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1.
Caroline Blais Daniel Fiset Martin Arguin Pierre Jolicoeur Daniel Bub Frédéric Gosselin 《PloS one》2009,4(7)
Background
Skilled adult readers, in contrast to beginners, show no or little increase in reading latencies as a function of the number of letters in words up to seven letters. The information extraction strategy underlying such efficiency in word identification is still largely unknown, and methods that allow tracking of the letter information extraction through time between eye saccades are needed to fully address this question.Methodology/Principal Findings
The present study examined the use of letter information during reading, by means of the Bubbles technique. Ten participants each read 5,000 five-letter French words sampled in space-time within a 200 ms window. On the temporal dimension, our results show that two moments are especially important during the information extraction process. On the spatial dimension, we found a bias for the upper half of words. We also show for the first time that letter positions four, one, and three are particularly important for the identification of five-letter words.Conclusions/Significance
Our findings are consistent with either a partially parallel reading strategy or an optimal serial reading strategy. We show using computer simulations that this serial reading strategy predicts an absence of a word-length effect for words from four- to seven letters in length. We believe that the Bubbles technique will play an important role in further examining the nature of reading between eye saccades. 相似文献2.
Background
Can hearing a word change what one sees? Although visual sensitivity is known to be enhanced by attending to the location of the target, perceptual enhancements of following cues to the identity of an object have been difficult to find. Here, we show that perceptual sensitivity is enhanced by verbal, but not visual cues.Methodology/Principal Findings
Participants completed an object detection task in which they made an object-presence or -absence decision to briefly-presented letters. Hearing the letter name prior to the detection task increased perceptual sensitivity (d′). A visual cue in the form of a preview of the to-be-detected letter did not. Follow-up experiments found that the auditory cuing effect was specific to validly cued stimuli. The magnitude of the cuing effect positively correlated with an individual measure of vividness of mental imagery; introducing uncertainty into the position of the stimulus did not reduce the magnitude of the cuing effect, but eliminated the correlation with mental imagery.Conclusions/Significance
Hearing a word made otherwise invisible objects visible. Interestingly, seeing a preview of the target stimulus did not similarly enhance detection of the target. These results are compatible with an account in which auditory verbal labels modulate lower-level visual processing. The findings show that a verbal cue in the form of hearing a word can influence even the most elementary visual processing and inform our understanding of how language affects perception. 相似文献3.
Background
Several recent studies have revealed that words presented with a small increase in interletter spacing are identified faster than words presented with the default interletter spacing (i.e., w a t e r faster than water). Modeling work has shown that this advantage occurs at an early encoding level. Given the implications of this finding for the ease of reading in the new digital era, here we examined whether the beneficial effect of small increases in interletter spacing can be generalized to a normal reading situation.Methodology
We conducted an experiment in which the participant’s eyes were monitored when reading sentences varying in interletter spacing: i) sentences were presented with the default (0.0) interletter spacing; ii) sentences presented with a +1.0 interletter spacing; and iii) sentences presented with a +1.5 interletter spacing.Principal Findings
Results showed shorter fixation duration times as an inverse function of interletter spacing (i.e., fixation durations were briefest with +1.5 spacing and slowest with the default spacing).Conclusions
Subtle increases in interletter spacing facilitate the encoding of the fixated word during normal reading. Thus, interletter spacing is a parameter that may affect the ease of reading, and it could be adjustable in future implementations of e-book readers. 相似文献4.
Background
Normal reading requires eye guidance and activation of lexical representations so that words in text can be identified accurately. However, little is known about how the visual content of text supports eye guidance and lexical activation, and thereby enables normal reading to take place.Methods and Findings
To investigate this issue, we investigated eye movement performance when reading sentences displayed as normal and when the spatial frequency content of text was filtered to contain just one of 5 types of visual content: very coarse, coarse, medium, fine, and very fine. The effect of each type of visual content specifically on lexical activation was assessed using a target word of either high or low lexical frequency embedded in each sentenceResults
No type of visual content produced normal eye movement performance but eye movement performance was closest to normal for medium and fine visual content. However, effects of lexical frequency emerged early in the eye movement record for coarse, medium, fine, and very fine visual content, and were observed in total reading times for target words for all types of visual content.Conclusion
These findings suggest that while the orchestration of multiple scales of visual content is required for normal eye-guidance during reading, a broad range of visual content can activate processes of word identification independently. Implications for understanding the role of visual content in reading are discussed. 相似文献5.
Background
Giant cell arteritis (GCA) and Takayasu''s arteritis (TAA) are large vessel vasculitides (LVV) for which corticosteroids (CS) are the mainstay for treatment. In patients with LVV unable to tolerate CS, biological agents have been used with variable effectiveness.Objective
To systematically review the effectiveness and safety of biological agents in patients with LVV.Methods
We searched 5 electronic databases (inception to October 2012) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. Our protocol was registered in PROSPERO.Results
We included 25 studies (3 RCTs and 22 case series with ≥2 cases). 95 GCA and 98 TAA patients received biological agents. The RCTs using anti-TNF agents (infliximab, etanercept and adalimumab) did not suggest a benefit in GCA. GCA patients receiving tocilizumab, in case series, achieved remission (19 patients) and reduction of corticosteroid dose (mean difference, –16.55 mg/day (95% CI: –26.24, –6.86)). In case series, 75 patients with refractory TAA treated with infliximab discontinued CS 32% of the time. Remission was variably defined and the studies were clinically heterogeneous which precluded further analysis.Conclusion
This systematic review demonstrated a weak evidence base on which to assess the effectiveness of biological treatment in LVV. Evidence from RCTs suggests that anti-TNF agents are not effective for remission or reduction of CS use. Tocilizumab and infliximab may be effective in the management of LVV and refractory TAA, respectively, although the evidence comes from case series. Future analytical studies are needed to confirm these findings. 相似文献6.
Background
In acupuncture brain imaging trials, there are many non-acupuncture factors confounding the neuronal mapping. The modality of the placebo, subjects’ psychological attitude to acupuncture and their physical state are the three most confounding factors.Objective
To obtain more precise and accurate cerebral fMRI mapping of acupuncture.Design and Setting
A 2×2 randomized, controlled, participant-blinded cross-over factorial acupuncture trial was conducted at Xuanwu Hospital in Beijing, China.Participants
Forty-one college students with myopia were recruited to participate in our study and were allocated randomly to four groups, Group A, Group B, Group C and Group D.Interventions
Group A received real acupuncture (RA) and treatment instruction (TI); Group B received RA and non-treatment instruction (NI); Group C received sham acupuncture (SA) and TI; Group D received SA and NI.Results
Stimulation at LR3 activated some areas of the visual cortex, and the cerebral response to non-acupuncture factors was complex and occurred in multiple areas.Conclusions
The results provide more evidence regarding the credibility of acupuncture therapy and suggest that more precise experimental designs are needed to eliminate sources of bias in acupuncture controlled trials and to obtain sound results. 相似文献7.
Merabet LB Hamilton R Schlaug G Swisher JD Kiriakopoulos ET Pitskel NB Kauffman T Pascual-Leone A 《PloS one》2008,3(8):e3046
Background
The loss of vision has been associated with enhanced performance in non-visual tasks such as tactile discrimination and sound localization. Current evidence suggests that these functional gains are linked to the recruitment of the occipital visual cortex for non-visual processing, but the neurophysiological mechanisms underlying these crossmodal changes remain uncertain. One possible explanation is that visual deprivation is associated with an unmasking of non-visual input into visual cortex.Methodology/Principal Findings
We investigated the effect of sudden, complete and prolonged visual deprivation (five days) in normally sighted adult individuals while they were immersed in an intensive tactile training program. Following the five-day period, blindfolded subjects performed better on a Braille character discrimination task. In the blindfold group, serial fMRI scans revealed an increase in BOLD signal within the occipital cortex in response to tactile stimulation after five days of complete visual deprivation. This increase in signal was no longer present 24 hours after blindfold removal. Finally, reversible disruption of occipital cortex function on the fifth day (by repetitive transcranial magnetic stimulation; rTMS) impaired Braille character recognition ability in the blindfold group but not in non-blindfolded controls. This disruptive effect was no longer evident once the blindfold had been removed for 24 hours.Conclusions/Significance
Overall, our findings suggest that sudden and complete visual deprivation in normally sighted individuals can lead to profound, but rapidly reversible, neuroplastic changes by which the occipital cortex becomes engaged in processing of non-visual information. The speed and dynamic nature of the observed changes suggests that normally inhibited or masked functions in the sighted are revealed by visual loss. The unmasking of pre-existing connections and shifts in connectivity represent rapid, early plastic changes, which presumably can lead, if sustained and reinforced, to slower developing, but more permanent structural changes, such as the establishment of new neural connections in the blind. 相似文献8.
Background
Macromolecule mobility is often quantified with Fluorescence Recovery After Photobleaching (FRAP). Throughout literature a wide range of diffusion coefficients for GFP in the cytoplasm of Escherichia coli (3 to 14 µm2/s) is reported using FRAP-based approaches. In this study, we have evaluated two of these methods: pulsed-FRAP and “conventional”-FRAP.Principal Findings
To address the question whether the apparent discrepancy in the diffusion data stems from methodological differences or biological variation, we have implemented and compared the two techniques on bacteria grown and handled in the same way. The GFP diffusion coefficients obtained under normal osmotic conditions and upon osmotic upshift were very similar for the different techniques.Conclusions
Our analyses indicate that the wide range of values reported for the diffusion coefficient of GFP in live cells are due to experimental conditions and/or biological variation rather than methodological differences. 相似文献9.
Objective
To investigate the effects of social isolation on oral mucosal healing in rats, and to determine if wound-associated genes and microRNAs (miRNAs) may contribute to this response.Methods
Rats were group housed or socially isolated for 4 weeks before a 3.5 mm wound was placed on the hard oral palate. Wound closure was assessed daily and tissues were collected for determination of gene expression levels and miRNAs (i.e., miR-29a,b,c and miR-203). The predicted target of these microRNAs (i.e., vascular endothelial growth factor A, VEGFA) was functionally validated.Results
Social isolation stress delayed the healing process of oral palatal mucosal wounds in rats. Lower mRNA levels of interleukin-1β (IL1β), macrophage inflammatory p r o t e i n-1α (MIP1α), fibroblast growth factor 7 (FGF7), and VEGFA were found in the biopsied tissues of isolated animals on days 1 and/or 3 post-wounding. Intriguingly, the isolated rats persistently exhibited higher levels of miR-29 family members and miR-203. Our results confirmed that VEGFA is a direct target of these miRNAs, as both miR-29a,c and miR-203 strongly and specifically suppressed endogenous VEGFA expression in vitro.Conclusions
This study in rats demonstrates for the first time that social isolation delays oral mucosal healing, and suggests a potential role for healing-associated gene and miRNA interactions during this process via modulation of VEGF expression. 相似文献10.
Guerra L Carr HS Richter-Dahlfors A Masucci MG Thelestam M Frost JA Frisan T 《PloS one》2008,3(5):e2254
Background
Exposure of adherent cells to DNA damaging agents, such as the bacterial cytolethal distending toxin (CDT) or ionizing radiations (IR), activates the small GTPase RhoA, which promotes the formation of actin stress fibers and delays cell death. The signalling intermediates that regulate RhoA activation and promote cell survival are unknown.Principal Findings
We demonstrate that the nuclear RhoA-specific Guanine nucleotide Exchange Factor (GEF) Net1 becomes dephosphorylated at a critical inhibitory site in cells exposed to CDT or IR. Expression of a dominant negative Net1 or Net1 knock down by iRNA prevented RhoA activation, inhibited the formation of stress fibers, and enhanced cell death, indicating that Net1 activation is required for this RhoA-mediated responses to genotoxic stress. The Net1 and RhoA-dependent signals involved activation of the Mitogen-Activated Protein Kinase p38 and its downstream target MAPK-activated protein kinase 2.Significance
Our data highlight the importance of Net1 in controlling RhoA and p38 MAPK mediated cell survival in cells exposed to DNA damaging agents and illustrate a molecular pathway whereby chronic exposure to a bacterial toxin may promote genomic instability. 相似文献11.
Background
Previous literature suggests that those with reading disability (RD) have more pronounced deficits during semantic processing in reading as compared to listening comprehension. This discrepancy has been supported by recent neuroimaging studies showing abnormal activity in RD during semantic processing in the visual but not in the auditory modality. Whether effective connectivity between brain regions in RD could also show this pattern of discrepancy has not been investigated.Methodology/Principal Findings
Children (8- to 14-year-olds) were given a semantic task in the visual and auditory modality that required an association judgment as to whether two sequentially presented words were associated. Effective connectivity was investigated using Dynamic Causal Modeling (DCM) on functional magnetic resonance imaging (fMRI) data. Bayesian Model Selection (BMS) was used separately for each modality to find a winning family of DCM models separately for typically developing (TD) and RD children. BMS yielded the same winning family with modulatory effects on bottom-up connections from the input regions to middle temporal gyrus (MTG) and inferior frontal gyrus(IFG) with inconclusive evidence regarding top-down modulations. Bayesian Model Averaging (BMA) was thus conducted across models in this winning family and compared across groups. The bottom-up effect from the fusiform gyrus (FG) to MTG rather than the top-down effect from IFG to MTG was stronger in TD compared to RD for the visual modality. The stronger bottom-up influence in TD was only evident for related word pairs but not for unrelated pairs. No group differences were noted in the auditory modality.Conclusions/Significance
This study revealed a modality-specific deficit for children with RD in bottom-up effective connectivity from orthographic to semantic processing regions. There were no group differences in connectivity from frontal regions, suggesting that the core deficit in RD is not in top-down modulation. 相似文献12.
13.
Single Tube,High Throughput Cloning of Inverted Repeat Constructs for Double-Stranded RNA Expression
Background
RNA interference (RNAi) has emerged as a powerful tool for the targeted knockout of genes for functional genomics, system biology studies and drug discovery applications. To meet the requirements for high throughput screening in plants we have developed a new method for the rapid assembly of inverted repeat-containing constructs for the in vivo production of dsRNAs.Methodology/Principal Findings
The procedure that we describe is based on tagging the sense and antisense fragments with unique single-stranded (ss) tails which are then assembled in a single tube Ligase Independent Cloning (LIC) reaction. Since the assembly reaction is based on the annealing of unique complementary single stranded tails which can only assemble in one orientation, greater than ninety percent of the resultant clones contain the desired insert.Conclusion/Significance
Our single-tube reaction provides a highly efficient method for the assembly of inverted repeat constructs for gene suppression applications. The single tube assembly is directional, highly efficient and readily adapted for high throughput applications. 相似文献14.
Katsuo Fujiwara Kenji Kunita Naoe Kiyota Aida Mammadova Mariko Irei 《Journal of physiological anthropology》2012,31(1):31
Background
A flexed neck posture leads to non-specific activation of the brain. Sensory evoked cerebral potentials and focal brain blood flow have been used to evaluate the activation of the sensory cortex. We investigated the effects of a flexed neck posture on the cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in the related sensory cortices.Methods
Twelve healthy young adults received right visual hemi-field, binaural auditory and left median nerve stimuli while sitting with the neck in a resting and flexed (20° flexion) position. Sensory evoked potentials were recorded from the right occipital region, Cz in accordance with the international 10–20 system, and 2 cm posterior from C4, during visual, auditory and somatosensory stimulations. The oxidative-hemoglobin concentration was measured in the respective sensory cortex using near-infrared spectroscopy.Results
Latencies of the late component of all sensory evoked potentials significantly shortened, and the amplitude of auditory evoked potentials increased when the neck was in a flexed position. Oxidative-hemoglobin concentrations in the left and right visual cortices were higher during visual stimulation in the flexed neck position. The left visual cortex is responsible for receiving the visual information. In addition, oxidative-hemoglobin concentrations in the bilateral auditory cortex during auditory stimulation, and in the right somatosensory cortex during somatosensory stimulation, were higher in the flexed neck position.Conclusions
Visual, auditory and somatosensory pathways were activated by neck flexion. The sensory cortices were selectively activated, reflecting the modalities in sensory projection to the cerebral cortex and inter-hemispheric connections. 相似文献15.
Objective
To evaluate the presence of clinical signs consistent with suspected glaucoma in Haitian Afro-Caribbean individuals residing in South Florida who do not receive regular eye examinations.Design
Retrospective, cross-sectional study.Methods
SETTING: Community health center in the Little Haiti district of Miami, Florida. PATIENT POPULATION: We reviewed medical records and screening forms from five health screenings between October 2011 to October 2013 of 939 Afro-Caribbean individuals older than 18 years, who were never diagnosed with glaucoma or had an eye examination within the last ten years. PROCEDURES: Measurements of distance visual acuity (VA), intraocular eye pressure (IOP), central corneal thickness (CCT), cup-to-disc ratio (CDR), frequency doubling technology (FDT) perimeter visual field (VF).Main Outcome Measures
Proportion of glaucoma suspects, based on IOP greater than or equal to 24 mm Hg or CDR greater than or equal to 0.7 in either eye, and determinants of CDR and IOP.Results
One hundred ninety-one (25.5%) of 750 patients were identified as glaucoma suspects. Glaucoma suspects were common in both the youngest and oldest age groups (<40 years, 20.9%; 95% confidence interval [CI], 17.9–23.9; >70 years, 25.0%; 95% CI, 21.8–28.2) and higher in men than women less than 70 years; the reverse was true after 70 years. Among all patients, mean IOP was 19.2±4.5 mmHg, mean CDR was 0.37±0.17, and mean CCT was 532±37.1 µm. In multiple linear stepwise regression analysis, determinates of increased CDR included increasing age (P = 0.004), lack of insurance (P = 0.019), and higher IOP (P<0.001), while increasing CDR (P<0.001) and thicker CCT (P<0.001) were associated with higher IOP.Conclusions
This first glaucoma survey in a U.S. Haitian Afro-Caribbean population indicates glaucoma suspect status is high across all age groups, and suggests glaucoma monitoring in people less than 40 years of age is indicated in this population. 相似文献16.
Hilda T. Draeger Shervin Assassi Roozbeh Sharif Emilio B. Gonzalez Brock E. Harper Frank C. Arnett Ameena Manzoor Richard A. Lange Maureen D. Mayes 《PloS one》2013,8(10)
Objective
To evaluate the prognostic significance of baseline electrocardiogram (ECG) abnormalities in a multiethnic cohort of patients with early systemic sclerosis (SSc) and to determine the serological, clinical, and echocardiogram correlates of ECG findings.Methods
SSc patients with disease duration of≤5 years were enrolled in the GENISOS (Genetics versus Environment in Scleroderma Outcome Study) cohort. At the first visit, a standard 12 lead ECG was obtained along with demographic information, clinical data, and autoantibodies. The results of echocardiograms were also recorded. All ECGs were interpreted by a cardiologist unaware of the patients'' clinical data.Results
Of 265 SSc patients with average disease duration at enrollment of 2.5 years, 140 (52.8%) had abnormal ECG findings. These findings were not associated with SSc disease type or autoantibody profile but were associated with more severe heart and lung involvement. A total of 75 patients (28.3%) died over a follow up time of 9.9 years. Complete right bundle branch block (± left anterior hemiblock) on ECG, present in 7 (2.6%) patients, predicted a higher risk of mortality (HR: 5.3; 95% CI: 2.1 to 13.4; p<0.001). The predictive significance of right bundle branch block was independent of age at enrollment, gender, ethnicity and risk factors for coronary artery disease.Conclusion
ECG abnormalities are common in patients with early SSc and are associated with the severity of lung and heart involvement. Right bundle branch block is an independent predictor of mortality, and should be considered a marker of disease severity in SSc. 相似文献17.
Purpose
To evaluate how the monitoring and treatment for diabetic macular edema (DME) has changed in a national sample.Design
Retrospective cohort study.Methods
Setting: Administrative medical claims data from a large, national U.S. insurer. Study population: Beneficiaries of a U.S. insurance company. Observation procedures: All incident cases of DME were found. Those in years 2002/3, 2006 and 2010 were followed for a 2-year observation period and those from 2009, 2010 and 2011 for a 1-year observation period. Main Outcome Measures: Types and frequencies of treatment were tallied and compared over each of the cohorts.Results
Two-year cohorts had 233, 251 and 756 patients in 2002/3, 2006 and 2010 respectively. One-year cohorts had 1002, 1119 and 1382 patients in 2009, 2010 and 2011, respectively. Both percentage of patients receiving therapy and number of treatments given increased across the 2-year cohorts for both focal laser and anti-vascular endothelial growth factor (anti-VEGF) (p<0.001). The highest use of anti-VEGF agents in any of the cohorts was in the 2011 1-year group that only averaged 3.78 injections. Focal laser was used 2.5x as frequently as anti-VEGF injections in the most recent cohorts with only a high of 14.0% of DME patients receiving anti-VEGF therapy in any of the cohorts.Conclusion
Regardless of treatment modality (laser or injection) DME patients received vastly fewer treatments than patients in randomized control trials. Despite the proven superior visual outcomes of anti-VEGF agents over focal laser in DME, focal laser was still used more frequently. 相似文献18.
Background
The carboxysome is a bacterial microcompartment that consists of a polyhedral protein shell filled with ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO), the enzyme that catalyzes the first step of CO2 fixation via the Calvin-Benson-Bassham cycle.Methodology/Principal Findings
To analyze the role of RubisCO in carboxysome biogenesis in vivo we have created a series of Halothiobacillus neapolitanus RubisCO mutants. We identified the large subunit of the enzyme as an important determinant for its sequestration into α-carboxysomes and found that the carboxysomes of H. neapolitanus readily incorporate chimeric and heterologous RubisCO species. Intriguingly, a mutant lacking carboxysomal RubisCO assembles empty carboxysome shells of apparently normal shape and composition.Conclusions/Significance
These results indicate that carboxysome shell architecture is not determined by the enzyme they normally sequester. Our study provides, for the first time, clear evidence that carboxysome contents can be manipulated and suggests future nanotechnological applications that are based upon engineered protein microcompartments. 相似文献19.
Fabio Richlan Denise Sturm Matthias Schurz Martin Kronbichler Gunther Ladurner Heinz Wimmer 《PloS one》2010,5(8)
Background
We used fMRI to examine functional brain abnormalities of German-speaking dyslexics who suffer from slow effortful reading but not from a reading accuracy problem. Similar to acquired cases of letter-by-letter reading, the developmental cases exhibited an abnormal strong effect of length (i.e., number of letters) on response time for words and pseudowords.Results
Corresponding to lesions of left occipito-temporal (OT) regions in acquired cases, we found a dysfunction of this region in our developmental cases who failed to exhibit responsiveness of left OT regions to the length of words and pseudowords. This abnormality in the left OT cortex was accompanied by absent responsiveness to increased sublexical reading demands in phonological inferior frontal gyrus (IFG) regions. Interestingly, there was no abnormality in the left superior temporal cortex which—corresponding to the onological deficit explanation—is considered to be the prime locus of the reading difficulties of developmental dyslexia cases.Conclusions
The present functional imaging results suggest that developmental dyslexia similar to acquired letter-by-letter reading is due to a primary dysfunction of left OT regions. 相似文献20.