The visually evoked magnetic response (VEMR) to a pattern onset/offset stimulus

This study characterizes the visually evoked magnetic response (VEMR) to pattern onset/offset stimuli, using a single channel BTi magnetometer. The influence of stimulus parameters and recording protocols on the VEMR is studied with inferences drawn about the nature of cortical processing, its origins and optimal recording strategies. Fundamental characteristics are examined, such as the behaviour of successive averaged and unaveraged responses; the effects of environmental shielding; averaging; inter- and intrasubject variability and equipment specificity. The effects of varying check size, field size, contrast and refractive error on latency, amplitude and topographic distribution are also presented. Latency and amplitude trends are consistent with previous VEP findings and known anatomical properties of the visual system. Topographic results are consistent with the activity of sources organised according to the cruciform model of striate cortex. A striate origin for the VEMR is also suggested by the results to quarter, octant and annulus field stimuli. Similarities in the behaviour and origins of the sources contributing to the CIIm and CIIIm onset peaks are presented for a number of stimulus conditions. This would be consistent with differing processing event in the same, or similar neuronal populations. Focal field stimuli produce less predictable responses than full or half fields, attributable to a reduced signal to noise ratio and an increased sensitivity to variations in cortical morphology. Problems with waveform peak identification are encountered for full field stimuli that can only be resolved by the careful choice of stimulus parameters, comparisons with half field responses or with reference to the topographic distribution of each waveform peak. An anatomical study of occipital lobe morphology revealed large inter- and intrasubject variation in calcarine fissure shape and striate cortex distribution. An appreciation of such variability is important for VEMR interpretation, due to the technique's sensitivity to source depth and orientation, and it is used to explain the experimental results obtained.

Spatial tuning studies of the pattern evoked electroretinogram

The locus of origin of the pattern evoked electroretinogram, (PERG), has been the subject of considerable discussion. A novel approach was adopted in this study to further elaborate the nature of the PERG evoked by pattern onset/offset presentation. The PERG was found to be linearly related to stimulus contrast and in particular was linearly related to the temporal contrast of the retinal image, when elicited by patterns of low spatial frequency. At high spatial frequencies the retinal image contrast is significantly reduced because of optical degradation. This is described by the eye's modulation transfer function (MTF). The retinal contrast of square wave grating and chequerboard patterns of increasing spatial frequency were found by filtering their Fourier transforms by the MTF. The filtered pattern harmonics were then resynthesised to constitute a profile of retinal image illuminance from which the temporal and spatial contrast of the image could be calculated. If the PERG is a pure illuminance response it should be spatially insensitive and dependent upon the temporal contrast of stimulation. The calculated loss of temporal contrast for finer patterns was expressed as a space-averaged temporal contrast attentuation factor. This factor, applied to PERGs evoked by low spatial frequency patterns, was used to predict the retinal illuminance response elicited by a finer pattern. The predicted response was subtracted from the recorded signal and residual waveform was proposed to represent specific activity. An additional correction for the attenuation of spatial contrast was applied to the extracted pattern specific response. Pattern specific responses computed for different spatial frequency patterns in this way are the predicted result of iso-contrast pattern stimulation. The pattern specific responses demonstrate a striking bandpass spatial selectivity which peaks at higher spatial frequencies in the more central retina. The variation of spatial sensitivity with eccentricity corresponds closely with estimated ganglion receptive field centre separation and psychophysical data. The variation of retinal structure with eccentricity, in the form of the volumes of the nuclear layers, was compared with the amplitudes of the computed retinal illuminance and pattern specific responses. The retinal illuminance response corresponds more closely to the outer and inner nuclear layers whilst the pattern specific response appears more closely related to the ganglion cell layer. In general the negative response transients correspond to the more proximal retinal layers. This thesis therefore supports the proposed contribution of proximal retinal cell activity to the PERG and describes techniques which may be further elaborated for more detailed studies of retinal receptive field dimensions.

A penny for your thoughts! Patterns of fMRI activity reveal the content and the spatial topography of visual mental images

Visual mental imagery is a complex process that may be influenced by the content of mental images. Neuropsychological evidence from patients with hemineglect suggests that in the imagery domain environments and objects may be represented separately and may be selectively affected by brain lesions. In the present study, we used functional magnetic resonance imaging (fMRI) to assess the possibility of neural segregation among mental images depicting parts of an object, of an environment (imagined from a first-person perspective), and of a geographical map, using both a mass univariate and a multivariate approach. Data show that different brain areas are involved in different types of mental images. Imagining an environment relies mainly on regions known to be involved in navigational skills, such as the retrosplenial complex and parahippocampal gyrus, whereas imagining a geographical map mainly requires activation of the left angular gyrus, known to be involved in the representation of categorical relations. Imagining a familiar object mainly requires activation of parietal areas involved in visual space analysis in both the imagery and the perceptual domain. We also found that the pattern of activity in most of these areas specifically codes for the spatial arrangement of the parts of the mental image. Our results clearly demonstrate a functional neural segregation for different contents of mental images and suggest that visuospatial information is coded by different patterns of activity in brain areas involved in visual mental imagery. Hum Brain Mapp 36:945-958, 2015.

Structure-activity relationships for α-calcitonin gene-related peptide

Calcitonin gene-related peptide (CGRP) is a member of the calcitonin (CT) family of peptides. It is a widely distributed neuropeptide implicated in conditions such as neurogenic inflammation. With other members of the CT family, it shares an N-terminal disulphide-bonded ring which is essential for biological activity, an area of potential α-helix, and a C-terminal amide. CGRP binds to the calcitonin receptor-like receptor (CLR) in complex with receptor activity-modifying protein 1 (RAMP1), a member of the family B (or secretin-like) GPCRs. It can also activate other CLR or calcitonin-receptor/RAMP complexes. This 37 amino acid peptide comprises the N-terminal ring that is required for receptor activation (residues 1-7); an α-helix (residues 8-18), a region incorporating a β-bend (residues 19-26) and the C-terminal portion (residues 27-37), that is characterized by bends between residues 28-30 and 33-34. A few residues have been identified that seem to make major contributions to receptor binding and activation, with a larger number contributing either to minor interactions (which collectively may be significant), or to maintaining the conformation of the bound peptide. It is not clear if CGRP follows the pattern of other family B GPCRs in binding largely as an α-helix. Linked Articles This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7 © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Pattern recognition analyses of brain activation elicited by happy and neutral faces in unipolar and bipolar depression

Objectives: Recently, pattern recognition approaches have been used to classify patterns of brain activity elicited by sensory or cognitive processes. In the clinical context, these approaches have been mainly applied to classify groups of individuals based on structural magnetic resonance imaging (MRI) data. Only a few studies have applied similar methods to functional MRI (fMRI) data. Methods: We used a novel analytic framework to examine the extent to which unipolar and bipolar depressed individuals differed on discrimination between patterns of neural activity for happy and neutral faces. We used data from 18 currently depressed individuals with bipolar I disorder (BD) and 18 currently depressed individuals with recurrent unipolar depression (UD), matched on depression severity, age, and illness duration, and 18 age- and gender ratio-matched healthy comparison subjects (HC). fMRI data were analyzed using a general linear model and Gaussian process classifiers. Results: The accuracy for discriminating between patterns of neural activity for happy versus neutral faces overall was lower in both patient groups relative to HC. The predictive probabilities for intense and mild happy faces were higher in HC than in BD, and for mild happy faces were higher in HC than UD (all p < 0.001). Interestingly, the predictive probability for intense happy faces was significantly higher in UD than BD (p = 0.03). Conclusions: These results indicate that patterns of whole-brain neural activity to intense happy faces were significantly less distinct from those for neutral faces in BD than in either HC or UD. These findings indicate that pattern recognition approaches can be used to identify abnormal brain activity patterns in patient populations and have promising clinical utility as techniques that can help to discriminate between patients with different psychiatric illnesses.

Imidazolium-based warheads strongly influence activity of water-soluble peptidic transglutaminase inhibitors

New peptidic water-soluble inhibitors are reported. In addition to the carboxylate moiety, a new polar warhead was explored. Depending on the size of its substituents, the newly appended imidazolium scaffold designed to enhance the hydrophilic character of the inhibitors could induce a good inhibition for tissue transglutaminase (TG2) and blood coagulation factor XIIIa (FXIIIa). Correlated with the narrow tunnel that hosts the target catalytic cysteine residue, the various modulations suggest a bent conformation of the ligands as the binding pattern mode. Analogues in the dialkylsulfonium series were also tested and showed specificity for TG2 over FXIIIa. © 2013 Elsevier Masson SAS. All rights reserved.

Cysteine protease gene expression and proteolytic activity during senescence of Alstroemeria petals

The functional life of the flower is terminated by senescence and/or abscission. Multiple processes contribute to produce the visible signs of petal wilting and inrolling that typify senescence, but one of the most important is that of protein degradation and remobilization. This is mediated in many species through protein ubiquitination and the action of specific protease enzymes. This paper reports the changes in protein and protease activity during development and senescence of Alstroemeria flowers, a Liliaceous species that shows very little sensitivity to ethylene during senescence and which shows perianth abscission 8-10 d after flower opening. Partial cDNAs of ubiquitin (ALSUQ1) and a putative cysteine protease (ALSCYP1) were cloned from Alstroemeria using degenerate PCR primers and the expression pattern of these genes was determined semi-quantitatively by RT-PCR. While the levels of ALSUQ1 only fluctuated slightly during floral development and senescence, there was a dramatic increase in the expression of ALSCYP1 indicating that this gene may encode an important enzyme for the proteolytic process in this species. Three papain class cysteine protease enzymes showing different patterns of activity during flower development were identified on zymograms, one of which showed a similar expression pattern to the cysteine protease cDNA.

Evidence of climate variability and tropical cyclone activity from diatom assemblage dynamics in coastal southwest Florida

Estuaries are dynamic on many spatial and temporal scales. Distinguishing effects of unpredictable events from cyclical patterns can be challenging but important to predict the influence of press and pulse drivers in the face of climate change. Diatom assemblages respond rapidly to changing environmental conditions and characterize change on multiple time scales. The goals of this research were to 1) characterize diatom assemblages in the Charlotte Harbor watershed, their relationships with water quality parameters, and how they change in response to climate; and 2) use assemblages in sediment cores to interpret past climate changes and tropical cyclone activity. ^ Diatom assemblages had strong relationships with salinity and nutrient concentrations, and a quantitative tool was developed to reconstruct past values of these parameters. Assemblages were stable between the wet and dry seasons, and were more similar to each other than to assemblages found following a tropical cyclone. Diatom assemblages following the storm showed a decrease in dispersion among sites, a pattern that was consistent on different spatial scales but may depend on hydrological management regimes. ^ Analysis of sediment cores from two southwest Florida estuaries showed that locally-developed diatom inference models can be applied with caution on regional scales. Large-scale climate changes were suggested by environmental reconstructions in both estuaries, but with slightly different temporal pacing. Estimates of salinity and nutrient concentrations suggested that major hydrological patterns changed at approximately 5.5 and 3 kyrs BP. A highly temporally-resolved sediment core from Charlotte Harbor provided evidence for past changes that correspond with known climate records. Diatom assemblages had significant relationships with the three-year average index values of the Atlantic Multidecadal Oscillation and the El Niño Southern Oscillation. Assemblages that predicted low salinity and high total phosphorus also had the lowest dispersion and corresponded with some major storms in the known record, which together may provide a proxy for evidence of severe storms in the paleoecological record. ^

Is socioeconomic position early in life associated with physical activity during adulthood following the accumulation of risk model with additive effects?

L'activité physique améliore la santé, mais seulement 4.8% des Canadiens atteignent le niveau recommandé. La position socio-économique est un des déterminants de l'activité physique les plus importants. Elle est associée à l’activité physique de manière transversale à l’adolescence et à l’âge adulte. Cette thèse a tenté de déterminer s'il y a une association à long terme entre la position socio-économique au début du parcours de vie et l’activité physique à l’âge adulte. S'il y en avait une, un deuxième objectif était de déterminer quel modèle théorique en épidémiologie des parcours de vie décrivait le mieux sa forme. Cette thèse comprend trois articles: une recension systématique et deux recherches originales. Dans la recension systématique, des recherches ont été faites dans Medline et EMBASE pour trouver les études ayant mesuré la position socio-économique avant l'âge de 18 ans et l'activité physique à ≥18 ans. Dans les deux recherches originales, la modélisation par équations structurelles a été utilisée pour comparer trois modèles alternatifs en épidémiologie des parcours de vie: le modèle d’accumulation de risque avec effets additifs, le modèle d’accumulation de risque avec effet déclenché et le modèle de période critique. Ces modèles ont été comparés dans deux cohortes prospectives représentatives à l'échelle nationale: la 1970 British birth cohort (n=16,571; première recherche) et l’Enquête longitudinale nationale sur les enfants et les jeunes (n=16,903; deuxième recherche). Dans la recension systématique, 10 619 articles ont été passés en revue par deux chercheurs indépendants et 42 ont été retenus. Pour le résultat «activité physique» (tous types et mesures confondus), une association significative avec la position socio-économique durant l’enfance fut trouvée dans 26/42 études (61,9%). Quand seulement l’activité physique durant les loisirs a été considérée, une association significative fut trouvée dans 21/31 études (67,7%). Dans un sous-échantillon de 21 études ayant une méthodologie plus forte, les proportions d’études ayant trouvé une association furent plus hautes : 15/21 (71,4%) pour tous les types et toutes les mesures d’activité physique et 12/15 (80%) pour l’activité physique de loisir seulement. Dans notre première recherche originale sur les données de la British birth cohort, pour la classe sociale, nous avons trouvé que le modèle d’accumulation de risque avec effets additifs s’est ajusté le mieux chez les hommes et les femmes pour l’activité physique de loisir, au travail et durant les transports. Dans notre deuxième recherche originale sur les données canadiennes sur l'activité physique de loisir, nous avons trouvé que chez les hommes, le modèle de période critique s’est ajusté le mieux aux données pour le niveau d’éducation et le revenu, alors que chez les femmes, le modèle d’accumulation de risque avec effets additifs s’est ajusté le mieux pour le revenu, tandis que le niveau d’éducation ne s’est ajusté à aucun des modèles testés. En conclusion, notre recension systématique indique que la position socio-économique au début du parcours de vie est associée à la pratique d'activité physique à l'âge adulte. Les résultats de nos deux recherches originales suggèrent un patron d’associations le mieux représenté par le modèle d’accumulation de risque avec effets additifs.

Benthos activity, abundance and biomass in surface sediments off Morocco, Northwest Africa

Macro- and meiobenthic abundance and biomass as well as metabolic activity (respiration, ETS activity) have been studied along a transect ranging from 130 to 3000 m water depth off northern Morocco (35° N) during "Meteor" cruise No. 53 (1980). The distribution of chloroplastic pigment concentration (chlorophyll a, pheophytins) in the sediment has been investigated as a measure of sedimented primary organic matter. High chloroplastic pigment concentrations were found on the shelf and around the shelf break, but values declined rapidly between 200 and 600 m depth. Below 1200 m pigment concentrations remained at a relatively uniform low level. Macrobenthic abundance and biomass (wet weight) decreased with increasing water depth and with distance from the shore. Significant changes occurred between the shelf and upper slope and below 2000 m depth. Meiobenthic abundance and biomass (ash free dry weight) followed the same general pattern, but changes were found below 400 and 800 m depth. In the depth range of 1200 to 3000 m values differ only slightly. Meiofauna abundance and biomass show a good correlation with the sedimentary chloroplastic pigment concentrations. Respiratory activity of sediment cores, measured by a shipboard technique at ambient temperatures, decreased with water depth and shows a good correlation with the pigment concentrations. ETS activity was highest on the shelf and decreased with water depth, with significant changes between 200 and 400 m, and below 1200 m depth, respectively. Activity was generally highest in the top 5 cm of the sediment and was measurable, at all stations, down to 15 cm sediment depth. Shelf and upper slope stations exhibited a vertical distribution pattern of ETS activity in the sediment column, different from that of deeper stations. The importance of biological activity measurements as an estimate of productivity is discussed. To prove the thesis that differences in benthic abundance, biomass and activity reflect differences in pelagic surface primary production, in the case of the NW-African coast caused by different upwelling intensities, the values from 35° N were compared with data from 21° N (permanent upwelling activity) and 17° N (ca. 9 months upwelling per year). On the shelf and upper slope (< 500 m) hydrographical conditions (currents, internal waves) influence the deposition of organic matter and cause a biomass minimum between 200 and 400 m depth in some regions. But, in general, macrobenthic abundance and biomass increases with enhanced upwelling activity and reaches a maximum in the area off Cape Blanc (21° N). On the shelf and in the shelf break region meiofauna densities are higher at 35° N in comparison to 21° N; but in contrast to the decreasing meiofauna abundance with increasing water depth at 35° N, an abundance maximum between 400 and 1200 m depth is formed in the Cape Blanc region; this maximum coincides with the maximum of sedimentary chloroplastic pigment equivalents. The comparison of ETS activities between 35° N and 21° N shows on the shelf activity at 21° N is up to 14 times higher and on the slope 4-9 times higher, which demonstrates that benthic activity responds to the surface productivity regime.

Exploring the role of the α-carboxyphosphonate moiety in the HIV-RT activity of α-carboxy nucleoside phosphonates

As α-carboxy nucleoside phosphonates (α-CNPs) have demonstrated a novel mode of action of HIV-1 reverse transcriptase inhibition, structurally related derivatives were synthesized, namely the malonate 2, the unsaturated and saturated bisphosphonates 3 and 4, respectively and the amide 5. These compounds were evaluated for inhibition of HIV-1 reverse transcriptase in cell-free assays. The importance of the α-carboxy phosphonoacetic acid moiety for achieving reverse transcriptase inhibition, without the need for prior phosphorylation, was confirmed. The malonate derivative 2 was less active by two orders of magnitude than the original α-CNPs, while displaying the same pattern of kinetic behavior; interestingly the activity resides in the “L”-enantiomer of 2, as seen with the earlier series of α-CNPs. A crystal structure with an RT/DNA complex at 2.95 Å resolution revealed the binding of the “L”-enantiomer of 2, at the polymerase active site with a weaker metal ion chelation environment compared to 1a (T-α-CNP) which may explain the lower inhibitory activity of 2.

Inhibitory Effects Of A Cured Antibacterial Bonding System On Viability And Metabolic Activity Of Oral Bacteria.

To evaluate the antimicrobial efficacy of Clearfil SE Protect (CP) and Clearfil SE Bond (CB) after curing and rinsed against five individual oral microorganisms as well as a mixture of bacterial culture prepared from the selected test organisms. Bacterial suspensions were prepared from single species of Streptococcus mutans, Streptococcus sobrinus, Streptococcus gordonii, Actinomyces viscosus and Lactobacillus lactis, as well as mixed bacterial suspensions from these organisms. Dentin bonding system discs (6 mm×2 mm) were prepared, cured, washed and placed on the bacterial suspension of single species or multispecies bacteria for 15, 30 and 60 min. MTT, Live/Dead bacterial viability (antibacterial effect), and XTT (metabolic activity) assays were used to test the two dentin system's antibacterial effect. All assays were done in triplicates and each experiment repeated at least three times. Data were submitted to ANOVA and Scheffe's f-test (5%). Greater than 40% bacteria killing was seen within 15 min, and the killing progressed with increasing time of incubation with CP discs. However, a longer (60 min) period of incubation was required by CP to achieve similar antimicrobial effect against mixed bacterial suspension. CB had no significant effect on the viability or metabolic activity of the test microorganisms when compared to the control bacterial culture. CP was significantly effective in reducing the viability and metabolic activity of the test organisms. The results demonstrated the antimicrobial efficacy of CP both on single and multispecies bacterial culture. CP may be beneficial in reducing bacterial infections in cavity preparations in clinical dentistry.

Vascular Pattern In Enchondroma And Chondrosarcoma: Clinical And Immunohistologic Study.

Although cartilaginous tumors have low microvascular density, vessels are important for the provision of nutrition so that the tumor can grow and generate metastasis. The aim of this study was to assess the value of the vascular pattern classification as a prognostic tool in chondrosarcomas (CSs) and its relation with vascular endothelial growth factor (VEGF) expression. This was a retrospective study of 21 enchondromas and 57 conventional CSs. Clinical data and outcome were retrieved from medical files. CSs histologic grades (on a scale of 1 to 3) were determined according to the World Health Organization classification. The vascular pattern (on a scale of A to C) was assessed through CD34, according to Kalinski. CD105 and VEGF were also evaluated. Poor outcome was significantly associated with vascular pattern groups B and C. Higher vascular pattern were 6.5 times more frequent in moderate-grade and high-grade CSs than in grade 1 CS. On multivariate analysis, a clear correlation was found between VEGF overexpression and B/C vascular patterns. Only 18 (benign and malignant) tumors stained for CD105. The results point to the use of the vascular pattern classification as a prognostic tool in CSs and to differentiate low-grade from moderate-grade/high-grade CSs. Vascular pattern might be also used to complement histologic grade, VEGF immunostaining, and microvascular density, for indicating a patient's prognosis. Low-grade CSs develop under low neoangiogenesis, which conforms to the slow growth rate of these tumors.

Design, Synthesis And Biological Evaluation Of Hybrid Bioisoster Derivatives Of N-acylhydrazone And Furoxan Groups With Potential And Selective Anti-trypanosoma Cruzi Activity.

Hybrid bioisoster derivatives from N-acylhydrazones and furoxan groups were designed with the objective of obtaining at least a dual mechanism of action: cruzain inhibition and nitric oxide (NO) releasing activity. Fifteen designed compounds were synthesized varying the substitution in N-acylhydrazone and in furoxan group as well. They had its anti-Trypanosoma cruzi activity in amastigotes forms, NO releasing potential and inhibitory cruzain activity evaluated. The two most active compounds (6, 14) both in the parasite amastigotes and in the enzyme contain the nitro group in para position of the aromatic ring. The permeability screening in Caco-2 cell and cytotoxicity assay in human cells were performed for those most active compounds and both showed to be less cytotoxic than the reference drug, benznidazole. Compound 6 was the most promising, since besides activity it showed good permeability and selectivity index, higher than the reference drug. Thereby the compound 6 was considered as a possible candidate for additional studies.

Primary Relapse Site Pattern In Women With Triple-negative Breast Cancer.

Despite the remarkable improvements in breast cancer (BC) characterization, accurate prediction of BC clinical behavior is often still difficult to achieve. Some studies have investigated the association between the molecular subtype, namely the basal-like BC and the pattern of relapse, however only few investigated the association between relapse pattern and immunohistochemical defined triple-negative breast cancers (TNBCs). The aim of this study was to evaluate the pattern of relapse in patients with TNBC, namely the primary distant relapse site. One-hundred twenty nine (129) invasive breast carcinomas with follow-up information were classified according to the molecular subtype using immunohistochemistry for ER, PgR and Her2. The association between TNBC and distant relapse primary site was analyzed by logistic regression. Using multivariate logistic regression analysis patients with TNBC displayed only 0.09 (95% CI: 0.00-0.74; p=0.02) the odds of the non-TNBC patients of developing bone primary relapse. Regarding visceral and lymph-node relapse, no differences between in this cohort were found. Though classically regarded as aggressive tumors, TNBCs rarely development primary relapse in bone when compared to non-TNBC, a clinical relevant fact when investigating a metastasis of an occult or non-sampled primary BC.