Motor recovery following capsular stroke

The functional anatomy of motor recovery was studied by assessing motor function quantitatively in 23 patients following capsular or striatocapsular stroke. While selective basal ganglia lesions (caudate and/or putamen exclusively) did not affect voluntary movements of the extremities, lesions of the anterior (plus caudate/putamen) or posterior limb of the internal capsule led to an initially severe motor impairment followed by excellent recovery, hand function included. In contrast, lesions of the posterior limb of the internal capsule in combination with damage to lateral thalamus compromised motor outcome. In experimental tracing of the topography of the internal capsule in macaque monkeys, we found axons of primary motor cortex passing through the middle third of the posterior limb of the internal capsule. Axons of premotor cortex (dorsolateral and post-arcuate area 6) passed through the capsular genu, and those of supplementary motor area (mesial area 6) through the anterior limb. Small capsular lesion can therefore disrupt the output of functionally and anatomically distinct motor areas selectively. The clinically similar motor deficits with a similar course of functional restitution following disruption of these different descending motor pathways indicate a parallel operation of cortical motor areas. They may have the further capability of substituting each other functionally in the process of recovery from hemiparesis

AATF, a novel transcription factor that interacts with Dlk/ZIP kinase and interferes with apoptosis11Accession no. for rat AATF nucleotide sequence at the EMBL GenBank database is RNO238717.

AbstractDlk, also known as ZIP kinase, is a serine/threonine kinase that is tightly associated with nuclear structures. Under certain conditions, which require cytoplasmic localization, Dlk can induce apoptosis. In search for interaction partners that might serve as regulators or targets of this kinase we identified apoptosis antagonizing transcription factor (AATF), a nuclear phosphoprotein of 523 amino acids. The 1.8 kb mRNA seems to be ubiquitously expressed. AATF contains an extremely acidic domain and a putative leucine zipper characteristic of transcription factors. Indeed, a Gal4-BD-AATF fusion protein exhibited strong transactivation activity. Interestingly, AATF interfered with Dlk-induced apoptosis

Intrachromosomal recombination mediated by the polyomavirus large T antigen

AbstractWe used a spleen necrosis virus-based retroviral vector to introduce the polyomavirus replication origin into rat cells and developed a system to analyze homologous recombination events that do not reconstitute a selectable marker. Introduction of the gene coding for the polyomavirus large T antigen into the cell lines by DNA transfection promoted high-frequency recombination between the two retroviral LTRs, leading to amplification and excision of DNA sequences. To analyze homology requirements, we constructed cell lines carrying only the replication origin without exogenous repeats. Most of the cell lines sustained high-frequency recombination, presumably by undergoing homologous recombination between repetitive DNA lying in the vicinity of the integrated origin. Our results indicate that homologous recombination promoted by large T antigen does not require recombination hot spots in the viral genome other than the replication origin and they explain the cytotoxicity observed in some cell types when large T antigen is expressed in the presence of a functional origin

Immunochemical and electrophysiological characterization of murine connexin40 and -43 in mouse tissues and transfected human cells

Human HeLa or SkHep1 cells, defective in intercellular communication through gap junctions, were transfected with coding sequences of murine connexin40 (Cx40) and -43. The transfected cells were restored in gap junctional coupling as shown by 100-fold increased electrical conductance. When studied by the double whole-cell patch-clamp technique, Cx40 HeLa transfectans exhibited single channel conductances of γ=121 ± 7 pS and γ=153 ± 5 pS. They were voltage gated with an equivalent gating charge of z=4.0 ± 0.5 for a voltage of half-maximal inactivation U 9= 44 ± 7 mV. The corresponding values or connexin43 (Cx43) HeLa transfectants are: γ=60 ± 4 pS and γ=40 ± 2 pS as well as z=3.7 ± 0.8 and U 0 = 73 ± 7 mV. Transfer of the dye Lucifer Yellow was always considerably lower in Cx4- than in Cx43-transfectants though their total junctional conductance was similar or even higher than for Cx43-transfectants

The DARS (Dopamine Augmented Rehabilitation in Stroke) trial: protocol for a randomised controlled trial of Co-careldopa treatment in addition to routine NHS occupational and physical therapy after stroke

Background: Stroke has a huge impact, leaving more than a third of affected people with lasting disability and rehabilitation remains a cornerstone treatment in the National Health Service (NHS). Recovery of mobility and arm function post-stroke occurs through re-learning to use the affected body parts and/or learning to compensate with the lesser affected side. Promising evidence suggests that the addition of Co-careldopa to physical therapy and occupational therapy may improve the recovery of arm and leg movement and lead to improved function. Methods/design: Dopamine Augmented Rehabilitation in Stroke (DARS) is a multi-centre double-blind, randomised, placebo, controlled clinical trial of Co-careldopa in addition to routine NHS occupational therapy and physical therapy as part of early stroke rehabilitation. Participants will be randomised on a 1:1 basis to either Co-careldopa or placebo. The primary objective of the trial is to determine whether the addition of six weeks of Co-careldopa treatment to rehabilitation therapy can improve the proportion of patients who can walk independently eight weeks post-randomisation. Discussion: The DARS trial will provide evidence as to whether Co-careldopa, in addition to routine NHS occupational and physical therapy, leads to a greater recovery of motor function, a reduction in carer dependency and advance rehabilitation treatments for people with stroke. Trial registration: ISRCTN99643613 assigned on 4 December 2009

Design of Selective Gas Sensors Using Additive-Loaded In2O3 Hollow Spheres Prepared by Combinatorial Hydrothermal Reactions

A combinatorial hydrothermal reaction has been used to prepare pure and additive (Sb, Cu, Nb, Pd, and Ni)-loaded In2O3 hollow spheres for gas sensor applications. The operation of Pd- and Cu-loaded In2O3 sensors at 371 °C leads to selective H2S detection. Selective detection of CO and NH3 was achieved by the Ni-In2O3 sensor at sensing temperatures of 371 and 440 °C, respectively. The gas responses of six different sensors to NH3, H2S, H2, CO and CH4 produced unique gas sensing patterns that can be used for the artificial recognition of these gases

Structural Basis of PP2A Inhibition by Small t Antigen

The SV40 small t antigen (ST) is a potent oncoprotein that perturbs the function of protein phosphatase 2A (PP2A). ST directly interacts with the PP2A scaffolding A subunit and alters PP2A activity by displacing regulatory B subunits from the A subunit. We have determined the crystal structure of full-length ST in complex with PP2A A subunit at 3.1 Å resolution. ST consists of an N-terminal J domain and a C-terminal unique domain that contains two zinc-binding motifs. Both the J domain and second zinc-binding motif interact with the intra-HEAT-repeat loops of HEAT repeats 3–7 of the A subunit, which overlaps with the binding site of the PP2A B56 subunit. Intriguingly, the first zinc-binding motif is in a position that may allow it to directly interact with and inhibit the phosphatase activity of the PP2A catalytic C subunit. These observations provide a structural basis for understanding the oncogenic functions of ST