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PubMed1988

Visual sensitivity to temporal change in focus and its relevance to the accommodation response.

Measurements were made of the ability of observers, whose accommodation had been paralysed, to detect the small changes in contrast resulting from sinusoidal, oscillatory changes in the dioptric focus of test objects, as a function of the mean position of focus. Variables studied included the form and wavelength composition of the test object, the diameter of the entrance pupil of the eye and the temporal frequency of the focus change. The dioptric amplitudes of the thresholds found (approximately 0.1 D) were comparable with the normally observed amplitudes of the microfluctuations of the accommodation system of the eye. A maximum for the threshold change of focus was found to occur about a mean position of focus corresponding to the nominal "best-focus". Two threshold minima occurred symmetrically on either side of this position of optimal mean focus; the positions of these minima depended on the spatial frequency content of the test object and the pupil diameter. The results are interpreted in terms of the corresponding through-focus changes in optical modulation transfer of the eye and data on the sensitivity of the visual system to spatial and temporal modulation. For sinusoidal grating test objects, it appears that the results can qualitatively be explained if it is assumed that the detectable focus change is such that the ratio of the modulation change in the retinal image, produced by the focus change, to the modulation at the mean position of focus is constant. Results for targets of broad spatial bandwidth suggest that sensitivity to focus change may be dominated by spatial frequency components approximately 5 c/deg. The implications of the data for the understanding of the accommodation control system are briefly considered.

Accommodation, Ocular↗

PubMed1988

Meridional anisotropies of orientation discrimination for sine wave gratings.

The difference limen for perceived stimulus orientation was measured for thin lines, and for sine wave gratings between 2.5 and 20.0 c/deg. All observers exhibited a marked meridional anisotropy on this task with both the thin line and grating test targets. For the sine wave gratings orientation discrimination was not found to depend on their spatial frequency. Contrast threshold measurements with the same set of stimuli confirmed earlier reports that the meridional anisotropy for contrast detection increases with test spatial frequency. The data are consistent with published hypotheses (Regan and Beverley, 1985) that detection and discrimination of spatial patterns may be processed differently by orientation selective elements of the visual system and that there are fewer of these mechanisms subserving oblique orientations than either vertical or horizontal orientations.

Discrimination, Psychological↗

PubMed1992

Texture segregation is processed by primary visual cortex in man and monkey. Evidence from VEP experiments.

We investigated whether the process of texture segregation can be allocated to a specific visual cortical area. We designed a stimulus to reveal the presence of a mechanism, which is specifically sensitive to a checkerboard, that is solely defined by textures segregating due to orientation differences of the constituting line segments. We recorded evoked potentials to this stimulus in man and awake monkey. A difference component, signalling texture segregation sensitivity, could be recorded from both types of subjects. Its presence depended on the spatial extent of the textures, in a manner correlating with the perceptibility of the checkerboard. This difference response could be localized in primary visual cortex by means of equivalent dipole estimations.

Animals↗

PubMed1996

Visual motion aftereffects: critical adaptation and test conditions.

The visual motion aftereffect (MAE) typically occurs when stationary contours are presented to a retinal region that has previously been exposed to motion. It can also be generated following observation of a stationary grating when two gratings (above and below it) move laterally: the surrounding gratings induce motion in the opposite direction in the central one. Following adaptation, the centre appears to move in the direction opposite to the previously induced motion, but little or no MAE is visible in the surround gratings [Swanston & Wade (1992) Perception, 21, 569-582]. The stimulus conditions that generate the MAE from induced motion were examined in five experiments. It was found that: the central MAE occurs when tested with stationary centre and surround gratings following adaptation to surround motion alone (Expt 1); no MAEs in either the centre or surround can be measured when the test stimulus is the centre alone or the surround alone (Expt 2); the maximum MAE in the central grating occurs when the same surround region is adapted and tested (Expt 3); the duration of the MAE is dependent upon the spatial frequency of the surround but not the centre (Expt 4); MAEs can be observed in the surround gratings when they are themselves surrounded by stationary gratings during test (Expt 5). It is concluded that the linear MAE occurs as a consequence of adapting restricted retinal regions to motion but it can only be expressed when nonadapted regions are also tested.

Adaptation, Ocular↗

PubMed1994

Transcription: in tune with the histones.

The regulation of transcription in eukaryotes relies upon the histone proteins in several essential ways. The incorporation of the binding sites for the basal transcriptional machinery into nucleosomes serves to repress transcription. Specific regulatory molecules other than the basal transcriptional machinery exist that can associate with nucleosomal DNA and initiate a chain of events that disrupt repressive histone-DNA complexes. The main players in this story have been defined physically and genetically and include positioned nucleosomes, interactions of the histone tetramer (H3-H4)2 with DNA, the N-terminal tails of histones H3 and H4, and a large general activator complex. How they fit together biochemically is yet to be defined. The genetic data demonstrate that the disruption of histone-DNA complexes plays a major role in the induction of transcription from many genes. However, not all genes are repressed by nucleosome assembly: certain promoters make use of the staged assembly of chromatin in vivo and a rapid and tight association of transacting factors with promoter elements to remain constitutively active. Moreover, nucleosome assembly is not necessarily repressive, since the folding of DNA by the histones can facilitate the activation of genes by bringing widely separated regulatory elements into juxtaposition. Thus, histones provide the necessary infrastructure for the correct and efficient operation of the transcriptional machinery; however, their exact contributions to the transcriptional regulation of an individual gene may depend on the spatial distribution of regulatory elements, the transcription factors involved, and the three-dimensional folding of DNA that they direct.

Histones↗

PubMed1987

Unilateral brain lesions in childhood: performance on the Revised Token Test.

Comprehension of connected language as assessed by the Revised Token Test (RTT) was studied in 17 children with left hemisphere lesions (LL) and 11 with right hemisphere lesions (RL). LL children's significantly lower performance on several subtests than left controls (LC) matched by age, sex, race, and social class appeared to be related to the memory demands of these subtests rather than the limited syntactic elements assessed by the RTT. LL subjects requested significantly more command repetitions than control or RL subjects and when a repetition was not requested LL subjects often responded with immediacy. Although RL children tended to perform lower than right matched controls (RC), these differences were not significant nor readily related to either the memory or specific linguistic structures assessed. RL subjects required fewer command repetitions than LL subjects and exhibited a significantly greater frequency of immediate responses than controls or LL subjects. While based on few children, a trend for LL children with retrorolandic lesions to perform more poorly than those with left prerolandic lesions was suggested. No systematic difference in performance was apparent for children with left cortical vs. left subcortical lesions or among discrete sites of lesions within the right hemisphere. Children with left lesions prior to 1 year of age performed no better and, in several instances, significantly poorer than LL patients sustaining lesions after 1 year of age. Among RL subjects, those sustaining lesions after 1 year of age had greater difficulty than those with lesion onset before 1 year of age, especially on linguistic elements which seemed to be dependent upon visual spatial properties. Further studies are needed to evaluate the comprehension of more complex linguistic structures among children with unilateral brain lesions as well as to study the role of more basic factors such as memory and attention in explaining the present findings.

Adolescent↗

PubMed1996

The differences shown by C57BL/6 and DBA/2 inbred mice in detecting spatial novelty are subserved by a different hippocampal and parietal cortex interplay.

Inbred C57BL/6 (C57) and DBA/2 (DBA) mice with hippocampus, posterior parietal cortex or sham lesions were placed in an open-field containing five objects and their reactivity to the displacement (spatial novelty) or the substitution (object novelty) of some of these objects was examined. C57 mice reacted to spatial novelty by exploring more the displaced than the non-displaced objects while DBA mice did not show any consistent reaction. In the highly reactive C57 strain, the peak of exploratory responses directed towards the displaced objects was completely abolished by hippocampal and posterior parietal cortex lesions. In the non-reactive DBA strain, hippocampal lesions induced an aspecific decreased interest towards the two categories of objects while posterior parietal cortex lesions did not produce any behavioral modification. The high reactivity of C57 mice to spatial change appears to be subserved by the conjunctive participation of the hippocampus and the posterior parietal cortex. Conversely, the deficit shown by DBA mice in that situation seems to be related to: (i) a poorly functional hippocampus; and (ii) the non-involvement of the posterior parietal cortes. The present data suggest that the participation of the posterior parietal cortes to the detection of spatial novelty may depend on the degree of functionality of the hippocampus.

Animals↗

PubMed1992

Microdosimetric measurements of heavy ion tracks.

The biological effectiveness of radiations depends on the spatial pattern of ionizations and excitations produced by the charged particle tracks involved. Ionizations produced by both the primary ion and by energetic delta rays may contribute to the production of biologically relevant damage and to the concentration of damage which may effect the probability of repair. Although average energy concentration (dose) can be calculated using homogeneous track models, the energy is actually concentrated in small volumes containing segments of the ion and delta ray tracks. These local concentrations are studied experimentally using low pressure proportional counters, and theoretically, using Monte Carlo methods. Small volumes near an ion track may be traversed by a delta ray. If they are, the energy deposited will be similar to that produced by a single electron track in a low-energy x-ray irradiation. The probability of a delta ray interaction occurring decreases with the square of the radial distance from the track. The average energy deposited is the product of this probability and the energy deposited in an interaction. Average energy deposited calculated from measured interaction probability is in good agreement with the results of homogeneous track models.

Computer Simulation↗

PubMed1994

Desmosomal cadherins: another growing multigene family of adhesion molecules.

The formation of supracellular structures, i.e. tissues and organs, is dependent on the spatially and temporally regulated formation of semistable cell-cell contacts. In recent years, the molecular components of such cell junctions, especially those occurring in epithelial cells, have been studied extensively, and the main proteins and glycoproteins of the 'adhering junctions' such as the desmosomes and the zonula adherens of polar epithelial cells have been characterized. We are now beginning to understand the complex protein-protein interactions that contribute to the assembly and disassembly of these structures and their roles in the attachment of specific filaments of the cytoskeleton.

Animals↗

PubMed1990

Receptor tyrosine kinases mediate cell-cell interactions during Drosophila development.

In vertebrates, receptor tyrosine kinases (RTKs) have been identified as growth factor receptors and proto-oncogenes. Many of these RTKs appear to play a key role in the regulation of cell growth. Recent analyses of several Drosophila genes encoding putative RTKs indicate that this class of proteins also serves an important role in cell fate decisions which depend on cellular interactions during development. The sevenless RTK mediates the position-dependent specification of a particular photoreceptor cell type (R7) in the eye. The local specification of R7 cells requires a functional tyrosine kinase domain of the sevenless protein but does not depend on the spatially restricted expression of the sevenless gene. The Drosophila EGF receptor homolog serves multiple functions during development, some of which are clearly unrelated to regulation of cell growth. Finally, the torso gene encodes an RTK required for the specification of the terminal regions of the Drosophila larva. A number of other genes have been genetically identified that appear to function in the same developmental processes upstream or downstream of these three RTKs. These loci are excellent candidates for genes encoding other components of the signalling pathways such as ligands or substrates of the RTKs.

Animals↗

PubMed2004

Light-induced excitation energy redistribution in Spirulina platensis cells: "spillover" or "mobile PBSs"?

State transitions induced by light and redox were investigated by observing the 77 K fluorescence spectra for the intact cells of Spirulina platensis. To clarify if phycobilisomes (PBSs) take part in the state transition, the contributions of PBSs to light-induced state transition were studied in untreated cells and the cells treated by betaine which fixed PBSs firmly on the thylakoid membranes. It was observed that the betaine-treated cells did not show any light-induced state transition. This result definitely confirmed that the light-induced excitation energy regulation between the two photosystems is mainly dependent on a spatial movement of PBSs on the thylakoid membranes, which makes PBS cores partially decoupled from photosystem II (PSII) while PBS rods more strongly coupled with photosystem I (PSI) during the transition from state 1 to state 2. On the other hand, an energy exchange between the two photosystems was observed in both untreated and betaine-treated cells during redox-induced state transition. These observations suggested that two different mechanisms were involved in the light-induced state transition and the redox-induced one. The former involves only a physical movement of PBSs, while the latter involves not only the movement of PBS but also energy spillover from PSII to PSI. A model for light-induced state transition was proposed based on the current results as well as well known knowledge.

Betaine↗

PubMed2006

Longitudinal study of the effects of a high-fat diet on glucose regulation, hippocampal function, and cerebral insulin sensitivity in C57BL/6 mice.

Although the increasing rate of obesity has stimulated interest in the effects of diet composition on peripheral systems, comparatively little work has been done to examine effects upon the brain. A diet high in fat is one of many factors that can promote obesity, and previous research has shown that such a diet can produce learning and memory impairment in rodents. In the present study, C57BL/6 mice were placed on either a high-fat (45% kcal fat) or regular (5% kcal fat) diet, and examined at different points during the subsequent year. The high-fat diet led to increased weight gain, significant impairment in glucoregulation, and altered insulin-mediated signaling within the hippocampus, an area of the brain believed to be important for the acquisition of memory. Following ten months on either diet, synaptic function in ex vivo hippocampal slices was examined, and neither stimulus-response curves nor electrically induced long-term potentiation were found to be different. As well, performance in the Morris water maze, a hippocampal-dependent test of spatial memory, was not influenced by diet. However, mice consuming a high-fat diet failed to perform an operant bar-pressing task, indicating a significant impairment to procedural learning and consolidation processes. Despite causing broad peripheral changes in C57BL/6 mice, consuming a large proportion of calories from saturated fat had only a limited effect upon learning and memory, which suggests that certain aspects of brain function are selectively vulnerable to the influences of diet.

Analysis of Variance↗

PubMed2004

Effect of intermittent hypoxia on long-term potentiation in rat hippocampal slices.

Intermittent hypoxia (IH) during sleep has been shown to induce apoptosis in a time-dependent manner and spatial learning deficits in adult rats. Recently, we have demonstrated that IH induced significant decreases in Ser-133-phosphorylated cAMP-response element-binding protein (pCREB) without changes in total CREB. The expression of cleaved caspase 3 in the hippocampal CA1, a marker of apoptosis, peaked at 3 days of IH and returned to normoxic values at 14 days of IH. In addition, biphasic changes in spatial task learning were correlated with the CREB phosphorylation time course. In the present study, the rat hippocampal slice preparation was used to evaluate the ability to induce and maintain a CA1 population spike long-term potentiation (PS-LTP) in room air (RA)-maintained and IH-exposed rats. A significant decrease in the ability to sustain PS-LTP for 15 min in slices prepared from IH-exposed rats for either 3 days (34% of total) or 7 days (51% of total) as compared to slices prepared from RA-maintained rats (76% of total) was observed. These results suggest that the diminishment in the ability of neuronal tissue to express and sustain PS-LTP is correlated with previously reported biphasic changes in CREB phosphorylation and programmed cell death.

Action Potentials↗

PubMed2006

Texture analysis of ultrasonic images of symptomatic carotid plaques can identify those plaques associated with ipsilateral embolic brain infarction.

OBJECTIVES: The aim of our study was to determine the association between objective, computerised texture analysis of carotid plaque ultrasonic images and embolic CT-brain infarction in patients presenting with hemispheric neurological symptoms. DESIGN: Cross-sectional study in patients with 50%-99% (ECST) carotid stenosis. PATIENTS AND METHODS: Carotid plaque ultrasonic images (n=54, 26 with TIAs and 28 with stroke) obtained during carotid ultrasound were normalised and standardised for resolution and subsequently assessed visually for the presence of discrete echogenic or juxtaluminal echolucent components and overall echogenicity (plaque type). Using computer software, 51 histogram/textural features of the plaque outlines were calculated. Factor analysis was subsequently applied to eliminate redundant variables. Small cortical, large cortical and discrete subcortical infarcts on CT-brain scan were considered as being embolic. RESULTS: Twenty-five cases (46%) had embolic infarcts. On logistic regression, grey-scale median (GSM), a measure of echolucency, spatial grey level dependence matrices (SGLDM) correlation and SGLDM information measure of correlation-1, measures of homogeneity were significant (p<0.05), but not grey level runlength statistics (RUNL) Run Percentage (RP), stenosis severity, type of symptoms or echolucent juxtaluminal components. Using ROC curves methodology, SGLDM information measure of correlation-1 improved the value of GSM in distinguishing embolic from non-embolic CT-brain infarction. CONCLUSION: Computerised texture analysis of ultrasonic images of symptomatic carotid plaques can identify those that are associated with brain infarction, improving the results achieved by GSM alone. This methodology could be applied to prospective natural history studies of symptomatic patients not operated on or randomised trials of patients undergoing carotid angioplasty and stenting in order to identify high-risk subgroups for cerebral infarction.

Algorithms↗

PubMed2006

Alterations in hippocampal neurogenesis following traumatic brain injury in mice.

Clinical and experimental data show that traumatic brain injury (TBI)-induced cognitive changes are often manifest as deficits in hippocampal-dependent functions of spatial information processing. The underlying mechanisms for these effects have remained elusive, although recent studies have suggested that the changes in neuronal precursor cells in the dentate subgranular zone (SGZ) of the hippocampus might be involved. Here, we assessed the effects of unilateral controlled cortical impact on neurogenic cell populations in the SGZ in 2-month-old male C57BL6 mice by quantifying numbers of dying cells (TUNEL), proliferating cells (Ki-67) and immature neurons (Doublecortin, Dcx) up to 14 days after TBI. Dying cells were seen 6 h after injury, peaked at 24 h and returned to control levels at 14 days. Proliferating cells were decreased on the ipsilateral and contralateral sides at all the time points studied except 48 h after injury when a transient increase was seen. Simultaneously, immature neurons were reduced up to 84% relative to controls on the ipsilateral side. In the first week post-TBI, reduced numbers of Dcx-positive cells were also seen in the contralateral side; a return to control levels occurred at 14 days. To determine if these changes translated into longer-term effects, BrdU was administered 1 week post-injury and 3 weeks later the phenotypes of the newly born cells were assessed. TBI induced decreases in the numbers of BrdU-positive cells and new neurons (BrdU/NeuN) on the ipsilateral side without apparent changes on the contralateral side, whereas astrocytes (BrdU/GFAP) were increased on the ipsilateral side and activated microglia (BrdU/CD68) were increased on both ipsi- and contralateral sides. No differences were noted in oligodendrocytes (BrdU/NG2). Taken together, these data demonstrate that TBI alters both neurogenesis and gliogenesis. Such alterations may play a contributory role in TBI-induced cognitive impairment.

Animals↗

PubMed2005

Endothelial cell activation of the smooth muscle cell phosphoinositide 3-kinase/Akt pathway promotes differentiation.

OBJECTIVE: Interactions between endothelial cells (ECs) and smooth muscle cells (SMCs) are fundamental in diverse cardiovascular processes such as arteriogenesis, atherosclerosis, and restenosis. We aimed to determine the intracellular signaling mechanisms by which ECs promote a differentiated SMC phenotype. METHODS: Bovine thoracic aorta ECs and SMCs were isolated and cultured. For co-culture studies, ECs were grown to confluence on one side of a semi-permeable Cyclopore membrane. SMCs were then plated on the opposite side of the membrane and cultured for 24 to 48 hours. For adenovirus experiments, SMCs were infected prior to plating opposite ECs. For conditioned media studies, SMCs cultured alone on plastic were treated with media harvested from EC/SMC in co-culture. SMC phenotype was assayed by microscopy and measurement of two-dimensional area, or by western blotting for contractile protein markers of differentiation. Akt activation was measured by western blotting for phospho-Serine 473. RESULTS: Although SMCs cultured alone exhibit a dedifferentiated synthetic phenotype, we report that bilayer co-culture with ECs induced a differentiated SMC phenotype as measured by morphology and cell area and expression of protein markers of differentiation, including contractile proteins and the cyclin-dependent kinase inhibitor p27 kip . The EC/SMC bilayer co-culture resulted in activation of the SMC protein kinase Akt, with no effect on total Akt expression. Similarly, conditioned media from co-cultured EC/SMC promoted rapid Akt phosphorylation and subsequent expression of differentiation protein markers in SMCs cultured alone. Adenoviral overexpression of constitutively active Akt in SMCs cultured alone mimicked the ability of ECs to induce SMC differentiation. Notably, inhibition of phosphoinositide 3 (PI 3)-kinase activity with wortmannin or adenoviral overexpression of a dominant-negative Akt prevented the EC-mediated effect on SMC morphology and differentiation protein marker expression. CONCLUSIONS: ECs direct SMCs towards a differentiated phenotype through activation of the SMC PI 3-kinase/Akt pathway. CLINICAL RELEVANCE: Interactions between endothelial cells (ECs) and smooth muscle cells (SMCs) are fundamental in diverse cardiovascular processes such as arteriogenesis, collateral blood vessel development, atherosclerosis, and restenosis. Alterations in SMC phenotype occur in each of these processes. Endothelial denudation has been suggested to contribute to the SMC proliferative response to vessel injury by angioplasty or other catheterization procedures. We have employed a co-culture approach to dissect the molecular signals that are dependent on the spatial relationship between ECs and SMCs, and have identified the importance of the PI3K/Akt pathway in EC-induced SMC differentiation. This pathway may suggest targets for therapeutic interventions for intimal hyperplasia and restenosis.

Animals↗

PubMed2005

Analyses of murine postsynaptic density-95 identify novel isoforms and potential translational control elements.

Postsynaptic density-95 (PSD-95) is an evolutionarily conserved synaptic adaptor protein that is known to bind many proteins including the NMDA receptor. This observation has implicated it in many NMDA receptor-dependent processes including spatial learning and synaptic plasticity. We have cloned and characterised the murine PSD-95 gene. In addition, we have identified two previously uncharacterised splice variants of the major murine PSD-95 transcript (PSD-95alpha): PSD-95alpha-2b results from an extension of exon 2 and PSD-95alpha-Delta18 from the temporal exclusion of exon 18. The presence of PSD-95alpha-2b sequences in other PSD-95 family members implicates this peptide stretch as functionally significant. Another potential transcript (PSD-95gamma) was also identified based on examination of EST databases. Immunoprecipitation assays demonstrate that proteins corresponding in size to PSD-95alpha-Delta18 and PSD-95gamma interact with the NMDA receptor, suggesting an important biological role for these isoforms. Finally, we have performed bioinformatics analyses of the PSD-95 mRNA untranslated regions, identifying multiple translational control elements that suggest protein production could be regulated post-transcriptionally. The variety of mRNA isoforms and regulatory elements identified provides for a high degree of diversity in the structure and function of PSD-95 proteins.

Age Factors↗

PubMed2026

A systematic review and meta-analysis of visuospatial attentional deficits in Parkinson's patients.

Parkinson's disease (PD) is a neurodegenerative condition primarily characterized by motor deficits, yet cognitive impairments are increasingly recognized. While deficits in executive functioning are well documented even in the absence of cognitive decline, evidence of attentional deficits in PD remains inconsistent, and the role of motor symptom lateralization is unclear. In this systematic review and meta-analysis, we examined visual attention in right-handed, cognitively unimpaired idiopathic PD patients, focusing on the canonical attentional domains (sustained, selective, divided) and processes (alerting, endogenous and exogenous orienting, reorienting), as well as visuospatial bias. Four databases were searched for studies comparing PD patients with healthy controls. Meta-analytic estimates were derived using Hedges' g within random-effects models, and studies that could not be quantitatively integrated were summarized narratively. In addition, studies directly comparing patients with left- and right-predominant motor symptoms (LPD vs. RPD) were reviewed qualitatively. Across 51 studies, PD patients exhibited deficits in sustained, selective, and divided attention. Among attentional processes, only exogenous orienting was impaired, whereas alerting, endogenous orienting, and reorienting were preserved. Findings from the few studies examining visuospatial bias indicated small, context-dependent shifts in spatial attention rather than a consistent directional bias. These findings indicate that PD patients show visual-attentional impairments, particularly under high-demand conditions, while basic alertness and voluntary orienting appear preserved. Exogenous orienting deficits and subtle rightward spatial tendencies in LPD suggest disruption of right-hemisphere attentional networks. These results have implications for early cognitive assessment, rehabilitation strategies, and understanding the neural bases of attentional dysfunction in PD.

Humans↗