The neural development and organization of letter recognition: Evidence from functional neuroimaging, computational modeling, and behavioral studies

Although much of the brain’s functional organization is genetically predetermined, it appears that some noninnate functions can come to depend on dedicated and segregated neural tissue. In this paper, we describe a series of experiments that have investigated the neural development and organization of one such noninnate function: letter recognition. Functional neuroimaging demonstrates that letter and digit recognition depend on different neural substrates in some literate adults. How could the processing of two stimulus categories that are distinguished solely by cultural conventions become segregated in the brain? One possibility is that correlation-based learning in the brain leads to a spatial organization in cortex that reflects the temporal and spatial clustering of letters with letters in the environment. Simulations confirm that environmental co-occurrence does indeed lead to spatial localization in a neural network that uses correlation-based learning. Furthermore, behavioral studies confirm one critical prediction of this co-occurrence hypothesis, namely, that subjects exposed to a visual environment in which letters and digits occur together rather than separately (postal workers who process letters and digits together in Canadian postal codes) do indeed show less behavioral evidence for segregated letter and digit processing.

Population based randomised study of uptake and yield of screening by flexible sigmoidoscopy compared with screening by faecal occult blood testing

Objectives: To compare the feasibility of mass screening by flexible sigmoidoscopy with screening by faecal occult blood testing (Haemoccult) and both tests combined.

Which contacts of patients with meningococcal disease carry the pathogenic strain of Neisseria meningitidis? A population based study

Objectives: To determine the prevalence of the pathogenic strain of Neisseria meningitidis in contacts of patients with meningococcal disease, and to determine which contact groups are likely to be carriers and warrant chemoprophylaxis.

Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes

Human rhinoviruses, the most important etiologic agents of the common cold, are messenger-active single-stranded monocistronic RNA viruses that have evolved a highly complex cascade of proteolytic processing events to control viral gene expression and replication. Most maturation cleavages within the precursor polyprotein are mediated by rhinovirus 3C protease (or its immediate precursor, 3CD), a cysteine protease with a trypsin-like polypeptide fold. High-resolution crystal structures of the enzyme from three viral serotypes have been used for the design and elaboration of 3C protease inhibitors representing different structural and chemical classes. Inhibitors having α,β-unsaturated carbonyl groups combined with peptidyl-binding elements specific for 3C protease undergo a Michael reaction mediated by nucleophilic addition of the enzyme’s catalytic Cys-147, resulting in covalent-bond formation and irreversible inactivation of the viral protease. Direct inhibition of 3C proteolytic activity in virally infected cells treated with these compounds can be inferred from dose-dependent accumulations of viral precursor polyproteins as determined by SDS/PAGE analysis of radiolabeled proteins. Cocrystal-structure-assisted optimization of 3C-protease-directed Michael acceptors has yielded molecules having extremely rapid in vitro inactivation of the viral protease, potent antiviral activity against multiple rhinovirus serotypes and low cellular toxicity. Recently, one compound in this series, AG7088, has entered clinical trials.

Spatial localization of calcium channels in giant fiber lobe neurons of the squid (Loligo opalescens).

Whole-cell voltage clamp was used to investigate the properties and spatial distribution of fast-deactivating (FD) Ca channels in squid giant fiber lobe (GFL) neurons. Squid FD Ca channels are reversibly blocked by the spider toxin omega-Agatoxin IVA with an IC50 of 240-420 nM with no effect on the kinetics of Ca channel gating. Channels with very similar properties are expressed in both somatic and axonal domains of cultured GFL neurons, but FD Ca channel conductance density is higher in axonal bulbs than in cell bodies at all times in culture. Channels presumably synthesized during culture are preferentially expressed in the growing bulbs, but bulbar Ca conductance density remains constant while Na conductance density increases, suggesting that processes determining the densities of Ca and Na channels in this extrasomatic domain are largely independent. These observations suggest that growing axonal bulbs in cultured GFL neurons are not composed entirely of "axonal" membranes because FD Ca channels are absent from the giant axon in situ but, rather, suggest a potential role for FD Ca channels in mediating neurotransmitter release at the motor terminals of the giant axon.

Spatial heterogeneity of inhibitory surrounds in the middle temporal visual area.

A recurrent theme in the organization of vertebrate visual cortex is that of receptive fields with an associated "silent" opponency component. In the middle temporal area (area MT), a cortical visual area involved in the analysis of retinal motion in primates, this opponency appears in the form of a region outside the classical receptive field (CRF) that in itself gives no response but suppresses responses to motion evoked within the CRF. This antagonistic motion surround has been described as very large and symmetrically arrayed around the CRF. On the basis of this view, the primary function of the surround has long been thought to consist of simple figure-ground segregation based on movement. We have made use of small stimulus patches to map the form and extent of the surround and find evidence that the surround inhibition of many MT cells is in fact confined to restricted regions on one side or on opposite sides of the CRF. Such regions endow MT cells with the ability to make local-to-local motion comparisons, capable of extracting more complex features from the visual environment, and as such, may be better viewed as intrinsic parts of the receptive field, rather than as separate entities responsible for local-to-global comparisons.