Characterization and identification of dityrosine cross-linked peptides using tandem mass spectrometry

The use of mass spectrometry coupled with chemical cross-linking of proteins has become a powerful tool for proteins structure and interactions studies. Unlike structural analysis of proteins using chemical reagents specific for lysine or cysteine residues, identification of gas-phase fragmentation patterns of endogenous dityrosine cross-linked peptides have not been investigated. Dityrosine cross-linking in proteins and peptides are clinical markers of oxidative stress, aging, and neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. In this study, we investigated and characterized the fragmentation pattern of a synthetically prepared dityrosine cross-linked dimer of Aβ(1–16) using ESI tandem mass spectrometry. We then detailed the fragmentation pattern of dityrosine cross-linked Aβ(1–16), using collision induced dissociation (CID), higher-energy collision induced dissociation (HCD), electron transfer dissociation (ETD), and electron capture dissociation (ECD). Application of these generic fragmentation rules of dityrosine cross-linked peptides allowed for the identification of dityrosine cross-links in peptides of Aβ and α-synuclein generated in vitro by enzymatic peroxidation. We report, for the first time, the dityrosine cross-linked residues in human hemoglobin and α-synuclein under oxidative conditions. Together these tools open up the potential for automated analysis of this naturally occurring post-translation modification in neurodegenerative diseases as well as other pathological conditions

Changes in serum neurofilament light chain levels following narrowband ultraviolet B phototherapy in clinically isolated syndrome

Objective To determine whether serum neurofilament light chain (sNfL) levels are suppressed in patients with the clinically isolated syndrome (CIS) following narrowband ultraviolet B phototherapy (UVB-PT). Methods sNfL levels were measured using a sensitive single-molecule array assay at baseline and up to 12 months in 17 patients with CIS, 10 of whom received UVB-PT, and were compared with healthy control (HC) and early relapsing remitting multiple sclerosis (RRMS) group. sNfL levels were correlated with magnetic resonance imaging total lesion volume (LV) determined using icobrain version 4.4.1 and with clinical outcomes. Results Baseline median sNfL levels were significantly higher in the CIS (20.6 pg/mL, interquartile range [IQR] 13.7–161.4) and RRMS groups (36.6 pg/ml [IQR] 16.2–212.2) than in HC (10.7 pg/ml [IQR] 4.9–21.5) (p = .012 and p = .0002, respectively), and were strongly correlated with T2 and T1 LV at 12 months (r = .800; p = .014 and r = .833; p = .008, respectively) in the CIS group. Analysis of changes in sNfL levels over time in the CIS group showed a significant cumulative suppressive effect of UVB-PT in the first 3 months (UVB-PT −10.6% vs non-UVB-PT +58.3%; p = .04) following which the levels in the two groups converged and continued to fall. Conclusions Our findings provide the basis for further studies to determine the utility of sNfL levels as a marker of neuro-axonal damage in CIS and early MS and for assessing the efficacy of new therapeutic interventions such as UVB-PT

Survey of nucleon electromagnetic form factors

A dressed-quark core contribution to nucleon electromagnetic form factors is calculated. It is defined by the solution of a Poincare' covariant Faddeev equation in which dressed-quarks provide the elementary degree of freedom and correlations between them are expressed via diquarks. The nucleon-photon vertex involves a single parameter; i.e., a diquark charge radius. It is argued to be commensurate with the pion's charge radius. A comprehensive analysis and explanation of the form factors is built upon this foundation. A particular feature of the study is a separation of form factor contributions into those from different diagram types and correlation sectors, and subsequently a flavour separation for each of these. Amongst the extensive body of results that one could highlight are: r_1^{n,u}>r_1^{n,d}, owing to the presence of axial-vector quark-quark correlations; and for both the neutron and proton the ratio of Sachs electric and magnetic form factors possesses a zero.Comment: 43 pages, 17 figures, 12 tables, 5 appendice

Acute Haemodynamic Changes During Haemodialysis Do Not Exacerbate Gut Hyperpermeability

© 2019 The Author(s)Introduction: The gastrointestinal tract is a potential source of inflammation in dialysis patients. In-vitro studies suggest breakdown of the gut barrier in uraemia leading to increased intestinal permeability and it is hypothesised that haemodialysis exacerbates this problem due to mesenteric ischemia induced by blood volume changes during treatment. Method: The effect of haemodialysis on intestinal permeability was studied in ten haemodialysis patients and compared with five controls. Intestinal permeability was assessed by measuring the differential absorption of four orally administered sugar probes which provides an index of small and whole bowel permeability. A multi-sugar solution (containing lactulose, rhamnose, sucralose and erythritol) was orally administered after an overnight fast. Plasma levels of all sugar probes were measured hourly for 10hrs post-administration. In haemodialysis patients, the procedure was carried out twice – once on a non-dialysis day and once immediately after haemodialysis. Results: Area under curve (AUC) for lactulose: rhamnose (L:R) ratio and sucralose: erythritol (S:E) ratio was similar post-dialysis and on non-dialysis days. AUC for L:R was higher in haemodialysis patients compared to controls (0.071 vs. 0.034,p=0.001), AUC for S:E ratio was not significantly different. Levels of lactulose, sucralose and erythritol were elevated and retained for longer in haemodialysis patients compared to controls due to dependence of sugars on kidney function for clearance. Conclusion: We found no significant acute changes in intestinal permeability in relation to the haemodialysis procedure. Valid comparison of intestinal permeability between controls and haemodialysis patients was not possible due to the strong influence of kidney function on sugar levels.Peer reviewedFinal Published versio

Guidelines for the Selection of Physical Literacy Measures in Physical Education in Australia

Assessment of physical literacy poses a dilemma of what instrument to use. There is currently no guide regarding the suitability of common assessment approaches. The purpose of this brief communication is to provide a user's guide for selecting physical literacy assessment instruments appropriate for use in school physical education and sport settings. While recommendations regarding specific instruments are not provided, the guide offers information about key attributes and considerations for the use. A decision flow chart has been developed to assist teachers and affiliated school practitioners to select appropriate methods of assessing physical literacy. School PE and sport scenarios are presented to illustrate this process. It is important that practitioners are empowered to select the most appropriate instrument/s to suit their needs

Defining Physical Literacy for Application in Australia: A Modified Delphi Method

Purpose. The development of a physical literacy definition and standards framework suitable for implementation in Australia. Method. Modified Delphi methodology. Results . Consensus was established on four defining statements: Core – Physical literacy is lifelong holistic learning acquired and applied in movement and physical activity contexts; Composition – Physical literacy reflects ongoing changes integrating physical, psychological, cognitive and social capabilities; Importance – Physical literacy is vital in helping us lead healthy and fulfilling lives through movement and physical activity; Aspiration – A physically literate person is able to draw on their integrated physical, psychological, cognitive, and social capacities to support health promoting and fulfilling movement and physical activity, relative to their situation and context, throughout the lifespan. The standards framework addressed four learning domains (physical, psychological, cognitive, and social), spanning five learning configurations/levels. Conclusion. The development of a bespoke program for a new context has important implications for both existing and future program

How spiking neurons give rise to a temporal-feature map

A temporal-feature map is a topographic neuronal representation of temporal attributes of phenomena or objects that occur in the outside world. We explain the evolution of such maps by means of a spike-based Hebbian learning rule in conjunction with a presynaptically unspecific contribution in that, if a synapse changes, then all other synapses connected to the same axon change by a small fraction as well. The learning equation is solved for the case of an array of Poisson neurons. We discuss the evolution of a temporal-feature map and the synchronization of the single cells’ synaptic structures, in dependence upon the strength of presynaptic unspecific learning. We also give an upper bound for the magnitude of the presynaptic interaction by estimating its impact on the noise level of synaptic growth. Finally, we compare the results with those obtained from a learning equation for nonlinear neurons and show that synaptic structure formation may profit from the nonlinearity

News from the Muon (g-2) Experiment at BNL

The magnetic moment anomaly a_mu = (g_mu - 2) / 2 of the positive muon has been measured at the Brookhaven Alternating Gradient Synchrotron with an uncertainty of 0.7 ppm. The new result, based on data taken in 2000, agrees well with previous measurements. Standard Model evaluations currently differ from the experimental result by 1.6 to 3.0 standard deviations.Comment: Talk presented at RADCOR - Loops and Legs 2002, Kloster Banz, Germany, September 8-13 2002, to be published in Nuclear Physics B (Proc. Suppl.); 5 pages, 3 figure