Unraveling biogeochemical phosphorus dynamics in hyperarid Mars‐analogue soils using stable oxygen isotopes in phosphate

With annual precipitation less than 20 mm and extreme UV intensity, the Atacama Desert in northern Chile has long been utilized as an analogue for recent Mars. In these hyperarid environments, water and biomass are extremely limited, and thus, it becomes difficult to generate a full picture of biogeochemical phosphate‐water dynamics. To address this problem, we sampled soils from five Atacama study sites and conducted three main analyses—stable oxygen isotopes in phosphate, enzyme pathway predictions, and cell culture experiments. We found that high sedimentation rates decrease the relative size of the organic phosphorus pool, which appears to hinder extremophiles. Phosphoenzyme and pathway prediction analyses imply that inorganic pyrophosphatase is the most likely catalytic agent to cycle P in these environments, and this process will rapidly overtake other P utilization strategies. In these soils, the biogenic δ18O signatures of the soil phosphate (δ18OPO4) can slowly overprint lithogenic δ18OPO4 values over a timescale of tens to hundreds of millions of years when annual precipitation is more than 10 mm. The δ18OPO4 of calcium‐bound phosphate minerals seems to preserve the δ18O signature of the water used for biogeochemical P cycling, pointing toward sporadic rainfall and gypsum hydration water as key moisture sources. Where precipitation is less than 2 mm, biological cycling is restricted and bedrock δ18OPO4 values are preserved. This study demonstrates the utility of δ18OPO4 values as indicative of biogeochemical cycling and hydrodynamics in an extremely dry Mars‐analogue environment

The impact of mammalian target of rapamycin inhibition on bone health in postmenopausal women with hormone receptor-positive advanced breast cancer receiving everolimus plus exemestane in the phase IIIb 4EVER trial

Background: Breast cancer and its treatments are associated with a detrimental effect on bone health. Here we report the results of an exploratory analysis assessing changes in levels of biomarkers of bone metabolism in patients enrolled in the phase IIIb 4EVER study. Methods: The 4EVER trial investigated everolimus in combination with exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. In this prespecified exploratory analysis, changes in biomarkers of bone turnover were assessed in patients from baseline to weeks 4, 12, and 24. The serum bone markers assessed were procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25-OH-vitamin D). On-treatment changes in bone markers over time were described per subgroup of interest and efficacy outcomes. Results: Bone marker data were available for 241 of 299 enrolled patients. At the final assessment, P1NP, osteocalcin, PTH, 25-OH-vitamin D (all P < 0.001), and CTX (P = 0.036) were significantly decreased from baseline values per the Wilcoxon signed-rank test. At the last assessment (24 weeks or earlier), levels of serum CTX and PTH were significantly lower (P = 0.009 and P = 0.034, respectively) among patients with vs. without prior antiresorptive treatment (ART). Serum CTX levels were significantly lower (P < 0.001), and 25-OH-vitamin D concentrations significantly higher (P = 0.029), at the last postbaseline assessment in patients receiving concomitant ART vs. those without ART. Changes from baseline in PTH and 25-OH-vitamin D concentrations to the final assessment were significantly smaller in patients with prior ART. Lower baseline serum concentrations of osteocalcin and PTH were associated with clinical response (partial vs. non-response) at 24 weeks. High serum levels of CTX and P1NP at baseline were risk factors for progression at 12 weeks. Conclusions: These exploratory analyses support use of everolimus plus exemestane for the treatment of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer, and add to the body of evidence suggesting a potentially favorable impact of everolimus on bone turnover. Trial registration: NCT01626222. Registered 22 June 2012, https://clinicaltrials.gov/ct2/show/NCT01626222. Keywords: Bone health, Bone marker, Breast cancer, Everolimus, Hormone receptor-positive, Mammalian target of rapamyci