We undertook a neurophysiological investigation of the responses of low-threshold mechanoreceptors in the human finger pad to surfaces of differing softness. Unitary recordings were made from 26 ...slowly adapting type I (SAI), 17 fast-adapting type I (FAI), and 9 slowly adapting type II (SAII) afferents via tungsten microelectrodes inserted into the median nerve at the wrist. A servo-controlled stimulator applied ramp-and-hold forces (1, 2, 4 N) at a constant loading and unloading rate (2 N/s) via a flat silicone disc over the center of the finger pad. Nine discs were used, which linearly increased in stiffness across the range. Population responses of the SAI afferents showed the greatest sensitivity to compliance, with a steep monotonic increase in mean firing rate with increasing stiffness (decreasing compliance) of the surface during the loading and plateau (but not unloading) phases. FAI afferents also showed a linear increase in firing during the loading but not unloading phase, although the slope was significantly lower than that of the SAI afferents at all amplitudes. Conversely, SAII afferents were influenced by object compliance only in certain conditions. Given their high density in the finger pads and their linear relationship between firing rate and object compliance during the loading and plateau phases, SAI afferents (together with FAI afferents during the loading phase) are ideally suited to contributing information on surface compliance to the overall estimation of softness, but the SAII afferents appear to play only a minor role.
A new class of glutathione transferases has been discovered by analysis of the expressed sequence tag data base and sequence alignment. Glutathione S-transferases (GSTs) of the new class, named ...Omega, exist in several mammalian species andCaenorhabditis elegans. In humans, GSTO 1-1 is expressed in most tissues and exhibits glutathione-dependent thiol transferase and dehydroascorbate reductase activities characteristic of the glutaredoxins. The structure of GSTO 1-1 has been determined at 2.0-Å resolution and has a characteristic GST fold (Protein Data Bank entry code 1eem). The Omega class GSTs exhibit an unusual N-terminal extension that abuts the C terminus to form a novel structural unit. Unlike other mammalian GSTs, GSTO 1-1 appears to have an active site cysteine that can form a disulfide bond with glutathione.
Using a multi-channel platinum surface electrode array, recordings from cat primary visual cortex were obtained in response to visual stimuli, and electrical stimuli delivered using the elements of ...the array itself. Neural responses to electrical stimuli were consistent, regardless of stimulus polarity or leading phase (biphasic), although thresholds were lower for monophasic than biphasic pulses. Both visual and electrical stimuli reliably evoked responses with characteristic components, which interacted with each other in a nonlinear summation showing first facilitation then suppression during the window of interaction. The chronaxie for eliciting threshold cortical responses was about 100 mus, and the charge density with a pulse width of 50-100 mus was around 55 muC cm(-2). These data form the basis of understanding the types of cortical responses to stimuli delivered by devices suitable for chronic implantation.
Wholemounting is a standard procedure used to view the retinal organization in light microscopic studies. Radial cuts are made into the retina from its perimeter to allow it to be flattened onto a ...glass slide. This process distorts the retina and introduces missing pie (phantom) sectors into the wholemount. Distortion in the retinal wholemount has been quantified by modeling the retina as a hemisphere transformed into a disc interrupted with phantom sectors. The interrupted continuity of the retinal wholemount indicates that an angle subtended at the center of the wholemount must be smaller than its corresponding angle in the intact retina. In the model presented here (H–D transform) a method is described for interconverting angles between the hemisphere and the wholemount and for transforming any point on the wholemount back onto the surface of the hemisphere. Computations on the model show that the angles, subtended by phantom sectors at the center of a wholemounted retina, on a given concentric circle can be quantified and summed to a constant value. The value depends on and monotonically increases with eccentricity, it is nil at the center of the wholemount and maximal at the retinal margin. As a result, radial cuts made in the periphery of the wholemount need not extend into its center. In addition, sector edges of the wholemount are approximated by quarter wave sinusoids, larger sectors having greater amplitude and consequently greater distortion. Moreover, a large piece of tissue exerts more spring recoil and thus in large retinas relatively more cuts are required in the wholemount. However, the total angle deficit of the phantom sectors around the circumference of the wholemount is unaffected by the radius of the eye. A standard configuration for the wholemount is defined that minimizes the overall error in orientation for any sector.
The stain toluidine blue-O (tol blue), applied to sections of neural tissue, is shown to be compatible with the vivid fluorescent lipophilic neural tracers 4-(4-dihexadecylaminostyryl)-
...N-methylpyridinium iodide (Di-ASP), 3,3′-dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). As with other Nissl stains, toluidine blue-O fluoresces in the red end of the spectrum but such fluorescence quenches upon binding with tissue. Moreover, progressive staining occurs at concentrations low enough to minimise any background fluorescence attributable to non-specific residence of the stain. The bright yellow Di-ASP and vivid green DiO signals are spectrally removed from the red fluorescence of toluidine blue-O. With toluidine blue-O counterstaining, Di-ASP generally offers contrast superior to that with DiI, however, the latter is improved by viewing in a polarised green bright field. Visible Di-ASP emission, although broad, peaks at a more film-sensitive region of the spectrum than that for DiI, thus reducing the photographic exposure required.
Two monkeys were trained in a novel version of a delayed match-to-sample (DMS) task. They were required to fixate on a small spot at the center of the monitor and distinguish whether two gratings ...presented one after the other with delays up to 1.5 s in a specific visual field location were similar or not. It was found that such learning fails to transfer readily to other retinal locations. In fact, the learning was sensitive even to very small retinal displacements of the visual stimuli. Such acute retinal position specificity implies that at least a component of the learning in this particular memory task occurs at an early visual area such as the striate cortex, which has a fine-grain topographical representation. Furthermore, at early stages of learning the DMS task, when the monkeys had not generalized the learning to stimuli of different sizes, they failed to show size constancy. That is, when the display was placed at a different distance but with the same absolute size, the performance dropped. The performance was almost fully restored when, at the new display location, stimuli were changed to fit the original retinal size. This indicates that a crucial component of the learning does occur at a site even prior to size constancy. These results show that, under certain situations, an early visual area such as the primary visual cortex may be involved even in complex behaviours such as a memory task as more than just a feature-detecting area or a relay station.
Background: Glutathione S-transferases (GSTs) comprise a multifunctional group of enzymes that play a critical role in the cellular detoxification process. These enzymes reduce the reactivity of ...toxic compounds by catalyzing their conjugation with glutathione. As a result of their role in detoxification, GSTs have been implicated in the development of cellular resistance to antibiotics, herbicides and clinical drugs and their study is therefore of much interest. In mammals, the cytosolic GSTs can be divided into five distinct classes termed alpha, mu, pi, sigma and theta. The human theta class GST, hGST T2-2, possesses several distinctive features compared to GSTs of other classes, including a long C-terminal extension and a specific sulfatase activity. It was hoped that the determination of the structure of hGST T2-2 may help us to understand more about this unusual class of enzymes.
Results: Here we present the crystal structures of hGST T2-2 in the apo form and in complex with the substrates glutathione and 1-menaphthyl sulfate. The enzyme adopts the canonical GST fold with a 40-residue C-terminal extension comprising two helices connected by a long loop. The extension completely buries the substrate-binding pocket and occludes most of the glutathione-binding site. The enzyme has a purpose-built novel sulfate-binding site. The crystals were shown to be catalytically active: soaks with 1-menaphthyl sulfate result in the production of the glutathione conjugate and cleavage of the sulfate group.
Conclusions: hGST T2-2 shares less than 15% sequence identity with other GST classes, yet adopts a similar three-dimensional fold. The C-terminal extension that blocks the active site is not disordered in either the apo or complexed forms of the enzyme, but nevertheless catalysis occurs in the crystalline state. A narrow tunnel leading from the active site to the surface may provide a pathway for the entry of substrates and the release of products. The results suggest a molecular basis for the unique sulfatase activity of this GST.
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