Trajectory curvature in saccade sequences:spatiotopic influences vs. residual motor activity

Saccades curve away from locations of previous fixation. Varying stimulus timing demonstrates the effects of both 1) spatiotopic representation and 2) motor residual activity from previous saccades. The spatiotopic effect can be explained if current models are augmented with an excitatory top-down spatiotopic signal. When decisions drive saccadic eye movements, traces of the decision process can be inferred from the movement trajectories. For example, saccades can curve away from distractor stimuli, which was thought to reflect cortical inhibition biasing activity in the superior colliculus. Recent neurophysiological work does not support this theory, and two recent models have replaced top-down inhibition with lateral interactions in the superior colliculus or neural fatigue in the brainstem saccadic burst generator. All current models operate in retinotopic coordinates and are based on single saccade paradigms. To extend these models to sequences of saccades, we assessed whether and how saccade curvature depends on previously fixated locations and the direction of previous saccades. With a two-saccade paradigm, we first demonstrated that second saccades curved away from the initial fixation stimulus. Furthermore, by varying the time from fixation offset and the intersaccadic duration, we distinguished the extent of curvature originating from the spatiotopic representation of the previous fixation location or residual motor activity of the previous saccade. Results suggest that both factors drive curvature, and we discuss how these effects could be implemented in current models. In particular, we propose that the collicular retinotopic maps receive an excitatory spatiotopic update from the lateral interparial region

Inhibition of invasion and induction of apoptotic cell death of cancer cell lines by overexpression of TIMP-3

Dysregulation of matrix degrading metalloproteinase enzymes (MMPs) leads to increased extracellular matrix turnover, a key event in the local invasion and metastasis of many tumours. The tissue inhibitors of metalloproteinases (TIMPs) limit the activity of MMPs, which suggests their use in gene therapy. We have previously shown that overexpression of TIMP-1, -2 or -3 inhibits vascular smooth muscle and melanoma cell invasion, while TIMP-3 uniquely promotes apoptosis. We have therefore sought to determine whether TIMP-3 can inhibit invasion and promote apoptosis in other cancer cell types. Adenoviral-mediated overexpression of TIMP-3 inhibited invasion of HeLa and HT1080 cells through artificial basement membrane to similar levels as that achieved by TIMP-1 and -2. However, TIMP-3 uniquely promoted cell cycle entry and subsequent death by apoptosis. Apoptosis was confirmed by morphological analysis, terminal dUTP nick end labelling (TUNEL) and flow cytometry. The apoptotic phenotype was mimicked by addition of exogenous recombinant TIMP-3 to uninfected cultures demonstrating that the death signal is initiated extracellularly and that a bystander effect exists. These results show that TIMP-3 inhibits invasion in vitro and promotes apoptosis in cancer cell type of differing origin. This clearly identifies the potential of TIMP-3 for gene therapy of multiple cancer types. © 1999 Cancer Research Campaig

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

Two Chromatin Remodeling Activities Cooperate during Activation of Hormone Responsive Promoters

Steroid hormones regulate gene expression by interaction of their receptors with hormone responsive elements (HREs) and recruitment of kinases, chromatin remodeling complexes, and coregulators to their target promoters. Here we show that in breast cancer cells the BAF, but not the closely related PBAF complex, is required for progesterone induction of several target genes including MMTV, where it catalyzes localized displacement of histones H2A and H2B and subsequent NF1 binding. PCAF is also needed for induction of progesterone target genes and acetylates histone H3 at K14, an epigenetic mark that interacts with the BAF subunits by anchoring the complex to chromatin. In the absence of PCAF, full loading of target promoters with hormone receptors and BAF is precluded, and induction is compromised. Thus, activation of hormone-responsive promoters requires cooperation of at least two chromatin remodeling activities, BAF and PCAF

Histone H1 Subtypes Differentially Modulate Chromatin Condensation without Preventing ATP-Dependent Remodeling by SWI/SNF or NURF

Although ubiquitously present in chromatin, the function of the linker histone subtypes is partly unknown and contradictory studies on their properties have been published. To explore whether the various H1 subtypes have a differential role in the organization and dynamics of chromatin we have incorporated all of the somatic human H1 subtypes into minichromosomes and compared their influence on nucleosome spacing, chromatin compaction and ATP-dependent remodeling. H1 subtypes exhibit different affinities for chromatin and different abilities to promote chromatin condensation, as studied with the Atomic Force Microscope. According to this criterion, H1 subtypes can be classified as weak condensers (H1.1 and H1.2), intermediate condensers (H1.3) and strong condensers (H1.0, H1.4, H1.5 and H1x). The variable C-terminal domain is required for nucleosome spacing by H1.4 and is likely responsible for the chromatin condensation properties of the various subtypes, as shown using chimeras between H1.4 and H1.2. In contrast to previous reports with isolated nucleosomes or linear nucleosomal arrays, linker histones at a ratio of one per nucleosome do not preclude remodeling of minichromosomes by yeast SWI/SNF or Drosophila NURF. We hypothesize that the linker histone subtypes are differential organizers of chromatin, rather than general repressors

Angular and Current-target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic e+ p scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation