0.26 ± 0.08 and 0.37 ± 0.10, respectively, with a genetic correlation of 0.79 ± 0.23. Sire EBV for HPAP were regressed on corresponding sire EBV for LPAP, resulting in a regression coefficient of 0.705 ± 0.002 (P < 0.0001). These results suggest that a strong relationship exists between LPAP and HPAP, but the relationship is not perfect. The high genetic correlation between the traits suggest that measurements taken at lower elevations can still serve as an indicator of PAP measurements collected at higher elevations. [ABSTRACT FROM AUTHOR]

Tunneling nanotubes (TNTs) are actin-based membranous structures bridging distant cells for intercellular communication. We define roles for TNTs in stress adaptation and treatment resistance in prostate cancer (PCa). Androgen receptor (AR) blockade and metabolic stress induce TNTs, but not in normal prostatic epithelial or osteoblast cells. Co-culture assays reveal enhanced TNT formation between stressed and unstressed PCa cells as well as from stressed PCa to osteoblasts. Stress-induced chaperones clusterin and YB-1 localize within TNTs, are transported bi-directionally via TNTs and facilitate TNT formation in PI3K/AKT and Eps8-dependent manner. AR variants, induced by AR antagonism to mediate resistance to AR pathway inhibition, also enhance TNT production and rescue loss of clusterin- or YB-1-repressed TNT formation. TNT disruption sensitizes PCa to treatment-induced cell death. These data define a mechanistic network involving stress induction of chaperone and AR variants, PI3K/AKT signaling, actin remodeling and TNT-mediated intercellular communication that confer stress adaptative cell survival.