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PubMed2004

Contribution of inhibitory mechanisms to direction selectivity and response normalization in macaque middle temporal area.

Inhibitory mechanisms contribute to directional tuning in primary visual cortex, and it has been suggested that, in the primate brain, the middle temporal area (MT) inherits most of its directional information from primary visual cortex (V1). To test the validity of this hierarchical scheme, we investigated whether directional tuning in MT was present upon blockade of local gamma-aminobutyratergic (GABAergic) inhibitory mechanisms. Direction selectivity during the initial 50 ms after response onset was abolished in many MT cells when the local inhibitory network was inactivated whereas direction selectivity in later response periods was largely unaffected. Thus, direction selectivity during early response periods is often generated autonomously within MT whereas direction selectivity during later response periods is either inherited from other visual areas or locally mediated by mechanisms other than gamma-aminobutyric acid type A receptor (GABA(A)) inhibition. GABAergic inhibition may also mediate contrast normalization. Our data suggest that GABA(A) inhibition implements a local direction-selective static nonlinearity, rather than a full normalization in MT. These findings put constraints on strict hierarchical models according to which MT performs more complex computations based on local motion measurements provided by earlier areas, arguing for more distributed and independent information processing.

Animals↗
PubMed2002

Early endosomes, late endosomes, and lysosomes display distinct partitioning strategies of inheritance with similarities to Golgi-derived membranes.

The pattern of inheritance of compartments of the endocytic pathway has been rarely reported, and the precise mechanism(s) are yet to be elucidated. We used antibodies reactive to early endosomes (anti-EEA1), late endosomes (anti-LBPA and anti-LAMP-1), lysosomes (anti-LAMP-1) and trans-Golgi network (TGN) (anti-GOLGA4) to examine the inheritance of these compartments in fixed human HEp-2 cells. Prior to entering M phase, these compartments display a perinuclear bias in their cytoplasmic distribution with areas of local accumulation juxtaposed to the centrosome. The location of these compartments during mitosis was examined relative to each other, the chromosomes, centrosomes and the microtubule network. During M phase early endosomes and TGN-derived compartments share overlapping subcellular distributions. A portion of these compartments display discernible clustering around the separated and migrating centrosomes in prophase. At metaphase these compartments co-localise with the mitotic spindle, are absent at the metaphase plate and do not overlay the astral microtubules. At anaphase these compartments are concentrated between shortening kinetochore microtubules and centrosomes. In addition, they appear distributed over the elongating polar microtubules in the body of the cell. From telophase and into cytokinesis these compartments concentrate around the minus ends of the constricted remnants of polar spindle microtubules and re-establish a prominent presence juxtaposed to the centrosome. In contrast, there is little evidence of movement of late endosomes and lysosomes with migrating centrosomes in prophase, and these compartments are excluded from the mitotic spindle at metaphase. However, by the end of telophase, the subcellular distribution of a portion of late endosomes and lysosomes share overlapping distributions with that of early endosomes. We conclude a portion of endosomal compartments and Golgi-derived membranes undergo ordered partitioning based on the centrosome and mitotic spindle.

Animals↗
PubMed1996

Optic flow processing in monkey STS: a theoretical and experimental approach.

How does the brain process visual information about self-motion? In monkey cortex, the analysis of visual motion is performed by successive areas specialized in different aspects of motion processing. Whereas neurons in the middle temporal (MT) area are direction-selective for local motion, neurons in the medial superior temporal (MST) area respond to motion patterns. A neural network model attempts to link these properties to the psychophysics of human heading detection from optic flow. It proposes that populations of neurons represent specific directions of heading. We quantitatively compared single-unit recordings in area MST with single-neuron simulations in this model. Predictions were derived from simulations and subsequently tested in recorded neurons. Neuronal activities depended on the position of the singular point in the optic flow. Best responses to opposing motions occurred for opposite locations of the singular point in the visual field. Excitation by one type of motion is paired with inhibition by the opposite motion. Activity maxima often occur for peripheral singular points. The averaged recorded shape of the response modulations is sigmoidal, which is in agreement with model predictions. We also tested whether the activity of the neuronal population in MST can represent the directions of heading in our stimuli. A simple least-mean-square minimization could retrieve the direction of heading from the neuronal activities with a precision of 4.3 degrees. Our results show good agreement between the proposed model and the neuronal responses in area MST and further support the hypothesis that area MST is involved in visual navigation.

Animals↗
PubMed1990

[Acute and chronic inflammatory reactions following implantation of artificial lenses].

Inflammatory reactions following IOL-implantation are being caused by different factors. A recent finding refers to the fact that bacteria of usually low pathogenity (i.e. Probionibacterium acnes, Staph. epidermidis, Staph. aureus haemolyticus) can enter the eye during implantation into the capsular bag and can cause an initially localized endophthalmitis. Previously this clinical appearance had frequently been mistaken as a "Toxic Lens Syndrome". Clinically, a persisting or increasing fibrin reaction with or without hypopyon, a typical whitish appearance of the capsule and a more or less marked vitreous infiltration up to a generalized endophthalmitis may be observed. For diagnostic purposes an isolation of germs from the fibrin network in the pupillary area or from the excised fragments of the capsular bag can be successful. Therapy of choice are locally applied antibiotics (i.e. the combination of Cephalosporin with Tobramycin) or eventually an operative intervention. If this is performed in the early course, the IOL can be saved in the majority of cases, although the visual acuity is usually reduced. Postoperative inflammatory reactions can also be caused by individual disposition (pseudoexfoliation, glaucoma, uveitis). No importance is being attributed furthermore to diagnoses like "Toxic Lens Syndrome" or "Pseudo-phako-anaphylactic Endophthalmitis'. Postoperative inflammatory reactions can be divided into five different clinical courses. In cases of bacterial contamination the prognosis is worsened by mono-steroid therapy.

Endophthalmitis↗
PubMed2005

Trends in speciated fine particulate matter and visibility across monitoring networks in the Southeastern United States.

Trends in fine particulate matter <2.5 microm in diameter (PM2.5) and visibility in the Southeastern United States were evaluated for sites in the Interagency Monitoring of Protected Visual Environments, Speciated Trends Network, and Southeastern Aerosol Research and Characterization Study networks. These analyses are part of the technical assessment by Visibility Improvement-State and Tribal Association of the Southeast (VISTAS), the regional planning organization for the southeastern states, in support of State Implementation Plans for the regional haze rule. At all of the VISTAS IMPROVE sites, ammonium sulfate and organic carbon (OC) are the largest and second largest contributors, respectively, to light extinction on both the 20% haziest and 20% clearest days. Ammonium nitrate, elemental carbon (EC), soils, and coarse particles make comparatively small contributions to PM2.5 mass and light extinction on most days at the Class I areas. At Southern Appalachian sites, the 20% haziest days occur primarily in the late spring to fall, whereas at coastal sites, the 20% haziest days can occur through out the year. Levels of ammonium sulfate in Class I areas are similar to those in nearby urban areas and are generally higher at the interior sites than the coastal sites. Concentrations of OC, ammonium nitrate, and, sometimes, EC, tend to be higher in the urban areas than in nearby Class I areas, although differences in measurement methods complicate comparisons between networks. Results support regional controls of sulfur dioxide for both regional haze and PM2.5 implementation and suggest that controls of local sources of OC, EC, or nitrogen oxides might also be considered for urban areas that are not attaining the annual National Ambient Air Quality Standard for PM2.5.

Air Pollution↗
PubMed1998

Distribution of nitric oxide synthase and nitric oxide-receptive, cyclic GMP-producing structures in the rat brain.

The structures capable of synthesizing cyclic GMP in response to nitric oxide in the rat brain were compared relative to the anatomical localization of neuronal nitric oxide synthase. In order to do this, we used brain slices incubated in vitro, where cyclic GMP-synthesis was stimulated using sodium nitroprusside as a nitric oxide-donor compound, in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine. Nitric oxide-stimulated cyclic GMP synthesis was found in cells and fibers, but was especially prominent in varicose fibers throughout the rat brain. Fibers containing the nitric oxide-stimulated cyclic GMP production were present in virtually every area of the rat brain although there were large regional variations in the density of the fiber networks. When compared with the localization of nitric oxide synthase, it was observed that although nitric oxide-responsive and the nitric oxide-producing structures were found in similar locations in general this distribution was complementary. Only occasionally was nitric oxide-mediated cyclic GMP synthesis observed in structures which also contained nitric oxide synthase. We conclude that the nitric oxide-responsive soluble guanylyl cyclase and nitric oxide synthase are usually juxtaposed at very short distances in the rat brain. These findings very strongly support the proposed role of nitric oxide as an endogenous activator of the soluble guanylyl cyclase in the central nervous system and convincingly demonstrate the presence of the nitric oxide-cyclic GMP signal transduction pathway in virtually every area of the rat brain.

1-Methyl-3-isobutylxanthine↗
PubMed1983

Intercellular junctions in hepatocellular carcinoma.

The freeze-fracture technique has been used to study the organization of intercellular junctions in two cases of hepatocellular carcinoma. A tumor free cirrhotic liver has been included for comparison. Tight junctions were disorganized in the tumor cells of hepatocellular carcinoma. The tight junction networks often were not orientated parallel to the canalicular lumen. In some areas tight junctions comprised 2 to 4 strands, while in other areas they were reduced to a single strand. Discontinuities and local proliferation of tight junctions were also seen. Some tight junctions were composed of intramembrane particles aligned to form a discontinuous network. Gap junctions between the tumor cells were small and infrequent. Gap junctions were found only on the lateral plasma membranes and were not seen within the tight junction networks. These findings have been interpreted to indicate changes in intercellular communication, and an alteration in the ability of hepatocytes to differentiate tight junctions in hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed2005

Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry.

Bipolar disorder (BD) has been associated with abnormalities of brain structure. Specifically, in vivo volumetric MRI and/or post mortem studies of BD have reported abnormalities of gray matter (GM) volume in the medial prefrontal cortex (PFC), amygdala, hippocampal subiculum and ventral striatum. These structures share anatomical connections with each other and form part of a "visceromotor" network modulating emotional behavior. Areas of the lateral orbital, superior temporal and posterior cingulate cortices project to this network, but morphometric abnormalities in these areas have not been established in BD. The current study assessed tissue volumes within these areas in BD using MRI and voxel-based morphometry (VBM). MRI images were obtained from 36 BD subjects and 65 healthy controls. To account for possible neurotrophic and neuroprotective effects of psychotropic medications, BD subjects were divided into medicated and unmedicated groups. Images were segmented into tissue compartments, which were examined on a voxel-wise basis to determine the location and extent of morphometric changes. The GM was reduced in the posterior cingulate/retrosplenial cortex and superior temporal gyrus of unmedicated BD subjects relative to medicated BD subjects and in the lateral orbital cortex of medicated BD subjects relative to controls. White matter (WM) was increased in the orbital and posterior cingulate cortices, which most likely reflected alterations in gyral morphology resulting from the reductions in the associated GM. The morphometric abnormalities in the posterior cingulate, superior temporal and lateral orbital cortices in BD support the hypothesis that the extended network of neuroanatomical structures subserving visceromotor regulation contains structural alterations in BD. Additionally, localization of morphometric abnormalities to areas known to exhibit increased metabolism in depression supports the hypothesis that repeated stress and elevated glucocorticoid secretion may result in neuroplastic changes in BD.

Adult↗
PubMed2001

Role of ethics committees, ethics networks, and ethics centers in improving end-of-life care.

This article chronicles the work of Midwest Bioethics Center, several community-state partnerships, and other local and national initiatives to determine their proper role and appropriate contribution. Professional education and development, institutional reform, and community engagement are areas of concern because ethics committees, networks, and centers sponsor workshops and conferences on palliative care for healthcare professionals, hold public forums, develop advance care planning projects, and provide expertise to legislators and other policymakers. The leading edge of the work being done by ethics committees, networks, and centers appears to be using continuous quality improvement methods, specifically the development of quality indicators, to promote accountability in end-of-life care reform efforts. This work is something that ethics committees can and should take on.

Journal Article↗
PubMed2006

Cortical network modeling: analytical methods for firing rates and some properties of networks of LIF neurons.

The circuitry of cortical networks involves interacting populations of excitatory (E) and inhibitory (I) neurons whose relationships are now known to a large extent. Inputs to E- and I-cells may have their origins in remote or local cortical areas. We consider a rudimentary model involving E- and I-cells. One of our goals is to test an analytic approach to finding firing rates in neural networks without using a diffusion approximation and to this end we consider in detail networks of excitatory neurons with leaky integrate-and-fire (LIF) dynamics. A simple measure of synchronization, denoted by S(q), where q is between 0 and 100 is introduced. Fully connected E-networks have a large tendency to become dominated by synchronously firing groups of cells, except when inputs are relatively weak. We observed random or asynchronous firing in such networks with diverse sets of parameter values. When such firing patterns were found, the analytical approach was often able to accurately predict average neuronal firing rates. We also considered several properties of E-E networks, distinguishing several kinds of firing pattern. Included were those with silences before or after periods of intense activity or with periodic synchronization. We investigated the occurrence of synchronized firing with respect to changes in the internal excitatory postsynaptic potential (EPSP) magnitude in a network of 100 neurons with fixed values of the remaining parameters. When the internal EPSP size was less than a certain value, synchronization was absent. The amount of synchronization then increased slowly as the EPSP amplitude increased until at a particular EPSP size the amount of synchronization abruptly increased, with S(5) attaining the maximum value of 100%. We also found network frequency transfer characteristics for various network sizes and found a linear dependence of firing frequency over wide ranges of the external afferent frequency, with non-linear effects at lower input frequencies. The theory may also be applied to sparsely connected networks, whose firing behaviour was found to change abruptly as the probability of a connection passed through a critical value. The analytical method was also found to be useful for a feed-forward excitatory network and a network of excitatory and inhibitory neurons.

Action Potentials↗
PubMed1998

Emulating the visual receptive-field properties of MST neurons with a template model of heading estimation.

We have proposed previously a computational neural-network model by which the complex patterns of retinal image motion generated during locomotion (optic flow) can be processed by specialized detectors acting as templates for specific instances of self-motion. The detectors in this template model respond to global optic flow by sampling image motion over a large portion of the visual field through networks of local motion sensors with properties similar to those of neurons found in the middle temporal (MT) area of primate extrastriate visual cortex. These detectors, arranged within cortical-like maps, were designed to extract self-translation (heading) and self-rotation, as well as the scene layout (relative distances) ahead of a moving observer. We then postulated that heading from optic flow is directly encoded by individual neurons acting as heading detectors within the medial superior temporal (MST) area. Others have questioned whether individual MST neurons can perform this function because some of their receptive-field properties seem inconsistent with this role. To resolve this issue, we systematically compared MST responses with those of detectors from two different configurations of the model under matched stimulus conditions. We found that the characteristic physiological properties of MST neurons can be explained by the template model. We conclude that MST neurons are well suited to support self-motion estimation via a direct encoding of heading and that the template model provides an explicit set of testable hypotheses that can guide future exploration of MST and adjacent areas within the superior temporal sulcus.

Head Movements↗
PubMed1996

VCAM-1 expression and network of VCAM-1 positive vascular dendritic cells in advanced atherosclerotic lesions of carotid arteries and aortas.

This study was undertaken to determine whether vascular dendritic cells (VDCs) display VCAM-1 in atherosclerotic lesions. Specimens of carotid artery and aorta were obtained at operation. All the plaques contained VCAM-1+ cells, but VCAM-1 immunoreactivity was irregularly distributed being mainly associated with the zones of neovascularisation in the base of the atherosclerotic plaques. Vascular dendritic cells were identified with DAKO-CD1 a. Alternative parallel sections were stained with either anti-CD1 a or anti-VCAM-1. By comparison of consecutive parallel sections the CD1a+ vascular dendritic cells were located separate from other intimal cells. In some areas networks formed by VCAM-1+ vascular dendritic cells were observed suggesting that cellular networks may mediate a local immune response in atherosclerotic lesions. We speculate that VCAM-1 is involved in the formation of cell-to-cell contacts of vascular dendritic cells in atherogenesis.

Adult↗
PubMed2006

Efficient estimation of graphlet frequency distributions in protein-protein interaction networks.

MOTIVATION: Algorithmic and modeling advances in the area of protein-protein interaction (PPI) network analysis could contribute to the understanding of biological processes. Local structure of networks can be measured by the frequency distribution of graphlets, small connected non-isomorphic induced subgraphs. This measure of local structure has been used to show that high-confidence PPI networks have local structure of geometric random graphs. Finding graphlets exhaustively in a large network is computationally intensive. More complete PPI networks, as well as PPI networks of higher organisms, will thus require efficient heuristic approaches. RESULTS: We propose two efficient and scalable heuristics for finding graphlets in high-confidence PPI networks. We show that both PPI and their model geometric random networks, have defined boundaries that are sparser than the 'inner parts' of the networks. In addition, these networks exhibit 'uniformity' of local structure inside the networks. Our first heuristic exploits these two structural properties of PPI and geometric random networks to find good estimates of graphlet frequency distributions in these networks up to 690 times faster than the exhaustive searches. Our second heuristic is a variant of a more standard sampling technique and it produces accurate approximate results up to 377 times faster than the exhaustive searches. We indicate how the combination of these approaches may result in an even better heuristic. AVAILABILITY: Supplementary information is available at http://www.cs.toronto.edu/~natasha/BIOINF-2005-0946/Supplementary.pdf. Software implementing the algorithms is available at http://www.cs.toronto.edu/~natasha/BIOINF-2005-0946/estimate_grap-hlets.html. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Algorithms↗
PubMed2007

Spatial bridges and the spread of Chlamydia: the case of a county in Sweden.

OBJECTIVES: The so-called small-world effect can have a great impact on efforts to control the incidence and prevalence of sexually transmitted infections. This is because a small number of so-called spatial bridgers (individuals who, through sexual contacts, interconnect geographically distant areas) can drastically lower the average path length in the sexual network and, as a result, make locally based intervention programs much less effective. The objectives of this study were to analyze the sociodemographic characteristics of these bridgers and to compare the result with the remaining study population. The purpose was to determine whether it is possible to identify them for targeted intervention programs. STUDY DESIGN: During 2001, contact tracing was performed in approximately 98% of all cases with positive test results in Värmland County. The sexual networks obtained constituted a study population of 851 individuals. Statistical analysis was used to characterize individuals engaged in spatial bridging behavior. RESULTS: Approximately 8% of the study population was characterized as spatial bridgers. Using multivariate analysis, we found almost no significant differences between these individuals and the rest of the study population when it came to sociodemographic variables, including education, economy, and ethnicity. CONCLUSION: The number of spatial bridgers is high enough to create a small-world network with links that can fuel the endemic chlamydia in Värmland County. Sociodemographic information could not be used to characterize spatial bridgers. In interventions against chlamydia, spatial bridgers shall be considered as potentially important for sustaining the disease.

Adolescent↗
PubMed1988

Deterioration of B cell proliferation correlates with dendritic reticulum cell destruction in germinal centers of an AIDS patient. Case study.

A lymph node from a bisexual Caucasian male infected with human immunodeficiency virus (HIV) and in the persistent generalized lymphadenopathy (PGL) stage was studied. Dendritic reticulum cells (DRCs) were well preserved in over half of the germinal centers (GCs), while in the rest, they showed marked destruction, producing patchy or rather wide DRC-depleted areas. Proliferation-associated antigens, i.e., PC antigen and DNA-polymerase alpha, were demonstrated in nuclei of germinal center B cells in areas where the DRC network was intact, while they were prominently depleted in areas where the DRC network was lost. The p-24 viral core antigen was shown to be localized in DRCs, especially those in the process of degeneration. These results suggest that the DRC in this patient, when infected with HIV, were destroyed, and that the resulting DRC depletion led to the suppression of B cell proliferation in GCs.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Neural correlates of auditory-visual stimulus onset asynchrony detection.

Intersensory temporal synchrony is an ubiquitous sensory attribute that has proven to be critical for binding multisensory inputs, sometimes erroneously leading to dramatic perceptual illusions. However, little is known about how the brain detects temporal synchrony between multimodal sensory inputs. We used positron emission tomography to demonstrate that detecting auditory-visual stimulus onset asynchrony activates a large-scale neural network of insular, posterior parietal, prefrontal, and cerebellar areas with the highest and task-specific activity localized to the right insula. Interregional covariance analysis further showed significant task-related functional interactions between the insula, the posterior thalamus, and superior colliculus. Based on these results and the available electrophysiological and anatomical connectivity data in animals, we propose that the insula, via its known short-latency connections with the tectal system, mediates temporally defined auditory-visual interaction at an early stage of cortical processing permitting phenomena such as the ventriloquist and the McGurk illusions.

Acoustic Stimulation↗
PubMed2002

Structural and energetic processes related to P300: LORETA findings in depression and effects of antidepressant drugs.

Noninvasive electrophysiological neuroimaging applied to cognitive components of event-related potentials (ERPs) may differentiate between structural and energetic processes related to information processing. The structural level, revealed by the location of the local maxima of the current source density distribution, describes the time-dependent network of activated brain areas. The magnitude of the source strength, a measure of the energetic component, describes the allocation of processing resources. ERPs were recorded in an odd-ball paradigm and low-resolution brain electromagnetic tomography (LORETA) was applied for standard and target ERP components. In a group of 60 menopausal depressed patients of 45-60 years of age, reduced P300 source strength was observed bilaterally, temporally and medially prefrontally reaching to rostal parts of the anterior cingulate, compared with 29 age-matched controls. In a double-blind, placebo-controlled study, 2 mg of the antidepressant citalopram induced a significant increase of P300 source strength in the (left) prefrontal cortex and precuneus compared with placebo, reaching to the posterior cingulate. Similar increases were observed after 800 mg S-adenosyl-L-methionine (SAMe) administered intravenously in ten young healthy subjects aged 22-33, and they were even more pronounced in ten elderly healthy subjects aged 56-71. Thus, ERP-tomography identified changes in energetic sources in brain areas predominantly involved in depression and in antidepressant action.

Acoustic Stimulation↗
PubMed1997

Hospital based primary care clinics. Complementary to general practice.

OBJECTIVE: To describe the patients attending a hospital based primary care clinic (HBPCC) focusing on the main medical and non-medical reasons for their seeking health care at the clinic, and their expectations of, and satisfaction with the care. METHODS: The study was set in a HBPCC in the northern region of metropolitan Melbourne, Australia. Bilingual interviewers assisted consecutive new patients to complete a pre- and post-consultation questionnaire seeking information on the presenting complaint, patient-reported reason for encounter (RFE), doctor-recorded health problem, treatments received, and patient expectations of and satisfaction with care. RESULTS: The sample (n = 197) was young (mean age 33 years). A high proportion came from a low socioeconomic group (68%) and there was a higher than expected proportion of patients with a non-English speaking background (NESB) (53%). Three-quarters had a regular GP elsewhere. Important reasons for choosing this service were accessibility and familiarity: being part of a hospital: case of obtaining radiological examinations, and the quality of the doctors. The commonest health problem was trauma related (14-16%). The main body systems involved were locomotor, skin, digestive, respiratory, pregnancy related and non specific. Patients were mostly satisfied with their cares those with ill-defined problems were more likely to report that their expectation were not completely met. There were no significant demographic and ethnic variations in the outcome variables. CONCLUSION: HBPCCs can complement the GP's ongoing relationship with patients from NESB and lower socioeconomic groups to improve the continuity and coordination of healthcare. Experienced and culturally sensitive GPs, good communications, and an effective and comprehensive interpreter service are necessary to facilitate this care coordination. One strategy is a hospital based department of general practice linking academic GPs and a local divisional network of GPs, to provide this clinical service and undertake teaching and research in the areas highlighted by this study.

Adult↗