Majorana spinors and extended Lorentz symmetry in four-dimensional theory

An extended local Lorentz symmetry in four-dimensional (4D) theory is considered. A source of this symmetry is a group of general linear transformations of four-component Majorana spinors GL(4,M) which is isomorphic to GL(4,R) and is the covering of an extended Lorentz group in a 6D Minkowski space M(3,3) including superluminal and scaling transformations. Physical space-time is assumed to be a 4D pseudo-Riemannian manifold. To connect the extended Lorentz symmetry in the M(3,3) space with the physical space-time, a fiber bundle over the 4D manifold is introduced with M(3,3) as a typical fiber. The action is constructed which is invariant with respect to both general 4D coordinate and local GL(4,M) spinor transformations. The components of the metric on the 6D fiber are expressed in terms of the 4D pseudo-Riemannian metric and two extra complex fields: 4D vector and scalar ones. These extra fields describe in the general case massive particles interacting with an extra U(1) gauge field and weakly interacting with ordinary particles, i.e. possessing properties of invisible (dark) matter.Comment: 24 page

Changes in the gut microbiota of mice orally exposed to methylimidazolium ionic liquids

Ionic liquids are salts used in a variety of industrial processes, and being relatively non-volatile, are proposed as environmentally-friendly replacements for existing volatile liquids. Methylimidazolium ionic liquids resist complete degradation in the environment, likely because the imidazolium moiety does not exist naturally in biological systems. However, there is limited data available regarding their mammalian effects in vivo. This study aimed to examine the effects of exposing mice separately to 2 different methylimidazolium ionic liquids (BMI and M8OI) through their addition to drinking water. Potential effects on key target organs-the liver and kidney-were examined, as well as the gut microbiome. Adult male mice were exposed to drinking water containing ionic liquids at a concentration of 440 mg/L for 18 weeks prior to examination of tissues, serum, urine and the gut microbiome. Histopathology was performed on tissues and clinical chemistry on serum for biomarkers of hepatic and renal injury. Bacterial DNA was isolated from the gut contents and subjected to targeted 16S rRNA sequencing. Mild hepatic and renal effects were limited to glycogen depletion and mild degenerative changes respectively. No hepatic or renal adverse effects were observed. In contrast, ionic liquid exposure altered gut microbial composition but not overall alpha diversity. Proportional abundance of Lachnospiraceae, Clostridia and Coriobacteriaceae spp. were significantly greater in ionic liquid-exposed mice, as were predicted KEGG functional pathways associated with xenobiotic and amino acid metabolism. Exposure to ionic liquids via drinking water therefore resulted in marked changes in the gut microbiome in mice prior to any overt pathological effects in target organs. Ionic liquids may be an emerging risk to health through their potential effects on the gut microbiome, which is implicated in the causes and/or severity of an array of chronic disease in humans

Non-Coding Keratin Variants Associate with Liver Fibrosis Progression in Patients with Hemochromatosis

Background: Keratins 8 and 18 (K8/K18) are intermediate filament proteins that protect the liver from various forms of injury. Exonic K8/K18 variants associate with adverse outcome in acute liver failure and with liver fibrosis progression in patients with chronic hepatitis C infection or primary biliary cirrhosis. Given the association of K8/K18 variants with endstage liver disease and progression in several chronic liver disorders, we studied the importance of keratin variants in patients with hemochromatosis. Methods: The entire K8/K18 exonic regions were analyzed in 162 hemochromatosis patients carrying homozygous C282Y HFE (hemochromatosis gene) mutations. 234 liver-healthy subjects were used as controls. Exonic regions were PCRamplified and analyzed using denaturing high-performance liquid chromatography and DNA sequencing. Previouslygenerated transgenic mice overexpressing K8 G62C were studied for their susceptibility to iron overload. Susceptibility to iron toxicity of primary hepatocytes that express K8 wild-type and G62C was also assessed. Results: We identified amino-acid-altering keratin heterozygous variants in 10 of 162 hemochromatosis patients (6.2%) and non-coding heterozygous variants in 6 additional patients (3.7%). Two novel K8 variants (Q169E/R275W) were found. K8 R341H was the most common amino-acid altering variant (4 patients), and exclusively associated with an intronic KRT8 IVS7+10delC deletion. Intronic, but not amino-acid-altering variants associated with the development of liver fibrosis. I

Modelling state-dependent interference in common cranes

1. Interference is a key component of food competition, but is difficult to measure in natural animal populations. Using data from a long-term study, we show that interference between common cranes Grus grus L., feeding on patches of cereal seeds, reduces intake rates at high competitor densities, and that the strength of interference is unrelated to food abundance. 2. An alternative to measuring interference directly is to predict its strength using behaviour-based models. We test an interference model, originally developed for shorebirds feeding on invertebrate prey, for cranes. We compare the predictions of a rate-maximizing model, in which animals steal food if this increases intake rate, and a state-dependent model, in which they only rate-maximize if their intake rate is below a target value, otherwise they minimize injury risk by not stealing food. State-dependent aggression occurs in cranes. 3. The state-dependent model predicts more accurately the relative aggression rates of cranes of different dominance. However, both models predict accurately the observed strength of interference, that the strength of interference is unrelated to food abundance, at least within the observed range of crane and seed densities, and that cranes of a higher dominance have a higher intake rate than those of lower dominance. 4. This paper shows how state-dependent behaviour can be incorporated into an interference model, and that the model can produce accurate predictions for a system quite different to that for which it was developed.RAS was funded by the Natural Environment Research Council. LMB was partially funded by Ministerio de Ciencia y Tecnología (MCyT) and research grant PB97-1252 of MCyT. Field work was funded by DGICYT project PB87-0389 of the MCyT.Peer reviewe

Application of mineralogical, petrological and geochemical tools for evaluating the palaeohdrogeological evolution of the PADAMOT study sites

The role of Work Package (WP) 2 of the PADAMOT project – ‘Palaeohydrogeological Data Measurements’ - has been to study late-stage fracture mineral and water samples from groundwater systems in Spain, Sweden, United Kingdom and the Czech Republic, with the aim of understanding the recent palaeohydrogeological evolution of these groundwater systems. In particular, the project sought to develop and evaluate methods for obtaining information about past groundwater evolution during the Quaternary (about the last 2 million years) by examining how the late-stage mineralization might record mineralogical, petrographical and geochemical evidence of how the groundwater system may have responded to past geological and climatological changes. Fracture-flow groundwater systems at six European sites were studied: • Melechov Hill, in the Bohemian Massif of the Czech Republic: a shallow (0-100 m) dilute groundwater flow system within the near-surface weathering zone in fractured granitic rocks; • Cloud Hill, in the English Midlands: a (~100 m) shallow dilute groundwater flow system in fractured and dolomitized Carboniferous limestone; • Los Ratones, in southwest Spain: an intermediate depth (0-500 m) dilute groundwater flow system in fractured granitic rocks; • Laxemar, in southeast Sweden: a deep (0-1000 m) groundwater flow system in fractured granitic rocks. This is a complex groundwater system with potential recharge and flushing by glacial, marine, lacustrine and freshwater during the Quaternary; • Sellafield, northwest England: a deep (0-2000 m) groundwater flow system in fractured Ordovician low-grade metamorphosed volcaniclastic rocks and discontinuous Carboniferous Limestone, overlain by a Permo-Triassic sedimentary sequence with fracture and matrix porosity. This is a complex coastal groundwater system with deep hypersaline sedimentary basinal brines, and deep saline groundwaters in crystalline basement rocks, overlain by a shallow freshwater aquifer system. The site was glaciated several times during the Quaternary and may have been affected by recharge from glacial meltwater; • Dounreay, northeast Scotland: a deep (0-1400 m) groundwater flow system in fractured Precambrian crystalline basement overlain by fractured Devonian sedimentary rocks. This is within the coastal discharge area of a complex groundwater system, comprising deep saline groundwater hosted in crystalline basement, overlain by a fracture-controlled freshwater sedimentary aquifer system. Like Sellafield, this area experienced glaciation and may potentially record the impact of glacial meltwater recharge. In addition, a study has been made of two Quaternary sedimentary sequences in Andalusia in southeastern Spain to provide a basis of estimating the palaeoclimatic history of the region that could be used in any reconstruction of the palaeoclimatic history at the Los Ratones site: • The Cúllar-Baza lacustrine sequence records information about precipitation and palaeotemperature regimes, derived largely from the analysis of the stable isotope (δ18O and δ13C) signatures from biogenic calcite (ostracod shells). • The Padul Peat Bog sequence provided information on past vegetation cover and palaeogroundwater inputs based on the study of fossil pollen and biomarkers as proxies for past climate change. Following on from the earlier EC 4th Framework EQUIP project, the focus of the PADAMOT studies has been on calcite mineralization. Calcite has been identified as a late stage mineral, closely associated with hydraulically-conductive fractures in the present-day groundwater systems at the Äspö-Laxemar, Sellafield, Dounreay and Cloud Hill sites. At Los Ratones and Melechov sites late-stage mineralization is either absent or extremely scarce, and both the quantity and fine crystal size of any late-stage fracture mineralization relevant to Quaternary palaeohydrogeological investigations is difficult to work with. The results from the material investigated during the PADAMOT studies indicate that the fracture fillings at these sites are related to hydrothermal activity, and so do not have direct relevance as Quaternary indicators. Neoformed calcite has not been found at these two sites at the present depth of the investigations. Furthermore, the HCO3 - concentration in all the Los Ratones groundwaters is mainly controlled by complex carbonate dissolution. The carbonate mineral saturation indices do not indicate precipitation conditions, and this is consistent with the fact that neoformed calcite, ankerite or dolomite have not been observed petrographically

In severe alcoholic hepatitis, serum keratin-18 fragments are diagnostic, prognostic, and theragnostic biomarkers.

INTRODUCTION: Up to 40% of patients with severe alcoholic hepatitis (AH) die within 6 months of presentation, making prompt diagnosis and appropriate treatment essential. We determined the associations between serum keratin-18 (K18) and histological features, prognosis, and differential response to prednisolone in patients with severe AH. METHODS: Total (K18-M65) and caspase-cleaved K18 (K18-M30) were quantified in pretreatment sera from 824 patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial (87 with suitable histological samples) and disease controls. RESULTS: K18 fragments were markedly elevated in severe AH and strongly predicted steatohepatitis (alcoholic steatohepatitis) on biopsy (area under receiver operating characteristics: 0.787 and 0.807). Application of published thresholds to predict alcoholic steatohepatitis would have rendered biopsy unnecessary in 84% of all AH cases. K18-M30 and M65 were associated with 90-day mortality, independent of age and Model for End-stage Liver Disease score in untreated patients. The association for K18-M65 was independent of both age and Model for End-stage Liver Disease in prednisolone-treated patients. Modelling of the effect of prednisolone on 90-day mortality as a function of pretreatment serum K18 levels indicated benefit in those with high serum levels of K18-M30. At low pretreatment serum K18 levels, prednisolone was potentially harmful. A threshold of K18-M30 5 kIU/L predicted therapeutic benefit from prednisolone above this level (odds ratio: 0.433, 95% confidence interval: 0.19-0.95, P = 0.0398), but not below (odds ratio: 1.271, 95% confidence interval: 0.88-1.84, P = 0.199). Restricting prednisolone usage to the former group would have reduced exposure by 87%. DISCUSSION: In a large cohort of patients with severe AH, serum K18 strongly correlated with histological severity, independently associated with 90-day mortality, and predicted response to prednisolone therapy. Quantification of serum K18 levels could assist in clinical decision-making