Showing papers by "Rob Knight published in 2003"

Does the representation of time depend on the cerebellum?Effect of cerebellar stroke

Abstract: Behaviours that appear to depend on processing temporal information are frequently disrupted after cerebellar damage. The present study examined the role of the cerebellum in explicit timing and its relationship to other psychological processes. We hypothesized that if the cerebellum regulates timekeeping operations then cerebellar damage should disrupt the perception and the reproduction of intervals, since both are thought to be supported by a common timekeeper mechanism. Twenty-one patients with cerebellar damage from stroke and 30 normal controls performed time perception and time reproduction tasks. In the time reproduction task, timing variability was decomposed into a central timing component (clock variability) and a motor component (motor implementation variability). We found impairments only in time reproduction (increased clock variability) in patients with medial and lateral damage involving the middle- to superior-cerebellar lobules. To explore potential reasons for the temporal processing deficits, time reproduction and perception performance were correlated with independent measures of attention, working memory, sensory discrimination and processing speed. Poorer working memory correlated with increased variability in the 'clock' component of time reproduction. In contrast, processing speed correlated best with time perception. The results did not support a role for the cerebellum in timekeeping operations. Rather, deficits in timing movements may be related to a disruption in acquiring sensory and cognitive information relevant to the task, coupled with an additional impairment in the motor-output system.

lockjaw encodes a zebrafish tfap2a required for early neural crest development.

Abstract: The neural crest is a uniquely vertebrate cell type that gives rise to much of the craniofacial skeleton, pigment cells and peripheral nervous system, yet its specification and diversification during embryogenesis are poorly understood. Zebrafish homozygous for the lockjaw (low) mutation show defects in all of these derivatives and we show that low (allelic with montblanc) encodes a zebrafish tfap2a, one of a small family of transcription factors implicated in epidermal and neural crest development. A point mutation in low truncates the DNA binding and dimerization domains of tfap2a, causing a loss of function. Consistent with this, injection of antisense morpholino oligonucleotides directed against splice sites in tfap2a into wild-type embryos produces a phenotype identical to low. Analysis of early ectodermal markers revealed that neural crest specification and migration are disrupted in low mutant embryos. TUNEL labeling of dying cells in mutants revealed a transient period of apoptosis in crest cells prior to and during their migration. In the cranial neural crest, gene expression in the mandibular arch is unaffected in low mutants, in contrast to the hyoid arch, which shows severe reductions in dlx2 and hoxa2 expression. Mosaic analysis, using cell transplantation, demonstrated that neural crest defects in low are cell autonomous and secondarily cause disruptions in surrounding mesoderm. These studies demonstrate that low is required for early steps in neural crest development and suggest that tfap2a is essential for the survival of a subset of neural crest derivatives.

Finding specific RNA motifs: function in a zeptomole world?

Abstract: We have developed a new method for estimating the abundance of any modular (piecewise) RNA motif within a longer random region. We have used this method to estimate the size of the active motifs available to modern SELEX experiments (picomoles of unique sequences) and to a plausible RNA World (zeptomoles of unique sequences: 1 zmole = 602 sequences). Unexpectedly, activities such as specific isoleucine binding are almost certainly present in zeptomoles of molecules, and even ribozymes such as self-cleavage motifs may appear (depending on assumptions about the minimal structures). The number of specified nucleotides is not the only important determinant of a motif’s rarity: The number of modules into which it is divided, and the details of this division, are also crucial. We propose three maxims for easily isolated motifs: the Maxim of Minimization, the Maxim of Multiplicity, and the Maxim of the Median. These maxims together state that selected motifs should be small and composed of as many separate, equally sized modules as possible. For evenly divided motifs with four modules, the largest accessible activity in picomole scale (1–1000 pmole) pools of length 100 is about 34 nucleotides; while for zeptomole scale (1–1000 zmole) pools it is about 20 specific nucleotides (50% probability of occurrence). This latter figure includes some ribozymes and aptamers. Consequently, an RNA metabolism apparently could have begun with only zeptomoles of RNA molecules.

Analyzing partially randomized nucleic acid pools: straight dope on doping

Abstract: Partially randomized (doped) pools are important for optimizing activities initially isolated by selection-amplification or SELEX, and for locating nucleotides critical for function. Here we present a method for calculating the number of unique sequences in a pool, and the expected copy number of each unique sequence with a specified number of changes from the original sequence. Surprisingly, small differences in doping can have large consequences for the number of copies of sequences with certain numbers of changes from the original sequence. We demonstrate the effects of pool size, percentage doping, length of the random region and taking aliquots from the original pool on the exploration of sequence space in a doped reselection experiment. A web form is provided for customized calculations.

Grouping Influences in Unilateral Visual Neglect

Abstract: Effects of grouping on unilateral neglect were investigated in 8 neurological patients with right hemisphere damage. It is well documented that arranging items to form a group spanning the midline decreases the magnitude of neglect. In the present study we examined how clusters of groups within the left or right visual field affect neglect and whether isolated groups within the neglected field deflect attention from right-sided displays. We orthogonally varied the strength of grouping on the right and left sides of a display and measured the time to find a predesignated target in one of those groups. Groups on the neglected left side did not affect right-sided target detection any more than an empty left page. However, strength of grouping did affect left sided target detection. These findings are discussed as they relate to attention and preattention in unilateral visual neglect.