ipso-Substitution – A Novel Pathway for Microbial Metabolism of Endocrine-Disrupting 4-Nonylphenols, 4-Alkoxyphenols, and Bisphenol A

Our studies with Sphingobium xenophagum Bayram show that this bacterial strain degrades ?-quaternary 4-nonylphenols by an ipso-substitution mechanism, whereby the nonylphenol substrates are initially hydroxylated at the ipso position to form 4-hydroxy-4-nonylcyclohexa-2,5-dienones (quinols). Subsequently, the ?-quaternary side chains are able to detach as short-living cations from these intermediates. Alkyl branches attached to the carbocation help to delocalize and thereby stabilize the positive charge through inductive and hyperconjugative effects, which explains why only alkyl moieties of ?-quaternary nonylphenols are released. This view is corroborated by experiments with S. xenophagum Bayram, in which the alkyl chains of the non-?-quaternary 4-(1-methyloctyl) phenol (4-NP2) and 4-n-nonylphenol (4-NP1) were not released, so that the bacterium was unable to utilize these isomers as growth substrates. Analysis of dead end metabolites and experiments with 18O labeled H2O and O2 clearly show that in the main degradation pathway the nonyl cation derived from ?-quaternary quinols preferentially combines with a molecule of water to yield the corresponding alcohol and hydroquinone. However, the incorporation of significant amounts of O2-derived oxygen into the nonanol metabolites derived from degradation of certain ?,?-dimethyl substituted nonylphenols by strain Bayram strongly indicates the existence of a minor pathway in which the cation undergoes an alternative reaction and attacks the ipso-hydroxy group, yielding a 4-alkoxyphenol as an intermediate. Additional growth experiments with strain Bayram revealed that also the two alkoxyphenols 4-tert-butoxyphenol and 4-n-octyloxyphenol promote growth. Furthermore, strain Bayram's ipso-hydroxlating activity is able to transform also bisphenol A

Environmental Fate of Chiral Pollutants – the Necessity of Considering Stereochemistry

Many organic compounds regulated by environmental laws are chiral and are released into the environment as racemates. 3-Phenylbutanoic acid and mecoprop, two chiral pollutants, were enantioselectively degraded by pure cultures of microorganisms. This indicates the importance of assessing the environmental impact of stereoisomers separately, because selective enrichment of one of the enantiomers may occur in the environment. Field studies on the fate of highly polar, chiral compounds, like sulfophenylcarboxylates, are hampered by the lack of appropriate analytical methods for the separation of the enantiomers. Therefore, a method based on capillary electrophoresis with α-cyclodextrin as chiral selector was developed to separate the enantiomers of such compounds. In a field study at a Swiss waste disposal site, the fate of the chiral herbicide mecoprop was investigated. The enantiomeric ratio of (R)-mecoprop to (S)-mecoprop altered during groundwater passage of landfill leachate. This is a strong indication for in situ biodegradation. Our data imply that not only the enantiomers of a chiral drug or pesticide may exert different effects on the biological targets, but also their biodegradation and environmental fate may differ

Occurrence and temporal variations of TMDD in the river Rhine, Germany

Background, aim, and scope: The chemical substance 2,4,7,9-tetramethyl-5-decyne-4,7-diol (TMDD) is a non-ionic surfactant used as an industrial defoaming agent and in various other applications. Its commercial name is Surynol 104® and the related ethoxylates are also available as Surfynol® 420, 440, 465 and 485 which are characterized by different grades of ethoxylation of TMDD at both hydroxyl functional groups. TMDD and its ethoxylates offer several advantages in waterborne industrial applications in coatings, inks, adhesives as well as in paper industries. TMDD and its ethoxylates can be expected to reach the aquatic environment due its widespread use and its physico-chemical properties. TMDD has previously been detected in several rivers of Germany with concentrations up to 2.5 µg/L. In the United States, TMDD was also detected in drinking water. However, detailed studies about its presence and distribution in the aquatic environment have not been carried out so far. The aim of the present study was the analysis of the spatial and temporal concentration variations of TMDD in the river Rhine at the Rheingütestation Worms (443.3 km). Moreover, the transported load in the Rhine was investigated during two entire days and 7 weeks between November 2007 and January 2008. Materials and methods: The sampling was carried out at three different sampling points across the river. Sampling point MWL1 is located in the left part of the river, MWL2 in the middle part, and MWL4 in the right part. One more sampling site (MWL3) was run by the monitoring station until the end of 2006, but was put out of service due to financial constrains. The water at the left side of the river Rhine (MWL1) is influenced by sewage from a big chemical plant in Ludwigshafen and by the sewage water from this city. The water at the right side of the river Rhine (MWL4) is largely composed of the water inflow from river Neckar, discharging into Rhine 14.9 km upstream from the sampling point and of communal and industrial wastewater from the city Mannheim. The water from the middle of the river (MWL2) is largely composed of water from the upper Rhine. Water samples were collected in 1-L bottles by an automatic sampler. The water samples were concentrated by use of solid-phase extraction (SPE) using Bond Elut PPL cartridges and quantified by use of gas chromatography-mass spectrometry (GC-MS). The quantification was carried out with the internal standard method. Based on these results, concentration variations were determined for the day profiles and week profiles. The total number of analyzed samples was 219. Results: The results of this study provide information on the temporal concentration variability of TMDD in river Rhine in a cross section at one particular sampling point (443.3 km). TMDD was detected in all analyzed water samples at high concentrations. The mean concentrations during the 2 days were 314 ng/L in MWL1, 246 ng/L in MWL2, and 286 ng/L in MWL4. The variation of concentrations was low in the day profiles. In the week profiles, a trend of increasing TMDD concentrations was detected particularly in January 2008, when TMDD concentrations reached values up to 1,330 ng/L in MWL1. The mean TMDD concentrations during the week profiles were 540 ng/L in MWL1, 484 ng/L in MWL2, and 576 ng/L in MWL4. The loads of TMDD were also determined and revealed to be comparable in all three sections of the river. The chemical plant located at the left side of the Rhine is not contributing additional TMDD to the river. The load of TMDD has been determined to be 62.8 kg/d on average during the entire period. By extrapolation of data obtained from seven week profiles the annual load was calculated to 23 t/a. Discussion: The permanent high TMDD concentrations during the investigation period indicate an almost constant discharge of TMDD into the river. This observation argues for effluents of municipal wastewater treatment plants as the most likely source of TMDD in the river. Another possible source might be the degradation of ethoxylates of TMDD (Surfynol® series 400), in the WWTPs under formation of TMDD followed by discharge into the river. TMDD has to be considered as a high-production-volume (HPV) chemical based on the high concentrations found in this study. In the United States, TMDD is already in the list of HPV chemicals from the Environmental Protection Agency (EPA). However, the amount of TMDD production in Europe is unknown so far and also the biodegradation rates of TMDD in WWTPs have not been investigated. Conclusions: TMDD was found in high concentrations during the entire sampling period in the Rhine river at the three sampling points. During the sampling period, TMDD concentrations remained constant in each part of the river. These results show that TMDD is uniformly distributed in the water collected at three sampling points located across the river. ‘Waves’ of exceptionally high concentrations of TMDD could not be detected during the sampling period. These results indicate that the effluents of WWTPs have to be considered as the most important sources of TMDD in river Rhine. Recommendations and perspectives: Based also on the occurrence of TMDD in different surface waters of Germany with concentrations up to 2,500 ng/L and its presence in drinking water in the USA, more detailed investigations regarding its sources and distribution in the aquatic environment are required. Moreover, the knowledge with respect to its ecotoxicity and its biodegradation pathway is scarce and has to be gained in more detail. Further research is necessary to investigate the rate of elimination of TMDD in municipal and industrial wastewater treatment plants in order to clarify the degradation rate of TMDD and to determine to which extent effluents of WWTPs contribute to the input of TMDD into surface waters. Supplementary studies are needed to clarify whether the ethoxylates of TMDD (known as Surfynol 400® series) are hydrolyzed in the aquatic environment resulting in formation of TMDD similar to the well known cleavage of nonylphenol ethoxylates into nonylphenols. The stability of TMDD under anaerobic conditions in groundwater is also unknown and should be studied

Inheritance, Biochemical Abnormalities, and Clinical Features of Feline Mucolipidosis II: The First Animal Model of Human I-Cell Disease

Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73 times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage diseas

System performance of a prototype flatâ panel imager operated under mammographic conditions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135010/1/mp5051.pd

Functionality of Intergenic Transcription: An Evolutionary Comparison

Although a large proportion of human transcription occurs outside the boundaries of known genes, the functional significance of this transcription remains unknown. We have compared the expression patterns of known genes as well as intergenic transcripts within the ENCODE regions between humans and chimpanzees in brain, heart, testis, and lymphoblastoid cell lines. We find that intergenic transcripts show patterns of tissue-specific conservation of their expression, which are comparable to exonic transcripts of known genes. This suggests that intergenic transcripts are subject to functional constraints that restrict their rate of evolutionary change as well as putative positive selection to an extent comparable to that of classical protein-coding genes. In brain and testis, we find that part of this intergenic transcription is caused by widespread use of alternative promoters. Further, we find that about half of the expression differences between humans and chimpanzees are due to intergenic transcripts

APPFLx: Providing Privacy-Preserving Cross-Silo Federated Learning as a Service

Cross-silo privacy-preserving federated learning (PPFL) is a powerful tool to collaboratively train robust and generalized machine learning (ML) models without sharing sensitive (e.g., healthcare of financial) local data. To ease and accelerate the adoption of PPFL, we introduce APPFLx, a ready-to-use platform that provides privacy-preserving cross-silo federated learning as a service. APPFLx employs Globus authentication to allow users to easily and securely invite trustworthy collaborators for PPFL, implements several synchronous and asynchronous FL algorithms, streamlines the FL experiment launch process, and enables tracking and visualizing the life cycle of FL experiments, allowing domain experts and ML practitioners to easily orchestrate and evaluate cross-silo FL under one platform. APPFLx is available online at https://appflx.lin

Burden of postinfectious symptoms after acute Dengue, Vietnam.

We assessed predominantly pediatric patients in Vietnam with dengue and other febrile illness 3 months after acute illness. Among dengue patients, 47% reported >1 postacute symptom. Most resolved by 3 months, but alopecia and vision problems often persisted. Our findings provide additional evidence on postacute dengue burden and confirm children are affected

The preference for water nipples vs. water bowls in dairy goats

<p>Abstract</p> <p>Background</p> <p>Previous studies have reported that the design of the water dispensers can influence the water intake in farm animals. Horses and dairy cows seem to prefer to drink from an open surface whereas sheep and pigs apparently prefer water nipples, probably because of the worse water quality in water bowls. The aim of the present study was to examine the preference of dairy goats for water nipples or water bowls.</p> <p>Methods</p> <p>In each of the two experiments (exp. 1, dry goats, exp. 2 lactating goats), 42 dairy goats were allotted into 6 groups of 7 goats. In period 1, the goats had access to a water nipple. In period 2, they had access to a water bowl and in period 3 (preference test) they had access to both a water nipple and a water bowl. Water usage and wastage was recorded and water intake (water usage - water wastage) was calculated for each group for the two last days of each period. In experiment 2, water samples from each dispenser were analyzed for heterotrophy germs at 22°C, <it>Escherichia coli </it>and turbidity.</p> <p>Results</p> <p>Water usage was higher from water nipples than from water bowls both in experiment 1 (dry goats) and experiment 2 (lactating goats). There was however, no difference in water intake from water nipples and water bowls. In the preference test (period 3), the water intake tended to be higher from the water nipple than from the water bowl both for the dry goats (exp. 1) and lactating goats (exp. 2). Especially for the dry goats, the differences between groups were large. Turbidity and heterotrophy germs were much higher in the samples from the water bowls than from the water nipples.</p> <p>Water wastage from the water bowls was negligible compared to the water nipples. From the water nipples the water wastage was 30% and 23% of water usage for the dry and lactating goats respectively.</p> <p>Conclusions</p> <p>We conclude that type of water dispenser (nipple or bowl) was probably of minor importance for water intake in goats, but water bowls had a lower water quality.</p