Sulfatide in health and disease. The evaluation of sulfatide in cerebrospinal fluid as a possible biomarker for neurodegeneration

Sulfatide (3-O-sulfogalactosylceramide, SM4) is a glycosphingolipid, highly multifunctional and particularly enriched in the myelin sheath of neurons. The role of sulfatide has been implicated in various biological fields such as the nervous system, immune system, host-pathogen recognition and infection, beta cell function and haemostasis/thrombosis. Thus, alterations in sulfatide metabolism and production are associated with several human diseases such as neurological and immunological disorders and cancers. The unique lipid-rich composition of myelin reflects the importance of lipids in this specific membrane structure. Sulfatide has been shown to be involved in the regulation of oligodendrocyte differentiation and in the maintenance of the myelin sheath by influencing membrane dynamics involving sorting and lateral assembly of myelin proteins as well as ion channels. Sulfatide is furthermore essential for proper formation of the axo-glial junctions at the paranode together with axonal glycosphingolipids. Alterations in sulfatide metabolism are suggested to contribute to myelin deterioration as well as synaptic dysfunction, neurological decline and inflammation observed in different conditions associated with myelin pathology (mouse models and human disorders). Body fluid biomarkers are of importance for clinical diagnostics as well as for patient stratification in clinical trials and treatment monitoring. Cerebrospinal fluid (CSF) is commonly used as an indirect measure of brain metabolism and analysis of CSF sulfatide might provide information regarding whether the lipid disruption observed in neurodegenerative disorders is reflected in this body fluid. In this review, we evaluate the diagnostic utility of CSF sulfatide as a biomarker for neurodegenerative disorders associated with dysmyelination/demyelination by summarising the current literature on this topic. We can conclude that neither CSF sulfatide levels nor individual sulfatide species consistently reflect the lipid disruption observed in many of the demyelinating disorders. One exception is the lysosomal storage disorder metachromatic leukodystrophy, possibly due to the genetically determined accumulation of non-metabolised sulfatide. We also discuss possible explanations as to why myelin pathology in brain tissue is poorly reflected by the CSF sulfatide concentration. The previous suggestion that CSF sulfatide is a marker of myelin damage has thereby been challenged by more recent studies using more sophisticated laboratory techniques for sulfatide analysis as well as improved sample selection criteria due to increased knowledge on disease pathology

Attosecond spectroscopy of bio-chemically relevant molecules

Understanding the role of the electron dynamics in the photochemistry of bio-chemically relevant molecules is key to getting access to the fundamental physical processes leading to damage, mutation and, more generally, to the alteration of the final biological functions. Sudden ionization of a large molecule has been proven to activate a sub-femtosecond charge flow throughout the molecular backbone, purely guided by electronic coherences, which could ultimately affect the photochemical response of the molecule at later times. We can follow this ultrafast charge flow in real time by exploiting the extreme time resolution provided by attosecond light sources. In this work recent advances in attosecond molecular physics are presented with particular focus on the investigation of bio-relevant molecules

New symmetries of the chiral Potts model

In this paper a hithertho unknown symmetry of the three-state chiral Potts model is found consisting of two coupled Temperley-Lieb algebras. From these we can construct new superintegrable models. One realisation is in terms of a staggered isotropic XY spin chain. Further we investigate the importance of the algebra for the existence of mutually commuting charges. This leads us to a natural generalisation of the boost-operator, which generates the charges.Comment: 19 pages, improved notation, made the text easier to read, corrected some typo

What makes it work? Exploring experiences of patient research partners and researchers involved in a long-term co-creative research collaboration

Background: Exchanging experiences of patient and public involvement (PPI) can bring insights into why, how and when PPI is most effective. The aim of this study was to explore the experiences of patient research partners (PRPs) and researchers engaged in a co-creative long-term collaboration in cancer research. Methods: The aim and procedures of this study were jointly decided upon by PRPs and researchers. The PRPs included former patients treated for cancer and significant others of the same target group. The participants (11 PRPs, 6 researchers) took part in semi-structured telephone interviews. The interviews were analysed using qualitative content analysis by a researcher who had no prior relationships with the participants. Results: Five overarching categories were identified: Reasons for investing in a long-term collaboration, Benefits of participating, Improving the research, Elements of success and Challenges and ways to improve. Reasons for investing in the collaboration included the desire to improve cancer care and to make use of own negative experiences. Benefits of participating included a positive impact on the PRPs' psychosocial adjustment to the illness. Moreover, the researchers highlighted that working together with the PRPs made the research feel more meaningful. The participants reported that the collaboration improved the relevance and acceptability of the research. Having a shared goal, a clear but yet accommodating structure, as well as an open and trustful working atmosphere were recognised as elements of success. The PRPs furthermore emphasized the importance of seeing that their input mattered. Among the few challenges raised were the distance to the meeting venues for some PRPs and a limited diversity among participants. Conclusions: This study identified factors essential to researchers and clinicians attempting to engage the public in research. Our results suggest that for successful patient involvement, the purpose and format of the collaboration should be clear to both PRPs and researchers. A clear but yet accommodating structure and keen leadership emerged as key factors to create a sense of stability and a trustful atmosphere. Furthermore, providing regular feedback on how PRPs input is implemented is important for PRPs to stay committed over time

Three-Dimensional Fermi Surface of Overdoped La-Based Cuprates

We present a soft x-ray angle-resolved photoemission spectroscopy study of the overdoped high-temperature superconductors La$_{2-x}$Sr$_x$CuO$_4$ and La$_{1.8-x}$Eu$_{0.2}$Sr$_x$CuO$_4$. In-plane and out-of-plane components of the Fermi surface are mapped by varying the photoemission angle and the incident photon energy. No $k_z$ dispersion is observed along the nodal direction, whereas a significant antinodal $k_z$ dispersion is identified. Based on a tight-binding parametrization, we discuss the implications for the density of states near the van-Hove singularity. Our results suggest that the large electronic specific heat found in overdoped La$_{2-x}$Sr$_x$CuO$_4$ can not be assigned to the van-Hove singularity alone. We therefore propose quantum criticality induced by a collapsing pseudogap phase as a plausible explanation for observed enhancement of electronic specific heat

Neutron powder diffraction study of NaMn2_2O4_4 and Li0.92_{0.92}Mn2_2O4_4: New insights on spin-charge-orbital ordering

The high-pressure synthesized quasi-one-dimensional compounds NaMn$_2$O$_4$ and Li$_{0.92}$Mn$_2$O$_4$ are both antiferromagnetic insulators, and here their atomic and magnetic structures were investigated using neutron powder diffraction. The present crystal structural analyses of NaMn2O4 reveal that Mn3+/Mn4+ charge-ordering state exist even at low temperature (down to 1.5 K). It is evident from one of the Mn sites shows a strongly distorted Mn3+ octahedra due to the Jahn-Teller effect. Above TN = 39 K, a two-dimensional short-range correlation is observed, as indicated by an asymmetric diffuse scattering. Below TN, two antiferromagnetic transitions are observed (i) a commensurate long-range Mn3+ spin ordering below 39 K, and (ii) an incommensurate Mn4+ spin ordering below 10 K. The commensurate magnetic structure (kC = 0.5, -0.5, 0.5) follows the magnetic anisotropy of the local easy axes of Mn3+, while the incommensurate one shows a spin-density-wave order with kIC = (0,0,0.216). For Li$_{0.92}$Mn$_2$O$_4$, on the other hand, absence of a long-range spin ordered state down to 1.5 K is confirmed.Comment: 11 pages, 8 figure

The general Leigh-Strassler deformation and integrability

The success of the identification of the planar dilatation operator of N=4 SYM with an integrable spin chain Hamiltonian has raised the question if this also is valid for a deformed theory. Several deformations of SYM have recently been under investigation in this context. In this work we consider the general Leigh-Strassler deformation. For the generic case the S-matrix techniques cannot be used to prove integrability. Instead we use R-matrix techniques to study integrability. Some new integrable points in the parameter space are found.Comment: 22 pages, 8 figures, reference adde

The dual string sigma-model of the SU_q(3) sector

In four-dimensional N=4 super Yang-Mills (SYM) the SU(3) sub-sector spanned by purely holomorphic fields is isomorphic to the corresponding mixed one spanned by both holomorphic and antiholomorphic fields. This is no longer the case when one considers the marginally deformed N=4 SYM. The mixed SU(3) sector marginally deformed by a complex parameter beta, i.e. SU_q(3) with q=e^{2 i\pi\beta}, has been shown to be integrable at one-loop hep-th/0703150, while it is not the case for the corresponding purely holomorphic one. Moreover, the marginally deformed N=4 SYM also has a gravity dual constructed by Lunin and Maldacena in hep-th/0502086. However, the mixed SU_q(3) sector has not been studied from the supergravity point of view. Hence in this note, for the case of purely imaginary marginal $\beta$-deformations, we compute the superstring SU_q(3) \sigma-model in the fast spinning string limit and show that, for rational spinning strings, it reproduces the energy computed via Bethe equations.Comment: 20 page