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

A measurement of the axial form factor of the nucleon by the p(e,e'pi+)n reaction at W=1125 MeV

The reaction p(e,e'pi+)n was measured at the Mainz Microtron MAMI at an invariant mass of W=1125 MeV and four-momentum transfers of Q^2=0.117, 0.195 and 0.273 (GeV/c)^2. For each value of Q^2, a Rosenbluth separation of the transverse and longitudinal cross sections was performed. An effective Lagrangian model was used to extract the `axial mass' from experimental data. We find a value of M_A=(1.077+-0.039) GeV which is (0.051+-0.044) GeV larger than the axial mass known from neutrino scattering experiments. This is consistent with recent calculations in chiral perturbation theory.Comment: 14 pages, 5 figures, uses elsart.cl

Pathogenic Variant Spectrum in Breast Cancer Risk Genes in Finnish Patients

Recurrent pathogenic variants have been detected in several breast and ovarian cancer (BC/OC) risk genes in the Finnish population. We conducted a gene-panel sequencing and copy number variant (CNV) analysis to define a more comprehensive spectrum of pathogenic variants in BRCA1, BRCA2, PALB2, CHEK2, ATM, BARD1, RAD51C, RAD51D, BRIP1, and FANCM genes in Finnish BC patients. The combined frequency of pathogenic variants in the BRCA1/2 genes was 1.8% in 1356 unselected patients, whereas variants in the other genes were detected altogether in 8.3% of 1356 unselected patients and in 12.9% of 699 familial patients. CNVs were detected in 0.3% of both 1137 unselected and 612 familial patients. A few variants covered most of the pathogenic burden in the studied genes. Of the BRCA1/2 carriers, 70.8% had 1 of 10 recurrent variants. In the other genes combined, 92.1% of the carrier patients had at least 1 of 11 recurrent variants. In particular, PALB2 c.1592delT and CHEK2 c.1100delC accounted for 88.9% and 82.9%, respectively, of the pathogenic variation in each gene. Our results highlight the importance of founder variants in the BC risk genes in the Finnish population and could be used in the designing of population screening for the risk variants

Flammability, Smoke, Mechanical Behaviours and Morphology of Flame Retarded Natural Fibre/Elium\uae Composite

The work involves fabrication of natural fibre/Elium\uae composites using resin infusion technique. The jute fabrics were treated using phosphorus-carbon based flame retardant (FR) agent, a phosphonate solution and graphene nano-platelet (GnP), followed by resin infusion, to produce FR and graphene-based composites. The properties of these composites were compared with those of the Control (jute fabric/Elium\uae). As obtained from the cone calorimeter and Fourier transform infrared spectroscopy, the peak heat release rate reduced significantly after the FR and GnP treatments of fabrics whereas total smoke release and quantity of carbon monoxide increased with the incorporation of FR. The addition of GnP had almost no effect on carbon monoxide and carbon dioxide yield. Dynamic mechanical analysis demonstrated that coating jute fabrics with GnP particles led to an enhanced glass transition temperature by 14%. Scanning electron microscopy showed fibre pull-out locations in the tensile fracture surface of the laminates after incorporation of both fillers, which resulted in reduced tensile properties

Generalized seniority scheme in light Sn isotopes

The yrast generalized seniority states are compared with the corresponding shell model states for the case of the Sn isotopes $^{104-112}$Sn. For most of the cases the energies agree within 100 keV and the overlaps of the wave functions are greater than 0.7.Comment: 8 pages, revtex. Submitted to Phys. Rev.

High-precision Studies of the 3^{\bf{3}}He(e,e′^{\bf{\prime}}p) Reaction at the Quasielastic Peak

Precision studies of the reaction $^{3}$He(e,e$^\prime$p) using the three-spectrometer facility at the Mainz microtron MAMI are presented. All data are for quasielastic kinematics at $|\vec{q} | =685$ MeV/c. Absolute cross sections were measured at three electron kinematics. For the measured missing momenta range from 10 to 165 MeV/c, no strength is observed for missing energies higher than 20 MeV. Distorted momentum distributions were extracted for the two-body breakup and the continuum. The longitudinal and transverse behavior was studied by measuring the cross section for three photon polarizations. The longitudinal and transverse nature of the cross sections is well described by a currently accepted and widely used prescription of the off-shell electron-nucleon cross-section. The results are compared to modern three-body calculations and to previous data.Comment: 4 pages, 3 figures. Submitted for publication in Phys. Rev. Let