Carrier Detection of Ovine Hemophilia A Using an RFLP Marker, and Mapping of the Factor VIII Gene on the Ovine X-Chromosome

Ovine hemophilia A is an X-linked recessive bleeding disorder. For diagnostic purposes, restriction fragment length polymorphism (RFLP) analysis in the region of the factor VIII (F-VIII) gene was carried out using human F-VIII gene probes. The probe St14, Known to detect a highly polymorphic region that is closely linked to the F-VIII gene in humans, hybridized nonspecifcally with DNA from sheep. Searching for Intragenic RFLPs, the entire 9.0-kb coding sequence of the human F-VIII was used as a probe. Using the 1.8-kb Sstl/Kpnl F-VIII cDNA probe for hybridization, an Mspl-RFLP with allelic bands of 5.8 Kb (A1) and 4.2 kb (A2) was detected. A1 was in linkage phase with the mutated allele responsible for hemophilia A. The F-VIII locus in the sheep genome was assigned to the long arm of the X-chromosome in the region Xq24-q33, Using In situ hybridization with a 3-Kb human F-VIII cDNA probe to QFQ banded sheep metaphase chromosome

Determination of Hydrophilic and Amphiphilic Organic Pollutants in the Aquatic Environment

Environmental chemists performing monitoring or process-oriented fate and behavior studies on organic micropollutants face the challenge of having to determine low concentrations of problem compounds in complex mixtures and difficult matrices, such as sewage sludge, surface and groundwater. Selective extraction and enrichment help to overcome sensitivity limitations and also to reduce the number of different species in the sample. A subsequent chromatographic separation step, together with analyte-specific detection, finally allows to identify and quantify single analytes in the presence of other organic material. This article describes a selection of analytical development work carried out at EAWAG for the determination of hydrophilic and amphiphilic organic pollutants in the aquatic environment

An in vitro study on the toxic effects of nonylphenols (NP) in mitochondria

This paper is focused on alkylphenols, compounds which are formed by the biodegradation of polyethoxilatedalkylphenols detergents. Our experiments show that alkylphenols act not only as detergents, butalsoasuncouplersoftheoxidativephosphorylation. Thiseff~ot,canbeobservedatverylowdoses,thus suggesting that the preferential target ofnonylphenols in living organisms are mitochondria

Stress field sensitivity analysis in a sedimentary sequence of the Alpine foreland, Northern Switzerland

The stress field at depth is a relevant parameter for the design of subsurface constructions and reservoir management. Yet the distortion of the regional stress field due to local-scale features such as sedimentary and tectonic structures or topography is often poorly constrained. We conduct a stress sensitivity analysis using 3-D numerical geomechanical modelling with an elasto-plastic material law to explore the impact of such site specific features on the stress field in a sedimentary sequence of the Swiss Alpine foreland. The model\u27s dimensions are 14 km × 14 km × 3 km and it contains ten units with different mechanical properties, intersected by two regional fault zones. An initial stress state is established involving a semi-empirical relationship between the ratio of horizontal to vertical stress and the overconsolidation ratio of argillaceous sediments. The model results indicate that local topography can affect the stress field significantly to depths greater than the relief contrasts at the surface, especially in conjunction with horizontal tectonic loading. The complexity and frictional properties of faults are also relevant. The greatest variability of the stress field arises across the different sedimentary units. Stress magnitudes and stress anisotropy are much larger in stiffer formations such as massive limestones than in softer argillaceous formations. The stiffer formations essentially carry the load of the far-field forces and are therefore more sensitive to changes of the boundary conditions. This general characteristic of stress distribution in the stiff and soft formations is broadly maintained also with progressive loading towards the plastic limit. The stress field in argillaceous sediments within a stack of formations with strongly contrasting mechanical properties like in the Alpine foreland appears to be relatively insensitive to changes in the tectonic boundary conditions and is largely controlled by the maximum stiffness contrast with respect to the load-bearing formations

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

Smart homes and their users:a systematic analysis and key challenges

Published research on smart homes and their users is growing exponentially, yet a clear understanding of who these users are and how they might use smart home technologies is missing from a field being overwhelmingly pushed by technology developers. Through a systematic analysis of peer-reviewed literature on smart homes and their users, this paper takes stock of the dominant research themes and the linkages and disconnects between them. Key findings within each of nine themes are analysed, grouped into three: (1) views of the smart home-functional, instrumental, socio-technical; (2) users and the use of the smart home-prospective users, interactions and decisions, using technologies in the home; and (3) challenges for realising the smart home-hardware and software, design, domestication. These themes are integrated into an organising framework for future research that identifies the presence or absence of cross-cutting relationships between different understandings of smart homes and their users. The usefulness of the organising framework is illustrated in relation to two major concerns-privacy and control-that have been narrowly interpreted to date, precluding deeper insights and potential solutions. Future research on smart homes and their users can benefit by exploring and developing cross-cutting relationships between the research themes identified