Magnetic space groups versus representation analysis in the investigation of magnetic structures: the happy end of a strained relationship.

In recent decades, sustained theoretical and software developments have clearly established that representation analysis and magnetic symmetry groups are complementary concepts that should be used together in the investigation and description of magnetic structures. Historically, they were considered alternative approaches, but currently, magnetic space groups and magnetic superspace groups can be routinely used together with representation analysis, aided by state-of-the-art software tools. After exploring the historical antagonism between these two approaches, we emphasize the significant advancements made in understanding and formally describing magnetic structures by embracing their combined use.

A recapitulation of magnetic space groups and their UNI symbols.

The mathematical structure, description and classification of magnetic space groups is briefly reviewed, with special emphasis on the recently proposed notation, the so-called UNI symbols [Campbell et al. (2022). Acta Cryst. A78, 99-106]. As illustrative examples, very simple magnetic space groups from each of the four possible types are described in detail.

Guidelines for communicating commensurate magnetic structures. A report of the International Union of Crystallography Commission on Magnetic Structures.

A report from the International Union of Crystallography Commission on Magnetic Structures outlining the recommendations for communicating commensurate magnetic structures.

S-adenosyl-L-methionine (SAMe) halts the autoimmune response in patients with primary biliary cholangitis (PBC) via antioxidant and S-glutathionylation processes in cholangiocytes.

S-adenosyl-L-methionine is an endogenous molecule with hepato-protective properties linked to redox regulation and methylation. Here, the potential therapeutic value of SAMe was tested in 17 patients with PBC, a cholestatic disease with autoimmune phenomena targeting small bile ducts. Nine patients responded to SAMe (SAMe responders) with increased serum protein S-glutathionylation. That posttranslational protein modification was associated with reduction of serum anti-mitochondrial autoantibodies (AMA-M2) titers and improvement of liver biochemistry. Clinically, SAMe responders were younger at diagnosis, had longer duration of the disease and lower level of serum S-glutathionylated proteins at entry. SAMe treatment was associated with negative correlation between protein S-glutathionylation and TNFα. Furthermore, AMA-M2 titers correlated positively with INFγ and FGF-19 while negatively with TGFß. Additionally, cirrhotic PBC livers showed reduced levels of glutathionylated proteins, glutaredoxine-1 (Grx-1) and GSH synthase (GS). The effect of SAMe was also analyzed in vitro. In human cholangiocytes overexpressing miR-506, which induces PBC-like features, SAMe increased total protein S-glutathionylation and the level of γ-glutamylcysteine ligase (GCLC), whereas reduced Grx-1 level. Moreover, SAMe protected primary human cholangiocytes against mitochondrial oxidative stress induced by tBHQ (tert-Butylhydroquinone) via raising the level of Nrf2 and HO-1. Finally, SAMe reduced apoptosis (cleaved-caspase3) and PDC-E2 (antigen responsible of the AMA-M2) induced experimentally by glycochenodeoxycholic acid (GCDC). These data suggest that SAMe may inhibit autoimmune events in patients with PBC via its antioxidant and S-glutathionylation properties. These findings provide new insights into the molecular events promoting progression of PBC and suggest potential therapeutic application of SAMe in PBC.

Molecular dynamics simulation of the behaviour of water in nano-confined ionic liquid-water mixtures.

This work describes the behaviour of water molecules in 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid under nanoconfinement, between graphene sheets. By means of molecular dynamics simulations, the adsorption of water molecules at the graphene surface is studied. A depletion of water molecules in the vicinity of the neutral and negatively charged graphene surfaces, and their adsorption at the positively charged surface are observed in line with the preferential hydration of the ionic liquid anions. The findings are appropriately described using a two-level statistical model. The confinement effect on the structure and dynamics of the mixtures is thoroughly analyzed using the density and the potential of mean force profiles, as well as by the vibrational densities of the states of water molecules near the graphene surface. The orientation of water molecules and the water-induced structural transitions in the layer closest to the graphene surface are also discussed.

Symmetry conditions for type II multiferroicity in commensurate magnetic structures.

Type II multiferroics are magnetically ordered phases that exhibit ferroelectricity as a magnetic induced effect. We show that in single-k magnetic phases the presence in the paramagnetic phase of non-symmorphic symmetry combined with some specific type of magnetic propagation vector can be sufficient for the occurrence of this type of multiferroic behaviour. Other symmetry scenarios especially favourable for spin driven multiferroicity are also presented. We review and classify known type II multiferroics under this viewpoint. In addition, some other magnetic phases which due to their symmetry properties can exhibit type II multiferroicity are pointed out.

Monophosphate tungsten bronzes with pentagonal tunnels: reinvestigation through the peephole of the superspace.

The large family of monophosphate tungsten bronzes with pentagonal tunnels (MPTBp), (PO2)4(WO3)2m with m ranging from 4 to 14, can be considered as modular structures via a description with (PO2)2(WO3)m modules related together by a symmetry operation and alternating along the z axis. Following the success of the application of the superspace for the description of the lillianites homologous series, a (3+1)-dimensional superspace model is efficiently defined to unify the structural analysis of the MPTBp. The (3+1)-dimensional model reveals hidden common characteristics such as the symmetry. An evaluation of the model for six well known members of the series was carried out from experimental data collected to this aim.

A fast method for the quantitation of key metabolites of the methionine pathway in liver tissue by high-resolution mass spectrometry and hydrophilic interaction ultra-performance liquid chromatography.

We developed an assay for the extraction and simultaneous quantitation of five key metabolites of the methionine metabolic pathway in liver tissue. The metabolites included were 5'-methylthioadenosine, methionine, homocysteine, S-adenosyl-L-homocysteine, and S-adenosyl-L-methionine. The metabolites were extracted using a bead-based homogenization method, and quantitation was carried out using hydrophilic interaction chromatography and time-of-flight mass spectrometry. The extraction procedure was optimized by testing the effect of various solvent combinations. The chromatographic method was optimized for peak shape, signal intensity, and carry-over. With a total chromatographic run time of 5 min, this assay is suitable for the analysis of large sample sets. Time-of-flight mass spectrometry provided high mass accuracy which, combined with isotope pattern matching and use of chemical standards, guarantees high specificity. Moreover, by operating the mass spectrometer in enhanced duty cycle mode the signal strength for the analytes increased three- to tenfold in comparison with the generic full-scan mode. For quantitation, a matrix-spiked calibration method was used. The lowest analyte levels detected and quantified using our method were within the range of concentrations found in the liver. The inter-day coefficients of variance for the analytes were between 5 and 15% in pooled tissue samples. Interestingly, the CVs between individual liver tissue aliquots were about twice as high. Additional experiments suggested that this higher variability was caused by uneven distribution of the analytes within the liver. In conclusion, an optimized and robust assay is now available for the extraction and quantification of key metabolites in the methionine metabolic pathway.

Spanish human proteome project: dissection of chromosome 16.

The Chromosome 16 Consortium forms part of the Human Proteome Project that aims to develop an entire map of the proteins encoded by the human genome following a chromosome-centric strategy (C-HPP) to make progress in the understanding of human biology in health and disease (B/D-HPP). A Spanish consortium of 16 laboratories was organized into five working groups: Protein/Antibody microarrays, protein expression and Peptide Standard, S/MRM, Protein Sequencing, Bioinformatics and Clinical healthcare, and Biobanking. The project is conceived on a multicenter configuration, assuming the standards and integration procedures already available in ProteoRed-ISCIII, which is encompassed within HUPO initiatives. The products of the 870 protein coding genes in chromosome 16 were analyzed in Jurkat T lymphocyte cells, MCF-7 epithelial cells, and the CCD18 fibroblast cell line as it is theoretically expected that most chromosome 16 protein coding genes are expressed in at least one of these. The transcriptome and proteome of these cell lines was studied using gene expression microarray and shotgun proteomics approaches, indicating an ample coverage of chromosome 16. With regard to the B/D section, the main research areas have been adopted and a biobanking initiative has been designed to optimize methods for sample collection, management, and storage under normalized conditions and to define QC standards. The general strategy of the Chr-16 HPP and the current state of the different initiatives are discussed.

Compositional uniformity, domain patterning and the mechanism underlying nano-chessboard arrays.

We propose that systems exhibiting compositional patterning at the nanoscale, so far assumed to be due to some kind of ordered phase segregation, can be understood instead in terms of coherent, single phase ordering of minority motifs, caused by some constrained drive for uniformity. The essential features of this type of arrangement can be reproduced using a superspace construction typical of uniformity-driven orderings, which only requires the knowledge of the modulation vectors observed in the diffraction patterns. The idea is discussed in terms of a simple two-dimensional lattice-gas model that simulates a binary system in which the dilution of the minority component is favoured. This simple model already exhibits a hierarchy of arrangements similar to the experimentally observed nano-chessboard and nano-diamond patterns, which are described as occupational modulated structures with two independent modulation wavevectors and simple step-like occupation modulation functions.

Structure refinement and superspace description of the system Bi(2(n + 2))Mo(n)O(6(n + 1)) (n = 3, 4, 5 and 6).

The system Bi(2(n + 2))Mo(n)O(6(n + 1)) is described within the superspace formalism. Two superspace models are proposed for the different members of this family, depending on the parity of the parameter n. The superspace model for the odd members is constructed through the embedding of the cationic distribution of the member with n = 3, and the modification of a superspace model previously proposed for the compound Bi(2)MoO(6). However, this model cannot be applied to the even members of the family. Performing the appropriate transformations, a suitable superspace model for the even members is obtained. The atomic structure of the different compounds of the family have been refined through the Rietveld method combining synchrotron X-ray and neutron powder diffraction data.

Unified (3 + 1)-dimensional superspace description of the 2212-type stair-like [Bi2Sr3Fe2O9]m[Bi4Sr6Fe2O16] family of compounds.

The (3 + 1)-dimensional superspace approach is applied to describe and refine a series of sheared compounds related to layered high T(c) superconducting oxides. Two commensurate members (m = 4, 5) of the 2212 stair-like [Bi(2)Sr(3)Fe(2)O(9)](m)[Bi(4)Sr(6)Fe(2)O(16)] family of compounds, previously studied using single-crystal diffraction data, are analyzed. A common average unit cell has been identified and a composition-dependent modulation wavevector is proposed. The model is built using only three independent atomic domains, one for the metal atoms and two for the O atoms. The three Sr, Bi and Fe species are described using close-connected crenel-like functions forming a continuous atomic domain along the internal space. The two oxygen domains are represented by crenel functions and the displacive modulation functions are built up by Legendre polynomials recently implemented in the program JANA2006. Surprisingly, the results of the refinements show a striking similarity of the displacive modulations for the two compounds analyzed, indicating that a unique model can be used to describe the correlations between the atomic displacements of the 2212 stair-like series. This final model is then applied to predict the structure of new members of the family.

Magnetic superspace groups and symmetry constraints in incommensurate magnetic phases.

Superspace symmetry has been for many years the standard approach for the analysis of non-magnetic modulated crystals because of its robust and efficient treatment of the structural constraints present in incommensurate phases. For incommensurate magnetic phases, this generalized symmetry formalism can play a similar role. In this context we review from a practical viewpoint the superspace formalism particularized to magnetic incommensurate phases. We analyse in detail the relation between the description using superspace symmetry and the representation method. Important general rules on the symmetry of magnetic incommensurate modulations with a single propagation vector are derived. The power and efficiency of the method is illustrated with various examples, including some multiferroic materials. We show that the concept of superspace symmetry provides a simple, efficient and systematic way to characterize the symmetry and rationalize the structural and physical properties of incommensurate magnetic materials. This is especially relevant when the properties of incommensurate multiferroics are investigated.

Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression.

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual's level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values=0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.

Symmetry and magnetic field driven transitions in the 2D triangular lattice compound RbFe(MoO4)2.

The temperature versus magnetic field phase diagram of the 2D triangular lattice and multiferroic compound RbFe(MoO(4))(2) is analysed from the point of view of symmetry. The paramagnetic space group and its irreducible representations are used in order to obtain the magnetic symmetry of the possible modulated phases and characterize the restrictions imposed by this symmetry on the corresponding magnetic structures. Superspace symmetry is considered in the case of incommensurate phases. It is shown that the experimentally observed phases correspond to different isotropy subgroups originating in the same irreducible representation of the paramagnetic symmetry group. The relevant couplings between the primary transverse spin modulation and the electric polarization, the in-plane magnetization and the secondary longitudinal magnetic modulation are discussed. The mechanisms for the destabilization of the improper ferroelectric chiral phase and the origin of the different orientation of the spins with respect to the external field in the two collinear phases are analysed from a symmetry based perspective.

Large ferroelectric polarization in the new double perovskite NaLaMnWO6 induced by non-polar instabilities.

Based on density functional theory calculations and group theoretical analysis, we have studied NaLaMnWO(6) compound which has been recently synthesized [G. King, A. Wills and P. M. Woodward, Phys. Rev. B: Condens. Matter, 2009, 79, 224428] and belongs to the AA'BB'O(6) family of double perovskites. At low temperature, the structure has monoclinic P2(1) symmetry, with layered ordering of the Na and La ions and rocksalt ordering of Mn and W ions. The Mn atoms show an antiferromagnetic collinear spin ordering, and the compound has been reported as a potential multiferroic. By comparing the low symmetry structure with a parent phase of P4/nmm symmetry, two distortion modes are found dominant. They correspond to MnO(6) and WO(6) octahedron tilt modes, often found in many simple perovskites. While in the latter these common tilting instabilities yield non-polar phases, in NaLaMnWO(6) the additional presence of the A-A' cation ordering is sufficient to make these rigid unit modes a source of the ferroelectricity. Through a trilinear coupling with the two unstable tilting modes, a polar distortion is induced, although the system has no intrinsic polar instability. The calculated electric polarization resulting from this polar distortion is as large as ∼16 µC cm(-2). Despite its secondary character, this polarization is coupled with the dominant tilting modes and its switching is bound to produce the switching of one of two tilts, enhancing in this way a possible interaction with the magnetic ordering. The transformation of common non-polar purely steric instabilities into sources of ferroelectricity through a controlled modification of the parent structure, as done here by the cation ordering, is a phenomenon to be further explored.

Mode crystallography of distorted structures.

The description of displacive distorted structures in terms of symmetry-adapted modes is reviewed. A specific parameterization of the symmetry-mode decomposition of these pseudosymmetric structures defined on the setting of the experimental space group is proposed. This approach closely follows crystallographic conventions and permits a straightforward transformation between symmetry-mode and conventional descriptions of the structures. Multiple examples are presented showing the insight provided by the symmetry-mode approach. The methodology is shown at work, illustrating its various possibilities for improving the characterization of distorted structures, for example: detection of hidden structural correlations, identification of fundamental and marginal degrees of freedom, reduction of the effective number of atomic positional parameters, quantitative comparison of structures with the same or different space group, detection of false refinement minima, systematic characterization of thermal behavior, rationalization of phase diagrams and various symmetries in families of compounds etc. The close relation of the symmetry-mode description with the superspace formalism applied to commensurate superstructures is also discussed. Finally, the application of this methodology in the field of ab initio or first-principles calculations is outlined. At present, there are several freely available user-friendly computer tools for performing automatic symmetry-mode analyses. The use of these programs does not require a deep knowledge of group theory and can be applied either a posteriori to analyze a given distorted structure or a priori to parameterize the structure to be determined. It is hoped that this article will encourage the use of these tools. All the examples presented here have been worked out using the program AMPLIMODES [Orobengoa et al. (2009). J. Appl. Cryst. 42, 820-833].

Symmetry analysis of extinction rules in diffuse-scattering experiments.

Structured diffuse-scattering intensities, whether of compositional or of pure displacive origin, static or dynamic, contain important information about the symmetry of the individual compositional and/or displacive modes responsible for the observed intensities. However, the interpretation of the experimental data is very often impeded by the lack of a symmetry-based approach to the analysis of the structured diffuse-scattering distributions. Recently, we have demonstrated the existence of systematic phonon selection rules for diffuse scattering that depend on the symmetries of the mode and the scattering vector, and not on the specific structure. Here, we show that such symmetry analysis can be successfully extended and also applied to structure-dependent diffuse scattering associated with 'disordered' materials: the combination of theoretically determined, diffuse-scattering extinction conditions with the concept of non-characteristic orbits proves to be very useful in the interpretation of the observed diffuse-scattering extinctions. The utility of this approach is illustrated by the analysis of diffuse-scattering data from ThAsSe, FeOF and FeF(2). The essential part of the associated calculations are performed by the computer programs NEUTRON (systematic phonon extinction rules in inelastic scattering) and NONCHAR (non-characteristic orbits of space groups) that are available on the Bilbao crystallographic server (http://www.cryst.ehu.es).

The role of stem cells/progenitor cells in liver carcinogenesis in glycine N-methyltransferase deficient mice.

Regeneration of the liver is inhibited as a result of a sustained increase in S-adenosylmethionine levels in glycine N-methyltransferase (GNMT)-/- mice. This sets the stage for normally dormant stem cells/progenitor cells to replicate and differentiate to replenish the liver parenchyma with liver cells. With time the stem cells/progenitor cells may aggregate and ultimately form liver tumors. This transformation of stem cells persists within the tumors that form in order to maintain the growth of the tumors that have formed. To test this hypothesis, GNMT-/- mice were maintained for 18 months and their livers were studied at intervals, in order to document the process of tumors formation and the identification of stem cells/progenitor cells involved in the process. Progenitor cell (OV-6 positive cells) hyperplasia was already established at 8 months in the livers of the GNMT-/- mice. This process was expanded at 18 months when liver tumors had formed. Stem cells which stained positive in the livers at 8 months and within tumors at 18 months (Oct 4 and CK 19 positive cells) were found. Fat 10, a marker for progenitor liver cells, was uniformly expressed by all tumors that developed at 8 and 18 months in GNMT-/- mice.