The V-ATPase in Paramecium:functional specialization by multiple gene isoforms

The vacuolar H(+)-ATPase (V-ATPase), a multisubunit, adenosine triphosphate (ATP)-driven proton pump, is essential for numerous cellular processes in all eukaryotes investigated so far. While structure and catalytic mechanism are similar to the evolutionarily related F-type ATPases, the V-ATPase's main function is to establish an electrochemical proton potential across membranes using ATP hydrolysis. The holoenzyme is formed by two subcomplexes, the transmembraneous V(0) and the cytoplasmic V(1) complexes. Sequencing of the whole genome of the ciliate Paramecium tetraurelia enabled the identification of virtually all the genes encoding V-ATPase subunits in this organism and the studying of the localization of the enzyme and roles in membrane trafficking and osmoregulation. Surprisingly, the number of V-ATPase genes in this free-living protozoan is strikingly higher than in any other species previously studied. Especially abundant are V(0)-a-subunits with as many as 17 encoding genes. This abundance creates the possibility of forming a large number of different V-ATPase holoenzymes by combination and has functional consequences by differential targeting to various organelles.

Optic flow in human vision: MEG reveals a foveo-fugal bias in V1, specialization for spiral space in hMSTs, and global motion sensitivity in the IPS

Abstract We recorded MEG responses from 17 participants viewing random-dot patterns simulating global optic flow components (expansion, contraction, rotation, deformation, and translation) and a random motion control condition. Theta-band (3–7 Hz), MEG signal power was greater for expansion than the other optic flow components in a region concentrated along the calcarine sulcus, indicating an ecologically valid, foveo-fugal bias for unidirectional motion sensors in V1. When the responses to the optic flow components were combined, a decrease in MEG beta-band (17–23 Hz) power was found in regions extending beyond the calcarine sulcus to the posterior parietal lobe (inferior to IPS), indicating the importance of structured motion in this region. However, only one cortical area, within or near the V5/hMT+ complex, responded to all three spiral-space components (expansion, contraction, and rotation) and showed no selectivity for global translation or deformation: we term this area hMSTs. This is the first demonstration of an exclusive region for spiral space in the human brain and suggests a functional role better suited to preliminary analysis of ego-motion than surface pose, which would involve deformation. We also observed that the rotation condition activated the cerebellum, suggesting its involvement in visually mediated control of postural adjustment.

Topography of the visual evoked magnetic response and hemispherical specialization

The visual evoked magnetic response CIIm component to a pattern onset stimulus presented half field produced a consistent scalp topography in 15 normal subjects. The major response was seen over the contralateral hemisphere, suggesting a dipole with current flowing away from the medial surface of the brain. Full field responses were more unpredictable. The reponses of five subjects were studied to the onset of a full, left half and right half checkerboard stimuli of 38 x 27 min arc checks appearing for 200 ms. In two subjects the full field CIIm topography was consistent with that of the mathematical summation of their relevant half field distribution. The remaining subjects had unpredictable full field topographies, showing little or no relationship to their half or summated half fields. In each of these subjects, a distribution matching that of the summated half field CIIm distribution appears at an earlier latency than that of the predominant full field waveform peak. By examining the topography of the full and half field responses at 5 ms intervals along the waveform for one such subject, the CIIm topography of the right hemisphere develops 10 ms before that of the left hemisphere, and is replaced by the following CIIIm component 20 ms earlier. Hence, the large peak seen in full field results from a combination of the CIIm component of the left hemisphere plus that of the CIIIm from the right. The earlier peak results from the CIIm generated in both hemispheres, at a latency where both show similar amplitudes. As the relative amplitudes of these two peaks alter with check and field size, topographic studies would be required for accurate CIIm identification. In addition. the CIIm-CIIIm complex lasts for 80 ms in the right hemisphere and 135 ms in the left, suggesting hemispherical apecialization in the visual processing of the pattern onset response.

Differential impact of posterior lesions in the left and right hemisphere on visual category learning and generalization to contrast reversal

Hemispheric differences in the learning and generalization of pattern categories were explored in two experiments involving sixteen patients with unilateral posterior, cerebral lesions in the left (LH) or right (RH) hemisphere. In each experiment participants were first trained to criterion in a supervised learning paradigm to categorize a set of patterns that either consisted of simple geometric forms (Experiment 1) or unfamiliar grey-level images (Experiment 2). They were then tested for their ability to generalize acquired categorical knowledge to contrast-reversed versions of the learning patterns. The results showed that RH lesions impeded category learning of unfamiliar grey-level images more severely than LH lesions, whereas this relationship appeared reversed for categories defined by simple geometric forms. With regard to generalization to contrast reversal, categorization performance of LH and RH patients was unaffected in the case of simple geometric forms. However, generalization to of contrast-reversed grey-level images distinctly deteriorated for patients with LH lesions relative to those with RH lesions, with the latter (but not the former) being consistently unable to identify the pattern manipulation. These findings suggest a differential use of contrast information in the representation of pattern categories in the two hemispheres. Such specialization appears in line with previous distinctions between a predominantly lefthemispheric, abstract-analytical and a righthemispheric, specific-holistic representation of object categories, and their prediction of a mandatory representation of contrast polarity in the RH. Some implications for the well-established dissociation of visual disorders for the recognition of faces and letters are discussed.

A psychological investigation into the relationship between hemispheric functioning and specific written language difficulties (dyslexia), using pharmaceutical intervention techniques

This thesis attempts a psychological investigation of hemispheric functioning in developmental dyslexia. Previous work using neuropsychological methods with developmental dyslexics is reviewed ,and original work is presented both of a conventional psychometric nature and also utilising a new means of intervention. At the inception of inquiry into dyslexia, comparisons were drawn between developmental dyslexia and acquired alexia, promoting a model of brain damage as the common cause. Subsequent investigators found developmental dyslexics to be neurologically intact, and so an alternative hypothesis was offered, namely that language is abnormally localized (not in the left hemisphere). Research in the last decade, using the advanced techniques of modern neuropsychology, has indicated that developmental dyslexics are probably left hemisphere dominant for language. The development of a new type of pharmaceutical prep~ration (that appears to have a left hemisphere effect) offers an oppertunity to test the experimental hypothesis. This hypothesis propounds that most dyslexics are left hemisphere language dominant, but some of these language related operations are dysfunctioning. The methods utilised are those of psychological assessment of cognitive function, both in a traditional psychometric situation, and with a new form of intervention (Piracetam). The information resulting from intervention will be judged on its therapeutic validity and contribution to the understanding of hemispheric functioning in dyslexics. The experimental studies using conventional psychometric evaluation revealed a dyslexic profile of poor sequencing and name coding ability, with adequate spatial and verbal reasoning skills. Neuropsychological information would tend to suggest that this profile was indicative of adequate right hemsiphere abilities and deficits in some left hemsiphere abilities. When an intervention agent (Piracetam) was used with young adult dyslexics there were improvements in both the rate of acquisition and conservation of verbal learning. An experimental study with dyslexic children revealed that Piracetam appeared to improve reading, writing and sequencing, but did not influence spatial abilities. This would seem to concord with other recent findings, that deve~mental dyslexics may have left hemisphere language localisation, although some of these language related abilities are dysfunctioning.

Do left and right asymmetries of hemispheric preference interact with attention to predict local and global performance in applied tasks?

Many cognitive neuroscience studies show that the ability to attend to and identify global or local information is lateralised between the two hemispheres in the human brain; the left hemisphere is biased towards the local level, whereas the right hemisphere is biased towards the global level. Results of two studies show attention-focused people with a right ear preference (biased towards the left hemisphere) are better at local tasks, whereas people with a left ear preference (biased towards the right hemisphere) are better at more global tasks. In a third study we determined if right hemisphere-biased followers who attend to global stimuli are likely to have a stronger relationship between attention and globally based supervisor ratings of performance. Results provide evidence in support of this hypothesis. Our research supports our model and suggests that the interaction between attention and lateral preference is an important and novel predictor of work-related outcomes. © 2012 Copyright Psychology Press Ltd.

Seventeen a-subunit isoforms of paramecium V-ATPase provide high specialization in localization and function

In the Paramecium tetraurelia genome, 17 genes encoding the 100-kDa-subunit (a-subunit) of the vacuolar-proton-ATPase were identified, representing by far the largest number of a-subunit genes encountered in any organism investigated so far. They group into nine clusters, eight pairs with >82% amino acid identity and one single gene. Green fluorescent protein-tagging of representatives of the nine clusters revealed highly specific targeting to at least seven different compartments, among them dense core secretory vesicles (trichocysts), the contractile vacuole complex, and phagosomes. RNA interference for two pairs confirmed their functional specialization in their target compartments: silencing of the trichocyst-specific form affected this secretory pathway, whereas silencing of the contractile vacuole complex-specific form altered organelle structure and functioning. The construction of chimeras between selected a-subunits surprisingly revealed the targeting signal to be located in the C terminus of the protein, in contrast with the N-terminal targeting signal of the a-subunit in yeast. Interestingly, some chimeras provoked deleterious effects, locally in their target compartment, or remotely, in the compartment whose specific a-subunit N terminus was used in the chimera.

GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson's disease

In Parkinson's disease (PD), elevated beta (15-35Hz) power in subcortical motor networks is widely believed to promote aspects of PD symptomatology, moreover, a reduction in beta power and coherence accompanies symptomatic improvement following effective treatment with l-DOPA. Previous studies have reported symptomatic improvements that correlate with changes in cortical network activity following GABAA receptor modulation. In this study we have used whole-head magnetoencephalography to characterize neuronal network activity, at rest and during visually cued finger abductions, in unilaterally symptomatic PD and age-matched control participants. Recordings were then repeated following administration of sub-sedative doses of the hypnotic drug zolpidem (0.05mg/kg), which binds to the benzodiazepine site of the GABAA receptor. A beamforming based 'virtual electrode' approach was used to reconstruct oscillatory power in the primary motor cortex (M1), contralateral and ipsilateral to symptom presentation in PD patients or dominant hand in control participants. In PD patients, contralateral M1 showed significantly greater beta power than ipsilateral M1. Following zolpidem administration contralateral beta power was significantly reduced while ipsilateral beta power was significantly increased resulting in a hemispheric power ratio that approached parity. Furthermore, there was highly significant correlation between hemispheric beta power ratio and Unified Parkinson's Disease Rating Scale (UPDRS). The changes in contralateral and ipsilateral beta power were reflected in pre-movement beta desynchronization and the late post-movement beta rebound. However, the absolute level of movement-related beta desynchronization was not altered. These results show that low-dose zolpidem not only reduces contralateral beta but also increases ipsilateral beta, while rebalancing the dynamic range of M1 network oscillations between the two hemispheres. These changes appear to underlie the symptomatic improvements afforded by low-dose zolpidem.