In this study, quantitative and qualitative changes in antibiotics resistance genes (ARGs) were investigated in two municipal wastewater treatment plants (WWTPs) treating pretreated livestock or ...industrial wastewater as well as municipal sewage. Total eight ARGs (tetX, tetM, tetA, sul1, sul2, ermB, qnrD, and blaTEM) were quantified, and their relative abundance was assessed by ARGs copies/16S rRNA gene copies. The fate of ARGs was observed to be different between two WWTPs: sul, qnrD, and blaTEM were proliferated during the treatment processes only in the WWTP1 which received pretreated livestock wastewater. Furthermore, dynamic shifts in patterns of ARGs occurrence were observed during biological, secondary sedimentation and coagulation processes. During biological treatment in both WWTPs, relative abundance of tet and ermB changed: tet increased significantly by 211.6–357.6%, while ermB decreased by 70.4–92.0%. Little variation was observed in sul, qnrD and blaTEM. Subsequently, the relative abundance of tet decreased during the secondary sedimentation and coagulation in both WWTPs: tet decreased by 56.0–86.3% during sedimentation and by 48.2–75.7% during coagulation, respectively. During the final treatment, different responses of antibiotic resistance bacteria (ARB) and ARGs to ultraviolet (UV) disinfection were found: removal efficiencies of ARB were observed in the range of 34–75%, while obvious reduction in ARGs was not observed at the UV dose of 27mJ/cm2. Although ARGs underwent various treatment processes, considerable levels of ARGs remained at discharge amounting to 4.2×1018 copies/day from WWTP1 and 5.4×1016 copies/day from WWTP2, respectively.
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•Quantitative and qualitative changes in ARGs were investigated in WWTPs.•Changes were unique for each ARG community while undergoing treatment processes.•Variation in ARGs was largest during biological and post-physiochemical processes.•ARGs showed limited response to UV disinfection.•ARB were reduced by UV disinfection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Bisphenol A (BPA) exposure during the perinatal and postnatal periods increases the susceptibility to disease over the life cycle. However, information on the BPA delivered to fetuses or infants via ...the placenta and breastfeeding is limited. We determined the BPA exposure levels in various bodily fluids and tissues of pregnant women and described fetus and infant exposures to BPA based on associations and BPA ratios in mother–neonate paired samples. Maternal serum, urine, placenta, breast milk, cord serum, and neonatal urine samples were collected from 318 mother–neonate pairs at six university hospitals in Korea. BPA levels were detected using liquid chromatography tandem mass spectrometry. The ratios of the BPA levels in the other sample types to the levels in maternal serum were calculated. BPA was detected in 79.5–100% of the maternal and fetal samples. The median BPA concentration in the samples decreased in the order of neonatal urine (4.75ng/mL), maternal urine (2.86ng/mL), cord serum (1.71ng/mL), maternal serum (1.56ng/mL), breast milk (0.74ng/mL), and the placenta (0.53ng/g). We estimated the ratios of BPA levels in the other sample types to those in maternal serum. The median (95th percentile) cord serum-to-maternal serum ratio was 1.12 (15.2) for 160 mother–fetal pairs, in which BPA was detected in both samples. The placenta-, maternal urine-, neonatal urine-, and breast milk-to-maternal serum ratios were 0.28 (5.31), 1.79 (29.9), 1.98 (28.2), and 0.51 (10.5), respectively. In addition, the median (95th percentile) cord serum-to-placenta ratio was 4.03 (45.8), and the neonatal urine-to-cord serum ratio was 1.95 (25.6). The 95th percentile values were 14–20-fold greater than the medians. Urine contained the highest BPA concentrations, followed by serum, breast milk, and the placenta. The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.
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•Not enough data on tissue distribution of BPA in mother‑neonate (or fetus) pair•The order of BPA concentrations in examined tissue or bio-samples are urine in mother and neonates>cord serum>maternal serum>breast milk>placenta.•BPA in cord serum, significantly associated with in maternal serum and urine but not in others.•The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Parabens are commonly used as antimicrobial preservatives in consumer products. Because of their possible endocrine-disrupting activities, their safety has become a public concern. Although ...pharmacokinetic studies on parabens have been conducted in animals, limited information exists on their pharmacokinetic profiles in humans. In the present study, we determined the pharmacokinetic characteristics of propyl paraben (PP) in humans following a single oral administration of 0.6 mg/kg bw of deuterium labeled-PP. We also conducted experiment with similar design but different exposure amount (2.5 mg/kg bw) to verify the validity of the model to be developed. Blood and urine were collected at several intervals over the course of 48 h to measure levels of PP and its metabolites (conjugates and hydrolysates) in 12 male volunteers. The unconjugated parent compound (free PP), glucuronide and sulfate conjugates, p-hydroxybenzoic acid, and p-hydroxyhippuric acid were measured using HPLC-MS/MS. It was found that PP was rapidly absorbed via ingestion within 2 h and quickly eliminated (terminal half-life, 2.9 h). The fraction of administered dose excreted in the urine was 0.05% for free PP, 8.6% for total PP (free + conjugates), 23.2% for p-hydroxyhippuric acid, and 7.0% for p-hydroxybenzoic acid. Utilizing this pharmacokinetic profile, we successfully constructed a multi-compartment model where the disposition of PP was well described with two compartments and that of its metabolites was explained with first-order reactions. The present pharmacokinetic model provides insights into the kinetic properties of the disposition of PP and its metabolites in humans, and it can be used for risk assessment with biomonitoring of PP.
•Pharmacokinetic of propyl paraben following oral administration was investigated for the first time in humans.•The unconjugated propyl paraben in urine is below 0.1% of the administered propyl paraben.•The urinary excretion factor for propyl paraben is 8.6 ± 1.4%.•The ADME for propyl paraben was well described by a two-compartment model.•Propyl paraben is rapidly absorbed (<2 h) and completely eliminated from the body.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Long-term propionate enrichment to develop high strength syntrophic consortia.•Syntrophaceae were most dominant group to degrade propionate.•Syntrophomonadaceae group degraded ...butyrate produced from propionate oxidation.•pH 6.8–6.9 and temperature 34.5–34.9 °C were found to be optimum growth conditions.•No two-way interaction between pH and temperature was found from ANOVA.
Propionate is a quantitatively important methanogenic intermediate in anaerobic digesters and only limited number of microbes can utilize it under syntrophic association with methanogens. The syntrophic propionate oxidizing bacterias are known to be slow growers due to the low energy yield. Thus, propionate get accumulated frequently in anaerobic digesters and it negatively affect digester performance. In this study, propionate degrading consortia from four different seeding sources were enriched in sequential bath mode in two phases; first adaption phase with 1 g/L of propionate concentration and later, high-strength phase with 3 g/L. From 16s rRNA gene based metagenomics analysis of the former phase, four syntrophic microbial groups, Syntrophaceae, Syntrophomonadaceae, Methanobacterium and Methanosaeta were found to be dominant with complete degradation of propionate. The substrate accelerated microbial shifts were observed at high-strength phase with significant decrease of Syntrophaceae up to 26.9 %. Using Response Surface Methodology, pH 6.8–6.9 and temperature 34.5–34.9 °C were found to be optimum growth conditions for the propionate degradation culture. Observed results could be useful to improve degradation efficiencies and obtained enriched culture can be used to recover propionate-accumulated digesters by bio-augmentation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The digit tips of children and rodents are known to regenerate following amputation. The skeletal structure that regenerates is the distal region of the terminal phalangeal bone that is associated ...with the nail organ. The terminal phalanx forms late in gestation by endochondral ossification and continues to elongate until sexual maturity (8 weeks of age). Postnatal elongation at its distal end occurs by appositional ossification, i.e. direct ossification on the surface of the terminal phalanx, whereas proximal elongation results from an endochondral growth plate. Amputation through the middle of the terminal phalanx regenerates whereas regenerative failure is observed following amputation to remove the distal 2/3 of the bone. Regeneration is characterized by the formation of a blastema of proliferating cells that appear undifferentiated and express
Bmp4. Using chondrogenic and osteogenic markers we show that redifferentiation does not occur by endochondral ossification but by the direct ossification of blastema cells that form the rudiment of the digit tip. Once formed the rudiment elongates by appositional ossification in parallel with unamputated control digits. Regenerated digits are consistently shorter than unamputated control digits. Finally, we present a case study of a child who suffered an amputation injury at a proximal level of the terminal phalanx, but failed to regenerate despite conservative treatment and the presence of the nail organ. These clinical and experimental findings expand on previously published observations and initiate a molecular assessment of a mammalian regeneration model.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The MgtC virulence protein from the intracellular pathogen Salmonella enterica is required for its intramacrophage survival and virulence in mice and this requirement of MgtC is conserved in several ...intracellular pathogens including Mycobacterium tuberculosis. Despite its critical role in survival within macrophages, only a few molecular targets of the MgtC protein have been identified. Here, we report that MgtC targets PhoR histidine kinase and activates phosphate transport independently of the available phosphate concentration. A single amino acid substitution in PhoR prevents its binding to MgtC, thus abrogating MgtC-mediated phosphate transport. Surprisingly, the removal of MgtC's effect on the ability to transport phosphate renders Salmonella hypervirulent and decreases a non-replicating population inside macrophages, indicating that MgtC-mediated phosphate transport is required for normal Salmonella pathogenesis. This provides an example of a virulence protein directly activating a pathogen's phosphate transport inside host.
Bone morphogenetic proteins (BMPs) are required for bone development, the repair of damage skeletal tissue, and the regeneration of the mouse digit tip. Previously we showed that BMP treatment can ...induce a regeneration response in mouse digits amputated at a proximal level of the terminal phalangeal element (P3) (Yu et al., 2010). In this study, we show that the regeneration-inductive ability of BMP2 extends to amputations at the level of the second phalangeal element (P2) of neonatal digits, and the hindlimb of adult limbs. In these models the induced regenerative response is restricted in a segment-specific manner, thus amputated skeletal elements regenerate distally patterned skeletal structures but does not form joints or more distal skeletal elements. Studies on P2 amputations indicate that BMP2-induced regeneration is associated with a localized proliferative response and the transient expression of established digit blastema marker genes. This is followed by the formation of a new endochondral ossification center at the distal end of the bone stump. The endochondral ossification center contains proliferating chondrocytes that establish a distal proliferative zone and differentiate proximally into hypertrophic chondrocytes. Skeletal regeneration occurs from proximal to distal with the appearance of osteoblasts that differentiate in continuity with the amputated stump. Using the polarity of the endochondral ossification centers induced by BMP2 at two different amputation levels, we show that BMP2 activates a level-dependent regenerative response indicative of a positional information network. In summary, our studies provide evidence that BMP2 induces the regeneration of mammalian limb structures by stimulating a new endochondral ossification center that utilizes an existing network of positional information to regulate patterning during skeletal regeneration.
► Following amputation in mice BMP2 induces a skeletal regenerative response. ► BMP2 stimulated cell proliferation and an endochondral ossification center forms. ► A distal growth plate like structure organizes the direction of skeletal outgrowth. ► BMP2 induced regeneration is specific to the level of amputation. ► BMP2 is a critical factor for successful limb regeneration in mammals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Paclitaxel is commonly used as a second-line therapy for advanced gastric cancer (AGC). The decision to proceed with second-line chemotherapy and select an appropriate regimen is critical for ...vulnerable patients with AGC progressing after first-line chemotherapy. However, no predictive biomarkers exist to identify patients with AGC who would benefit from paclitaxel-based chemotherapy.
This study included 288 patients with AGC receiving second-line paclitaxel-based chemotherapy between 2017 and 2022 as part of the K-MASTER project, a nationwide government-funded precision medicine initiative. The data included clinical (age young-onset vs. others, sex, histology intestinal vs. diffuse type, prior trastuzumab use, duration of first-line chemotherapy), and genomic factors (pathogenic or likely pathogenic variants). Data were randomly divided into training and validation sets (0.8:0.2). Four machine learning (ML) methods, namely random forest (RF), logistic regression (LR), artificial neural network (ANN), and ANN with genetic embedding (ANN with GE), were used to develop the prediction model and validated in the validation sets.
The median patient age was 64 years (range 25-91), and 65.6% of those were male. A total of 288 patients were divided into the training (n = 230) and validation (n = 58) sets. No significant differences existed in baseline characteristics between the training and validation sets. In the training set, the areas under the ROC curves (AUROC) for predicting better progression-free survival (PFS) with paclitaxel-based chemotherapy were 0.499, 0.679, 0.618, and 0.732 in the RF, LR, ANN, and ANN with GE models, respectively. The ANN with the GE model that achieved the highest AUROC recorded accuracy, sensitivity, specificity, and F1-score performance of 0.458, 0.912, 0.724, and 0.579, respectively. In the validation set, the ANN with GE model predicted that paclitaxel-sensitive patients had significantly longer PFS (median PFS 7.59 vs. 2.07 months, P = 0.020) and overall survival (OS) (median OS 14.70 vs. 7.50 months, P = 0.008). The LR model predicted that paclitaxel-sensitive patients showed a trend for longer PFS (median PFS 6.48 vs. 2.33 months, P = 0.078) and OS (median OS 12.20 vs. 8.61 months, P = 0.099).
These ML models, integrated with clinical and genomic factors, offer the possibility to help identify patients with AGC who may benefit from paclitaxel chemotherapy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The regenerating digit tip of mice is a novel epimorphic response in mammals that is similar to fingertip regeneration in humans. Both display restricted regenerative capabilities that are ...amputation-level dependent. Using this endogenous regeneration model in neonatal mice, we have found that noggin treatment inhibits regeneration, thus suggesting a bone morphogenetic protein (BMP) requirement. Using non-regenerating amputation wounds, we show that BMP7 or BMP2 can induce a regenerative response. BMP-induced regeneration involves the formation of a mammalian digit blastema. Unlike the endogenous regeneration response that involves redifferentiation by direct ossification (evolved regeneration), the BMP-induced response involves endochondral ossification (redevelopment). Our evidence suggests that BMP treatment triggers a reprogramming event that re-initiates digit tip development at the amputation wound. These studies demonstrate for the first time that the postnatal mammalian digit has latent regenerative capabilities that can be induced by growth factor treatment.
In this study, the characteristics of automated emergency brake (AEB) systems in rear-end collision situations and cut-in situations is presented. Accident scenarios to reproduce the collision ...situations are suggested by data analysis of traffic accident databases. Two test vehicles are selected to compare the performance of the AEB systems. The operation method of the AEB systems differs depending on the automobile manufacturer. In the test cases of rear-end collision, the test vehicle ‘A’ applies braking before 0.91 s before collision, which leads no collision in all test cases. The other test vehicle ‘B’ showed non-severe three collisions out of six test cases in rear-end collision tests. The relative speed of the collisions is less than 18kph, which would make no severe damage on the driver and the vehicle itself. In the case of cut-in collision situations, the test vehicle ‘A’ showed three collisions out of six cut-in experiments. In the one of the collision cases, the maximum relative speed at the collision was 38.5 kph, which can cause severe damage. The test vehicle ‘B’ showed collisions in five cases out of six test cases. The relative speed at the collisions was less than 18 kph, which is the same performance as the rear-end collision cases.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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