Mammalian CDC14 phosphatases control exit from stemness in pluripotent cells.

Maintenance of stemness is tightly linked to cell cycle regulation through protein phosphorylation by cyclin-dependent kinases (CDKs). However, how this process is reversed during differentiation is unknown. We report here that exit from stemness and differentiation of pluripotent cells along the neural lineage are controlled by CDC14, a CDK-counteracting phosphatase whose function in mammals remains obscure. Lack of the two CDC14 family members, CDC14A and CDC14B, results in deficient development of the neural system in the mouse and impairs neural differentiation from embryonic stem cells (ESCs). Mechanistically, CDC14 directly dephosphorylates specific proline-directed Ser/Thr residues of undifferentiated embryonic transcription Factor 1 (UTF1) during the exit from stemness, triggering its proteasome-dependent degradation. Multiomic single-cell analysis of transcription and chromatin accessibility in differentiating ESCs suggests that increased UTF1 levels in the absence of CDC14 prevent the proper firing of bivalent promoters required for differentiation. CDC14 phosphatases are dispensable for mitotic exit, suggesting that CDC14 phosphatases have evolved to control stemness rather than cell cycle exit and establish the CDK-CDC14 axis as a critical molecular switch for linking cell cycle regulation and self-renewal.

Climate-induced changes in continental-scale soil macroporosity may intensify water cycle.

Soil macroporosity affects field-scale water-cycle processes, such as infiltration, nutrient transport and runoff1,2, that are important for the development of successful global strategies that address challenges of food security, water scarcity, human health and loss of biodiversity3. Macropores-large pores that freely drain water under the influence of gravity-often represent less than 1 per cent of the soil volume, but can contribute more than 70 per cent of the total soil water infiltration4, which greatly magnifies their influence on the regional and global water cycle. Although climate influences the development of macropores through soil-forming processes, the extent and rate of such development and its effect on the water cycle are currently unknown. Here we show that drier climates induce the formation of greater soil macroporosity than do more humid ones, and that such climate-induced changes occur over shorter timescales than have previously been considered-probably years to decades. Furthermore, we find that changes in the effective porosity, a proxy for macroporosity, predicted from mean annual precipitation at the end of the century would result in changes in saturated soil hydraulic conductivity ranging from -55 to 34 per cent for five physiographic regions in the USA. Our results indicate that soil macroporosity may be altered rapidly in response to climate change and that associated continental-scale changes in soil hydraulic properties may set up unexplored feedbacks between climate and the land surface and thus intensify the water cycle.

Forecasting leachate generation from pilot woodchip stockpiles using a three-dimensional transient flow model.

Leachate generation from open stockpiles of recycled woodchip materials is potentially harmful to aquatic ecosystems. There is growing interest in using numerical models to simulate leachate generation from outdoor piles, but this requires information about the hydraulic properties of the materials. The objectives of this study were to simulate leachate from woodchip piles with the numerical model HYDRUS-3D and to optimize subsets of parameters for single (SPM) and dual (DPM) pore flow models with the Bayesian Markov Chain Monte Carlo algorithm DREAMZS. Three experimental piles, each approximately 30 m3, were setup with mixtures of either once (coarse) or twice (fine) ground woodchips. Leachate continuously collected over a period of six months was similar across piles. As a result, subsets of optimized flow parameters for the coarse and fine woodchips were not different. Leachate predictions by the two pore flow models were similar and agreed reasonably with the field measurements, as indicated by Nash-Sutcliffe efficiency values greater than 0.6. This result suggests the simpler SPM is adequate for field predictions of leachate. However, leachate was consistently under-predicted by both pore models by 13-27% during rainfall events with more than 1 cm in 6 h. The optimized flow models can be used as a tool for studying pile management strategies.

Nitrogen-mediated effects of elevated CO2 on intra-aggregate soil pore structure.

Soil pore structure has a strong influence on water retention, and is itself influenced by plant and microbial dynamics such as root proliferation and microbial exudation. Although increased nitrogen (N) availability and elevated atmospheric CO2 concentrations (eCO2 ) often have interacting effects on root and microbial dynamics, it is unclear whether these biotic effects can translate into altered soil pore structure and water retention. This study was based on a long-term experiment (7 yr at the time of sampling) in which a C4 pasture grass (Paspalum notatum) was grown on a sandy loam soil while provided factorial additions of N and CO2 . Through an analysis of soil aggregate fractal properties supported by 3D microtomographic imagery, we found that N fertilization induced an increase in intra-aggregate porosity and a simultaneous shift toward greater accumulation of pore space in larger aggregates. These effects were enhanced by eCO2 and yielded an increase in water retention at pressure potentials near the wilting point of plants. However, eCO2 alone induced changes in the opposite direction, with larger aggregates containing less pore space than under control conditions, and water retention decreasing accordingly. Results on biotic factors further suggested that organic matter gains or losses induced the observed structural changes. Based on our results, we postulate that the pore structure of many mineral soils could undergo N-dependent changes as atmospheric CO2 concentrations rise, having global-scale implications for water balance, carbon storage, and related rhizosphere functions.

Characterization of wood mulch and leachate/runoff from three wood recycling facilities.

Large-scale open storage of wood mulch is common practice at wood recycling facilities. During rain and snow melt, leachate with soluble compounds and suspended particles is released from mulch stockpiles. The objective of this study was to determine the quality of leachate/runoff from wood recycling facilities to evaluate its potential to contaminate receiving waterbodies. Wood mulch (n = 30) and leachate/runoff (n = 26) samples were collected over 1.5 years from three wood recycling facilities in New Jersey, USA. Differences by site were found (p < 0.05) for most of the 21 constituents tested in the solid wood mulch samples. Biochemical oxygen demand (range <20-3000 mg/L), chemical oxygen demand (134-6000 mg/L) and total suspended solids (69-401 mg/L) median concentrations of the leachate/runoff samples were comparable to those of untreated domestic wastewater. Total Kjeldahl N, total P and fecal coliform median values were slightly lower than typical wastewater values. Dose-response studies with leachate/runoff samples using zebrafish (Danio rerio) embryos showed that mortality and developmental defects typically did not occur even at the highest concentration tested, indicating low toxicity, although delayed development did occur. Based on this study, leachate/runoff from wood recycling facilities should not be released to surface waters as it is a potential source of organic contamination and low levels of nutrients. A study in which runoff from a controlled drainage area containing wood mulch of known properties is monitored would allow for better assessment of the potential impact of stormwater runoff from wood recycling facilities.

Decadal-scale shifts in soil hydraulic properties as induced by altered precipitation.

Soil hydraulic properties influence the partitioning of rainfall into infiltration versus runoff, determine plant-available water, and constrain evapotranspiration. Although rapid changes in soil hydraulic properties from direct human disturbance are well documented, climate change may also induce such shifts on decadal time scales. Using soils from a 25-year precipitation manipulation experiment, we found that a 35% increase in water inputs substantially reduced infiltration rates and modestly increased water retention. We posit that these shifts were catalyzed by greater pore blockage by plant roots and reduced shrink-swell cycles. Given that precipitation regimes are expected to change at accelerating rates globally, shifts in soil structure could occur over broad regions more rapidly than expected and thus alter water storage and movement in numerous terrestrial ecosystems.

Persistence of acetochlor, atrazine, and S-metolachlor in surface and subsurface horizons of 2 typic argiudolls under no-tillage.

Variations in soil properties with depth strongly influence the degradation and persistence of herbicides, underlining the importance of studying these processes in soil horizons with distinctively different properties. The persistence of the herbicides acetochlor, atrazine, and S-metolachlor was measured in samples of the A, B, and C horizons of 2 Typic Argiudolls from Argentina under no-till management. The soils studied differed in soil organic carbon (OC) content, pH, particle size distribution, and structure. Quantification of herbicides in soil was done through high-performance liquid chromatography with diode array detector. There were interactions of herbicide × horizon (p < 0.01) that resulted in degradation rates (k) of all herbicides decreasing, and their corresponding dissipation half-life (DT50) values increasing, with soil depth. Herbicide persistence across all soils and horizons ranged from 15 to 73 d for acetochlor, 13 to 29 d for atrazine, and 82 to 141 d for S-metolachlor, which had significantly (p < 0.01) greater persistence than atrazine and acetochlor. The DT50 values of herbicides were negatively correlated with the contents of OC (correlation coefficients ranging from -0.496 to -0.773), phosphorus (-0.427 to -0.564), and nitrogen-nitrate (-0.507 to -0.662), and with microbial activity (-0.454 to -0.687) and the adsorption coefficient (-0.530 to -0.595); DT50s were positively correlated with pH (0.366 to 0.648). Adsorption was likely the most influential process in determining persistence of these herbicides in surface and subsurface horizons. The present study can potentially improve the prediction of the fate of acetochlor, atrazine, and S-metolachlor in soils because it includes much needed information on the degradation of the herbicides in subsurface horizons. Environ Toxicol Chem 2017;36:3065-3073. © 2017 SETAC.

Sorption of acetochlor, S-metolachlor, and atrazine in surface and subsurface soil horizons of Argentina.

Understanding herbicide sorption within soil profiles is the first step to predicting their behavior and leaching potential. Laboratory studies were conducted to determine the influence of surface and subsurface soil properties on acetochlor, atrazine, and S-metolachlor sorption. Soil samples were taken from horizons A, B, and C of two loamy soils of the humid pampas of Argentina under no-till management; horizon A was divided into two layers, A(0) (0-5 cm) and A(1) (5 cm to the full thickness of an A horizon). Sorption isotherms were determined from each sampled horizon using the batch equilibrium method and seven concentrations (0, 0.1, 0.5, 2.0, 5.0, 10.0, and 20.0 mg L(-1)). Sorption affinity of herbicides was approximated by the Freundlich equation. The sorption strength K(f) (mg(1 - 1/n) kg(-1) L(1/n) ) over the soils and horizons studied followed the order S-metolachlor (16.51-29.19) > atrazine (4.85-12.34) ≥ acetochlor (5.17-11.97), which was closely related to the hydrophobicity of herbicides expressed as octanol-water partition coefficient (K(OW) ). The K(f) values of the three herbicides were positively correlated with soil organic carbon, with a significance of p < 0.01. Values of K(f) for the three herbicides decreased with depth in the two soils, indicating greater sorption onto surficial soil horizons and possibly a delayed transport toward subsurface soils and subsequent pollution of groundwater.

Hormone replacement therapy and the risk of breast cancer: assessment of therapy acceptance in a cohort of previously treated breast cancer patients.

INTRODUCTION: In the postmenopausal period, an average of 25% of women will present symptomatic ovarian failure requiring hormonal replacement therapy. Estrogen can relieve vasomotor symptoms. Hormonal replacement therapy is generally not recommended for breast cancer patients due to the potential risk of tumor recurrence. To answer the questions about the safety of hormonal replacement therapy in this subgroup of women, it is necessary to establish the acceptance of treatment. METHODS: Between September 1998 and February 2001, a cohort of 216 breast cancer patients were asked to complete a questionnaire. All patients had completed their treatment and were informed about survival rates after breast cancer and hormonal replacement therapy. RESULTS: Among the 216 patients, 134 (62%) would refuse hormonal replacement therapy. A hundred patients were afraid of relapse (74.6%). Adjuvant tamoxifen therapy was the only statistically significant variable (70.3% versus 29.7% p=0.003). Understanding clinical stage (p= 0.045) and type of medical assistance (private versus public, p=0.033) also seemed to influence the decision. Early stage disease (p= 0.22), type of surgical procedure (radical versus conservative, p=0.67), adjuvant chemotherapy (p=0.082) or marital status (p=0.98 ) were not statistically significant in decision making. Several patients submitted to adjuvant chemotherapy (41.6%) would accept hormonal replacement therapy under medical supervision, as did most of advanced clinical stage patients (58.3%; p=0.022). CONCLUSION: There is a high level of rejection for hormonal replacement therapy among breast cancer patients when current data on tumor cure rates, and potential risks of estrogen use is available. Adverse effects of tamoxifen in the adjuvant setting may be the reason for refusal of hormonal replacement therapy.

Hormone replacement therapy and the risk of breast cancer: assessment of therapy acceptance in a cohort of previously treated breast cancer patients

INTRODUCTION: In the postmenopausal period, an average of 25 percent of women will present symptomatic ovarian failure requiring hormonal replacement therapy. Estrogen can relieve vasomotor symptoms. Hormonal replacement therapy is generally not recommended for breast cancer patients due to the potential risk of tumor recurrence. To answer the questions about the safety of hormonal replacement therapy in this subgroup of women, it is necessary to establish the acceptance of treatment. METHODS: Between September 1998 and February 2001, a cohort of 216 breast cancer patients were asked to complete a questionnaire. All patients had completed their treatment and were informed about survival rates after breast cancer and hormonal replacement therapy. RESULTS: Among the 216 patients, 134 (62 percent) would refuse hormonal replacement therapy. A hundred patients were afraid of relapse (74.6 percent). Adjuvant tamoxifen therapy was the only statistically significant variable (70.3 percent versus 29.7 percent p=0.003). Understanding clinical stage (p= 0.045) and type of medical assistance (private versus public , p=0.033) also seemed to influence the decision. Early stage disease (p= 0.22), type of surgical procedure (radical versus conservative, p=0.67), adjuvant chemotherapy (p=0.082) or marital status (p=0.98 ) were not statistically significant in decision making. Several patients submitted to adjuvant chemotherapy (41.6 percent) would accept hormonal replacement therapy under medical supervision, as did most of advanced clinical stage patients (58.3 percent; p=0.022). CONCLUSION: There is a high level of rejection for hormonal replacement therapy among breast cancer patients when current data on tumor cure rates, and potential risks of estrogen use is available. Adverse effects of tamoxifen in the adjuvant setting may be the reason for refusal of hormonal replacement therapy