Motor activity improves temporal expectancy

Certain brain areas involved in interval timing are also important in motor activity. This raises the possibility that motor activity might influence interval timing. To test this hypothesis, we assessed interval timing in healthy adults following different types of training. The pre- and post-training tasks consisted of a button press in response to the presentation of a rhythmic visual stimulus. Alterations in temporal expectancy were evaluated by measuring response times. Training consisted of responding to the visual presentation of regularly appearing stimuli by either: (1) pointing with a whole-body movement, (2) pointing only with the arm, (3) imagining pointing with a whole-body movement, (4) simply watching the stimulus presentation, (5) pointing with a whole-body movement in response to a target that appeared at irregular intervals (6) reading a newspaper. Participants performing a motor activity in response to the regular target showed significant improvements in judgment times compared to individuals with no associated motor activity. Individuals who only imagined pointing with a whole-body movement also showed significant improvements. No improvements were observed in the group that trained with a motor response to an irregular stimulus, hence eliminating the explanation that the improved temporal expectations of the other motor training groups was purely due to an improved motor capacity to press the response button. All groups performed a secondary task equally well, hence indicating that our results could not simply be attributed to differences in attention between the groups. Our results show that motor activity, even when it does not play a causal or corrective role, can lead to improved interval timing judgments

Mapping the Organization of Axis of Motion Selective Features in Human Area MT Using High-Field fMRI

Functional magnetic resonance imaging (fMRI) at high magnetic fields has made it possible to investigate the columnar organization of the human brain in vivo with high degrees of accuracy and sensitivity. Until now, these results have been limited to the organization principles of early visual cortex (V1). While the middle temporal area (MT) has been the first identified extra-striate visual area shown to exhibit a columnar organization in monkeys, evidence of MT's columnar response properties and topographic layout in humans has remained elusive. Research using various approaches suggests similar response properties as in monkeys but failed to provide direct evidence for direction or axis of motion selectivity in human area MT. By combining state of the art pulse sequence design, high spatial resolution in all three dimensions (0.8 mm isotropic), optimized coil design, ultrahigh field magnets (7 Tesla) and novel high resolution cortical grid sampling analysis tools, we provide the first direct evidence for large-scale axis of motion selective feature organization in human area MT closely matching predictions from topographic columnar-level simulations

The development of gene therapy techniques and animal models for Retinitis Pigmentosa and towards the identification of a novel RP-causing gene in a family of Irish origin

THESIS 7344The work presented in this thesis pertains to several different stages in the preclinical development of therapeutics for inherited retinal disease. Chapter two addresses the difficult challenge of delivery of therapeutics to the retina. The technique of subretinal vector delivery is described and successfully illustrated. In addition, a comparison of two different types of viral vectors expressing reporter genes in the retina is described, including an evaluation of the enhancement of reporter gene expression by using immunesupressants. The chapter concludes with an analysis of the therapeutic effect of subretinal delivery, to the rhodopsin knockout mouse (Humphries et al., 1997), of an adeno-associated viral vector expressing rhodopsin. Chapter three describes the generation and characterisation of an animal model of human RP in the mouse. Rhodopsin knockout mice (Humphries et al., 1997) were bred against transgenic mice carrying a Pro-23-His mutant rhodopsin transgene (Olsson JE et al., 1992) producing a mouse expressing the mutant rhodopsin on a Rho-I- background. This new animal (Rho-/-, P23H) was subsequently bred to another transgenic mouse carrying a normal human rhodopsin gene on a rhodopsin knockout background (McNally N et al., 1999). The resulting transgenic mice express both mutant and wild type human rhodopsin at normal levels on a murine Rho-I- background. This mouse will be valuable for testing ribozyme based therapies targeting human rhodopsin sequences. The pathology observed in Rho-/- P23H NHR mice is described. Chapter four describes an extensive study to find the mutated gene in the last known large family of Irish origin segregating with autosomal dominant Retinitis Pigmentosa. A description of some interesting findings at previously described adRP loci in addition to the exclusion of all previously described loci for RP is presented. Also included are the exclusion results of an extensive genome-wide search for the disease causing locus and the sequencing of the PRPF31 gene previously implicated in the pathology of RP

Changes in vascularity and blood volume as a result of photodynamic therapy can be assessed with power Doppler ultrasonography

BACKGROUND AND OBJECTIVES: One principal mechanism of photodynamic therapy (PDT) in tumors is destruction of tumor-associated vasculature. In the present study, the vascular effects of PDT in tumors were investigated with power Doppler ultrasonography. MATERIALS AND METHODS: Seven cutaneous squamous cell carcinomas in cats were treated. Tumors were examined via power Doppler ultrasonography before, 5 minutes, 1 hour, and 24 hours after PDT. Images were digitized for computer-aided assessment of vascularity and blood volume. RESULTS: Mean baseline tumor vascularity and blood volume were moderate. During PDT, a significant decrease in vascularity and blood volume was noted. Lowest values were found 24 hours after PDT. CONCLUSIONS: Power Doppler ultrasonography represents a non-invasive modality to successfully monitor the vascular effects and thus, treatment efficacy, of PDT

A dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvement

Linkage testing using Affymetrix 6.0 SNP Arrays mapped the disease locus in TCD-G, an Irish family with autosomal dominant retinitis pigmentosa (adRP), to an 8.8 Mb region on 1p31. Of 50 known genes in the region, 11 candidates, including RPE65 and PDE4B, were sequenced using di-deoxy capillary electrophoresis. Simultaneously, a subset of family members was analyzed using Agilent SureSelect All Exome capture, followed by sequencing on an Illumina GAIIx platform. Candidate gene and exome sequencing resulted in the identification of an Asp477Gly mutation in exon 13 of the RPE65 gene tracking with the disease in TCD-G. All coding exons of genes not sequenced to sufficient depth by next generation sequencing were sequenced by di-deoxy sequencing. No other potential disease-causing variants were found to segregate with disease in TCD-G. The Asp477Gly mutation was not present in Irish controls, but was found in a second Irish family provisionally diagnosed with choroideremia, bringing the combined maximum two-point LOD score to 5.3. Mutations in RPE65 are a known cause of recessive Leber congenital amaurosis (LCA) and recessive RP, but no dominant mutations have been reported. Protein modeling suggests that the Asp477Gly mutation may destabilize protein folding, and mutant RPE65 protein migrates marginally faster on SDS-PAGE, compared with wild type. Gene therapy for LCA patients with RPE65 mutations has shown great promise, raising the possibility of related therapies for dominant-acting mutations in this gene

Code of practice for electrical energy storage systems

The purpose of this Code of Practice is to provide a reference to practitioners on the safe, effective and competent application of electrical energy storage systems. It also provides an understanding of the common terms and operating modes of electrical energy storage systems. Building on the IET’s technical briefing: Electrical Energy Storage: an Introduction this will also provide detailed information on the specification, design, installation, commissioning, operation and maintenance of an energy storage system. The scope covers all types of electrical and electrochemical energy storage systems; integration into low voltage power systems; industrial, commercial and domestic applications and systems aligned with existing standards, regulations and guidance