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Summary Cell surface heparan sulfates modulate many signalling pathways by binding growth factors and growth factor receptors. Expressed in a spatially and temporally regulated manner, these highly sulfated polysaccharides play important roles in all aspects of animal physiology. To understand heparan sulfate-protein binding, it is necessary to develop instrumental sequencing methods. Towards this end, we and others have demonstrated the effectiveness of activated electron dissociation (ExD) tandem mass spectrometry. The value in the ExD approach is that extremely rich tandem mass spectra are produced. The challenge is that bioinformatics methods are needed to convert the raw data into HS saccharide sequences. In this article we describe HS–SEQ, an algorithm developed for this purpose.

PURPOSE: The optokinetic system in healthy humans is a negative-feedback system that stabilizes gaze: slow-phase eye movements (i.e., the output signal) minimize retinal slip (i.e., the error signal). A positive-feedback optokinetic system may exist due to the misrouting of optic fibers. Previous studies have shown that, in a zebrafish mutant with a high degree of the misrouting, the optokinetic response (OKR) is reversed. As a result, slow-phase eye movements amplify retinal slip, forming a positive-feedback optokinetic loop. The positive-feedback optokinetic system cannot stabilize gaze, thus leading to spontaneous eye oscillations (SEOs). Because the misrouting in human patients (e.g., with a condition of albinism or achiasmia) is partial, both positive- and negative-feedback loops co-exist. How this co-existence affects human ocular motor behavior remains unclear. METHODS: We presented a visual environment consisting of two stimuli in different parts of the visual field to healthy subjects. One mimicked positive-feedback optokinetic signals and the other preserved negative-feedback optokinetic signals. By changing the ratio and position of the visual field of these visual stimuli, various optic nerve misrouting patterns were simulated. Eye-movement responses to stationary and moving stimuli were measured and compared with computer simulations. The SEOs were correlated with the magnitude of the virtual positive-feedback optokinetic effect. RESULTS: We found a correlation among the simulated misrouting, the corresponding OKR, and the SEOs in humans. The proportion of the simulated misrouting needed to be greater than 50% to reverse the OKR and at least greater than or equal to 70% to evoke SEOs. Once the SEOs were evoked, the magnitude positively correlated to the strength of the positive-feedback OKR. CONCLUSIONS: This study provides a mechanism of how the misrouting of optic fibers in humans could lead to SEOs, offering a possible explanation for a subtype of infantile nystagmus syndrome (INS).