A novel mutation in the sterol 27-hydroxylase gene of a woman with autosomal recessive cerebrotendinous xanthomatosis

<p>Article abstract</p> <p>Mutations of the gene encoding the mitochondrial enzyme sterol 27-hydroxylase (<it>CYP27A1 </it>gene) cause defects in the cholesterol pathway to bile acids that lead to the storage of cholestanol and cholesterol in tendons, lenses and the central nervous system. This disorder is the cause of a clinical syndrome known as cerebrotendinous xanthomatosis (CTX). Since 1991 several mutations of the <it>CYP27A1 </it>gene have been reported. We diagnosed the clinical features of CTX in a caucasian woman. Serum levels of cholestanol and 7α-hydroxycholesterol were elevated and the concentration of 27-hydroxycholesterol was reduced. Bile alcohols in the urine and faeces were increased. The analysis of the <it>CYP27A1 </it>gene showed that the patient was a compound heterozygote carrying two mutations both located in exon 8. One mutation is a novel four nucleotide deletion (c.1330-1333delTTCC) that results in a frameshift and the occurrence of a premature stop codon leading to the formation of a truncated protein of 448 amino acids. The other mutation, previously reported, is a C - > T transition (c. c.1381C > T) that converts the glutamine codon at position 461 into a termination codon (p.Q461X). These truncated proteins are expected to have no biological function being devoid of the cysteine residue at position 476 of the normal enzyme that is crucial for heme binding and enzyme activity.</p

Quantitative 1H NMR metabolomics reveals extensive metabolic reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures

<p>Abstract</p> <p>Background</p> <p>Opium poppy (<it>Papaver somniferum</it>) produces a diverse array of bioactive benzylisoquinoline alkaloids and has emerged as a model system to study plant alkaloid metabolism. The plant is cultivated as the only commercial source of the narcotic analgesics morphine and codeine, but also produces many other alkaloids including the antimicrobial agent sanguinarine. Modulations in plant secondary metabolism as a result of environmental perturbations are often associated with the altered regulation of other metabolic pathways. As a key component of our functional genomics platform for opium poppy we have used proton nuclear magnetic resonance (¹H NMR) metabolomics to investigate the interplay between primary and secondary metabolism in cultured opium poppy cells treated with a fungal elicitor.</p> <p>Results</p> <p>Metabolite fingerprinting and compound-specific profiling showed the extensive reprogramming of primary metabolic pathways in association with the induction of alkaloid biosynthesis in response to elicitor treatment. Using Chenomx NMR Suite v. 4.6, a software package capable of identifying and quantifying individual compounds based on their respective signature spectra, the levels of 42 diverse metabolites were monitored over a 100-hour time course in control and elicitor-treated opium poppy cell cultures. Overall, detectable and dynamic changes in the metabolome of elicitor-treated cells, especially in cellular pools of carbohydrates, organic acids and non-protein amino acids were detected within 5 hours after elicitor treatment. The metabolome of control cultures also showed substantial modulations 80 hours after the start of the time course, particularly in the levels of amino acids and phospholipid pathway intermediates. Specific flux modulations were detected throughout primary metabolism, including glycolysis, the tricarboxylic acid cycle, nitrogen assimilation, phospholipid/fatty acid synthesis and the shikimate pathway, all of which generate secondary metabolic precursors.</p> <p>Conclusion</p> <p>The response of cell cultures to elicitor treatment involves the extensive reprogramming of primary and secondary metabolism, and associated cofactor biosynthetic pathways. A high-resolution map of the extensive reprogramming of primary and secondary metabolism in elicitor-treated opium poppy cell cultures is provided.</p

Symmetries, Safety, and Self-Supervision

Collider searches face the challenge of defining a representation of high-dimensional data such that physical symmetries are manifest, the discriminating features are retained, and the choice of representation is new-physics agnostic. We introduce JetCLR to solve the mapping from low-level data to optimized observables though self-supervised contrastive learning. As an example, we construct a data representation for top and QCD jets using a permutation-invariant transformer-encoder network and visualize its symmetry properties. We compare the JetCLR representation with alternative representations using linear classifier tests and find it to work quite well

Charging of dielectric surfaces in contact with aqueous electrolyte -- the influence of CO2_2

The charge state of dielectric surfaces in aqueous environments is of fundamental and technological importance. We use super-heterodyne light scattering in a custom-made cell to study the influence of dissolved CO$_2$ on the charging of three, chemically different surfaces. We compare an ideal, CO$_2$-free reference state to ambient CO$_2$ conditions. Systems are conditioned under conductometric control at different low concentrations of NaCl. As expected for constant charge densities, zeta-potentials drop upon increasing the salt concentration in the reference state. Presence of CO$_2$ leads to an overall lowering of zeta-potentials. Moreover, for the inorganic dielectric, the salt dependent drop is significantly weakened, and it is inversed for the organic dielectrics. We suggest that at ambient conditions, the charge state of dielectric surfaces is related to dielectric charge regulation caused by the salt concentration dependent adsorption/desorption of CO$_2$.Comment: Thoroughly revised version, extended data, improved interpretation, Main text and supplementary materials, 23 Pages, 11 figures, submitted to Angew. Chem. Int E

The structure of the antimicrobial active center of lactoferricin B bound to sodium dodecyl sulfate micelles

AbstractLactoferricin B (LfcinB) is a 25-residue antimicrobial peptide released from bovine lactoferrin upon pepsin digestion. The antimicrobial center of LfcinB consists of six residues (RRWQWR-NH2), and it possesses similar bactericidal activity to LfcinB. The structure of the six-residue peptide bound to sodium dodecyl sulfate (SDS) micelles has been determined by NMR spectroscopy and molecular dynamics refinement. The peptide adopts a well defined amphipathic structure when bound to SDS micelles with the Trp sidechains separated from the Arg residues. Additional evidence demonstrates that the peptide is oriented in the micelle such that the Trp residues are more deeply buried in the micelle than the Arg and Gln residues

Biochar standardization and legislation harmonization

It is a relatively new concept to use biochar as soil amendment and for climate change mitigation. For this reason, the national and supranational legislation in the EU is not yet adequately prepared to regulate both the production and the application of biochar. Driven by this “regulatory gap”, voluntary biochar quality standards have been formed in Europe with the European Biochar Certificate, in the UK with the Biochar Quality Mandate and in the USA with the IBI Standard which is intended to be used internationally. In parallel to this, biochar producers and biochar users in a number of EU countries were partly successful in fitting the new biochar product into the existing national legislation for fertilisers, soil improvers and composts. The intended revision of the EC Regulation 2003/2003 on fertilisers offers the opportunity to regulate the use of biochar at the EU level. This publication summarizes the efforts on biochar standardization which have been carried out by voluntary products standards and illustrates existing legislation in EU member states, which apply to the production and use of biochar. It describes existing and planned EU regulations, which impact biochar applications and it develops recommendations on the harmonization of biochar legislation in the EU. &nbsp;First published online: 24 Jan 201

Turbulence Statistics Measurements in a Northern Hardwood Forest

Tower-based turbulence measurements were collected in and over a mixed hardwood forest at the University of Michigan BiologicalStation (UMBS) UMBS∼flux site in the northern summerof 2000. Velocity and temperature fluctuations were measured at five levels within the canopy (up to the canopy height, H = 21.4 m), using one- and three-dimensional sonic anemometers and fine-wire thermocouples. Six additional thermocouples were distributed over the canopy-layer depth. Three-dimensional velocities and sonic temperatures were also measured above the canopy at 1.6H and at 2.15H on the AmeriFlux tower located at the UMBS∼flux site. Vertical profiles of buoyancy flux, mean horizontal velocity, Reynolds stress, and standard deviation and skewness of velocity components were calculated. The analysis of these measurements aims at a multi-layer parameterization framework of turbulence statistics forimplementation in Lagrangian stochastic models. Turbulence profiles and power spectra above the canopy were analyzed in the context of Monin-Obukhov similarity theory (MOST) and Kolmogorov theory, as determined by stability at the top level (2.15H), to assess the extent to which surface scaling is valid as the canopy top is approached. Velocity spectra were computed to explore the potential of estimating the viscous dissipation rate, and results show that the high frequency range of the spectra above the canopy exhibits the roll-off predicted by Kolmogorov theory. Similarly, velocity standard deviations above the canopy converge to MOST predicted values toward the top level, and spectral peaks shift with stability, as expected. Within the canopy, both turbulence statistics profiles and spectral distributions follow the general known characteristics inside forests.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42505/1/10546_2004_Article_5117396.pd

SchussenAktivplus: reduction of micropollutants and of potentially pathogenic bacteria for further water quality improvement of the river Schussen, a tributary of Lake Constance, Germany

The project focuses on the efficiency of combined technologies to reduce the release of micropollutants and bacteria into surface waters via sewage treatment plants of different size and via stormwater overflow basins of different types. As a model river in a highly populated catchment area, the river Schussen and, as a control, the river Argen, two tributaries of Lake Constance, Southern Germany, are under investigation in this project. The efficiency of the different cleaning technologies is monitored by a wide range of exposure and effect analyses including chemical and microbiological techniques as well as effect studies ranging from molecules to communities