How microbial community composition, sorption and simultaneous application of six pharmaceuticals affect their dissipation in soils.

Pharmaceuticals may enter soils due to the application of treated wastewater or biosolids. Their leakage from soils towards the groundwater, and their uptake by plants is largely controlled by sorption and degradation of those compounds in soils. Standard laboratory batch degradation and sorption experiments were performed using soil samples obtained from the top horizons of seven different soil types and 6 pharmaceuticals (carbamazepine, irbesartan, fexofenadine, clindamycin and sulfamethoxazole), which were applied either as single-solute solutions or as mixtures (not for sorption). The highest dissipation half-lives were observed for citalopram (average DT50,S for a single compound of 152 ±â€¯53.5 days) followed by carbamazepine (106.0 ±â€¯17.5 days), irbesartan (24.4 ±â€¯3.5 days), fexofenadine (23.5 ±â€¯20.9 days), clindamycin (10.8 ±â€¯4.2 days) and sulfamethoxazole (9.6 ±â€¯2.0 days). The simultaneous application of all compounds increased the half-lives (DT50,M) of all compounds (particularly carbamazepine, citalopram, fexofenadine and irbesartan), which is likely explained by the negative impact of antibiotics (sulfamethoxazole and clindamycin) on soil microbial community. However, this trend was not consistent in all soils. In several cases, the DT50,S values were even higher than the DT50,M values. Principal component analyses showed that while knowledge of basic soil properties determines grouping of soils according sorption behavior, knowledge of the microbial community structure could be used to group soils according to the dissipation behavior of tested compounds in these soils. The derived multiple linear regression models for estimating dissipation half-lives (DT50,S) for citalopram, clindamycin, fexofenadine, irbesartan and sulfamethoxazole always included at least one microbial factor (either amount of phosphorus in microbial biomass or microbial biomarkers derived from phospholipid fatty acids) that deceased half-lives (i.e., enhanced dissipations). Equations for citalopram, clindamycin, fexofenadine and sulfamethoxazole included the Freundlich sorption coefficient, which likely increased half-lives (i.e., prolonged dissipations).

Competitive and synergic sorption of carbamazepine, citalopram, clindamycin, fexofenadine, irbesartan and sulfamethoxazole in seven soils.

Sorption of pharmaceuticals, which can occur in soils, may differ when present in a soil solution as a single compound or in a solution with other pharmaceuticals. Therefore, the sorption isotherms described by the Freundlich equations were evaluated for 6 compounds, which were applied in solutions of a single pharmaceutical, two pharmaceuticals or all pharmaceuticals to seven soils. Study mainly focused on a behavior of fexofenadine and irbesartan that occurred in soils in 3 forms (cationic, zwitter-ionic or neutral, anionic). Sorption of both compounds slightly increased (in some soils) when applied together, largely increased when applied with carbamazepine (neutral), and extremely increased when applied in solutions with citalopram (strongly sorbed cation), which could be explained by a cooperative multilayer sorption on soil constituents. On the other hand, sorption of both compounds moderately decreased when applied with clindamycin (cation and neutral) or sulfamethoxazole (neutral or anion). The magnitude of an increase or decrease in the Freundlich sorption coefficient (KF) for a particular compound depended on soil conditions, a form of compound's molecule and its interaction with molecules of other compounds. Despite sorption being influenced by other compound(s) in solution, the KF coefficients evaluated for a particular compound under the different conditions were mostly correlated with the same soil properties: KF,CAR with an organic carbon content, KF,CIT and KF,CLI with a base cation saturation, KF,SUL with hydrolytic acidity, and KF,FEX and KF,IRB with sorption complex saturation.

A complex role for FGF-2 in self-renewal, survival, and adhesion of human embryonic stem cells.

The transcription program that is responsible for the pluripotency of human ESCs (hESCs) is believed to be comaintained by exogenous fibroblast growth factor-2 (FGF-2), which activates FGF receptors (FGFRs) and stimulates the mitogen-activated protein kinase (MAPK) pathway. However, the same pathway is stimulated by insulin receptors, insulin-like growth factor 1 receptors, and epidermal growth factor receptors. This mechanism is further complicated by intracrine FGF signals. Thus, the molecular mechanisms by which FGF-2 promotes the undifferentiated growth of hESCs are unclear. Here we show that, in undifferentiated hESCs, exogenous FGF-2 stimulated the expression of stem cell genes while suppressing cell death and apoptosis genes. Inhibition of autocrine FGF signaling caused upregulation of differentiation-related genes and downregulation of stem cell genes. Thus, exogenous FGF-2 reinforced the pluripotency maintenance program of intracrine FGF-2 signaling. Consistent with this hypothesis, expression of endogenous FGF-2 decreased during hESC differentiation and FGF-2 knockdown-induced hESC differentiation. In addition, FGF-2 signaling via FGFR2 activated MAPK kinase/extracellular signal-regulated kinase and AKT kinases, protected hESC from stress-induced cell death, and increased hESC adhesion and cloning efficiency. This stimulation of self-renewal, cell survival, and adhesion by exogenous and endogenous FGF-2 may synergize to maintain the undifferentiated growth of hESCs.