3DScapeCS: application of three dimensional, parallel, dynamic network visualization in Cytoscape

PubMed Central

2013-01-01

Background The exponential growth of gigantic biological data from various sources, such as protein-protein interaction (PPI), genome sequences scaffolding, Mass spectrometry (MS) molecular networking and metabolic flux, demands an efficient way for better visualization and interpretation beyond the conventional, two-dimensional visualization tools. Results We developed a 3D Cytoscape Client/Server (3DScapeCS) plugin, which adopted Cytoscape in interpreting different types of data, and UbiGraph for three-dimensional visualization. The extra dimension is useful in accommodating, visualizing, and distinguishing large-scale networks with multiple crossed connections in five case studies. Conclusions Evaluation on several experimental data using 3DScapeCS and its special features, including multilevel graph layout, time-course data animation, and parallel visualization has proven its usefulness in visualizing complex data and help to make insightful conclusions. PMID:24225050

Encoding of Discriminative Fear Memory by Input-Specific LTP in the Amygdala.

PubMed

Kim, Woong Bin; Cho, Jun-Hyeong

2017-08-30

In auditory fear conditioning, experimental subjects learn to associate an auditory conditioned stimulus (CS) with an aversive unconditioned stimulus. With sufficient training, animals fear conditioned to an auditory CS show fear response to the CS, but not to irrelevant auditory stimuli. Although long-term potentiation (LTP) in the lateral amygdala (LA) plays an essential role in auditory fear conditioning, it is unknown whether LTP is induced selectively in the neural pathways conveying specific CS information to the LA in discriminative fear learning. Here, we show that postsynaptically expressed LTP is induced selectively in the CS-specific auditory pathways to the LA in a mouse model of auditory discriminative fear conditioning. Moreover, optogenetically induced depotentiation of the CS-specific auditory pathways to the LA suppressed conditioned fear responses to the CS. Our results suggest that input-specific LTP in the LA contributes to fear memory specificity, enabling adaptive fear responses only to the relevant sensory cue. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

Parallel cascade selection molecular dynamics (PaCS-MD) to generate conformational transition pathway

NASA Astrophysics Data System (ADS)

Harada, Ryuhei; Kitao, Akio

2013-07-01

Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.

Effects of Milk vs Dark Chocolate Consumption on Visual Acuity and Contrast Sensitivity Within 2 Hours: A Randomized Clinical Trial.

PubMed

Rabin, Jeff C; Karunathilake, Nirmani; Patrizi, Korey

2018-04-26

Consumption of dark chocolate can improve blood flow, mood, and cognition in the short term, but little is known about the possible effects of dark chocolate on visual performance. To compare the short-term effects of consumption of dark chocolate with those of milk chocolate on visual acuity and large- and small-letter contrast sensitivity. A randomized, single-masked crossover design was used to assess short-term visual performance after consumption of a dark or a milk chocolate bar. Thirty participants without pathologic eye disease each consumed dark and milk chocolate in separate sessions, and within-participant paired comparisons were used to assess outcomes. Testing was conducted at the Rosenberg School of Optometry from June 25 to August 15, 2017. Visual acuity (in logMAR units) and large- and small-letter contrast sensitivity (in the log of the inverse of the minimum detectable contrast [logCS units]) were measured 1.75 hours after consumption of dark and milk chocolate bars. Among the 30 participants (9 men and 21 women; mean [SD] age, 26 [5] years), small-letter contrast sensitivity was significantly higher after consumption of dark chocolate (mean [SE], 1.45 [0.04] logCS) vs milk chocolate (mean [SE], 1.30 [0.05] logCS; mean improvement, 0.15 logCS [95% CI, 0.08-0.22 logCS]; P < .001). Large-letter contrast sensitivity was slightly higher after consumption of dark chocolate (mean [SE], 2.05 [0.02] logCS) vs milk chocolate (mean [SE], 2.00 [0.02] logCS; mean improvement, 0.05 logCS [95% CI, 0.00-0.10 logCS]; P = .07). Visual acuity improved slightly after consumption of dark chocolate (mean [SE], -0.22 [0.01] logMAR; visual acuity, approximately 20/12) and milk chocolate (mean [SE], -0.18 [0.01] logMAR; visual acuity, approximately 20/15; mean improvement, 0.04 logMAR [95% CI, 0.02-0.06 logMAR]; P = .05). Composite scores combining results from all tests showed significant improvement after consumption of dark compared with milk chocolate (mean improvement, 0.20 log U [95% CI, 0.10-0.30 log U]; P < .001). Contrast sensitivity and visual acuity were significantly higher 2 hours after consumption of a dark chocolate bar compared with a milk chocolate bar, but the duration of these effects and their influence in real-world performance await further testing. clinicaltrials.gov Identifier: NCT03326934.

Functional Characterization of Tea (Camellia sinensis) MYB4a Transcription Factor Using an Integrative Approach

PubMed Central

Li, Mingzhuo; Li, Yanzhi; Guo, Lili; Gong, Niandi; Pang, Yongzheng; Jiang, Wenbo; Liu, Yajun; Jiang, Xiaolan; Zhao, Lei; Wang, Yunsheng; Xie, De-Yu; Gao, Liping; Xia, Tao

2017-01-01

Green tea (Camellia sinensis, Cs) abundantly produces a diverse array of phenylpropanoid compounds benefiting human health. To date, the regulation of the phenylpropanoid biosynthesis in tea remains to be investigated. Here, we report a cDNA isolated from leaf tissues, which encodes a R2R3-MYB transcription factor. Amino acid sequence alignment and phylogenetic analysis indicate that it is a member of the MYB4-subgroup and named as CsMYB4a. Transcriptional and metabolic analyses show that the expression profile of CsMYB4a is negatively correlated to the accumulation of six flavan-3-ols and other phenolic acids. GFP fusion analysis shows CsMYB4a’s localization in the nucleus. Promoters of five tea phenylpropanoid pathway genes are isolated and characterized to contain four types of AC-elements, which are targets of MYB4 members. Interaction of CsMYB4a and five promoters shows that CsMYB4a decreases all five promoters’ activity. To further characterize its function, CsMYB4a is overexpressed in tobacco plants. The resulting transgenic plants show dwarf, shrinking and yellowish leaf, and early senescence phenotypes. A further genome-wide transcriptomic analysis reveals that the expression levels of 20 tobacco genes involved in the shikimate and the phenylpropanoid pathways are significantly downregulated in transgenic tobacco plants. UPLC-MS and HPLC based metabolic profiling reveals significant reduction of total lignin content, rutin, chlorogenic acid, and phenylalanine in CsMYB4a transgenic tobacco plants. Promoter sequence analysis of the 20 tobacco genes characterizes four types of AC-elements. Further CsMYB4a-AC element and CsMYB4a-promoter interaction analyses indicate that the negative regulation of CsMYB4a on the shikimate and phenylpropanoid pathways in tobacco is via reducing promoter activity. Taken together, all data indicate that CsMYB4a negatively regulates the phenylpropanoid and shikimate pathways. Highlight: A tea (Camellia sinensis) MYB4a is characterized to encode a R2R3-MYB transcription factor. It is shown to repressively control the phenylpropanoid and shikimate pathway. PMID:28659938

The sensory features of a food cue influence its ability to act as an incentive stimulus and evoke dopamine release in the nucleus accumbens core

PubMed Central

Bryan, Myranda A.; Popov, Pavlo; Scarff, Raymond; Carter, Cody; Wright, Erin; Aragona, Brandon J.; Robinson, Terry E.

2016-01-01

The sensory properties of a reward-paired cue (a conditioned stimulus; CS) may impact the motivational value attributed to the cue, and in turn influence the form of the conditioned response (CR) that develops. A cue with multiple sensory qualities, such as a moving lever-CS, may activate numerous neural pathways that process auditory and visual information, resulting in CRs that vary both within and between individuals. For example, CRs include approach to the lever-CS itself (rats that “sign-track”; ST), approach to the location of reward delivery (rats that “goal-track”; GT), or an “intermediate” combination of these behaviors. We found that the multimodal sensory features of the lever-CS were important to the development and expression of sign-tracking. When the lever-CS was covered, and thus could only be heard moving, STs not only continued to approach the lever location but also started to approach the food cup during the CS period. While still predictive of reward, the auditory component of the lever-CS was a much weaker conditioned reinforcer than the visible lever-CS. This plasticity in behavioral responding observed in STs closely resembled behaviors normally seen in rats classified as “intermediates.” Furthermore, the ability of both the lever-CS and the reward-delivery to evoke dopamine release in the nucleus accumbens was also altered by covering the lever—dopamine signaling in STs resembled neurotransmission observed in rats that normally only GT. These data suggest that while the visible lever-CS was attractive, wanted, and had incentive value for STs, when presented in isolation, the auditory component of the cue was simply predictive of reward, lacking incentive salience. Therefore, the specific sensory features of cues may differentially contribute to responding and ensure behavioral flexibility. PMID:27918279

Elucidation and functional characterization of CsPSY and CsUGT promoters in Crocus sativus L.

PubMed Central

Bhat, Archana; Mishra, Sonal; Kaul, Sanjana

2018-01-01

The dried stigmas of Crocus sativus constitute the saffron, which is considered to be the costliest spice of the world. Saffron is valuable for its constituents, which are mainly apocarotenoids. In order to enhance the production of apocarotenoids, it is imperative to understand the regulation of apocarotenoid biosynthetic pathway. In C. sativus, although the pathway has been elucidated, the information regarding the regulation of the pathwaygenes is scanty. During the present investigation, the characterization of promoters regulating the expression of two important genes i.e. CsPSY and CsUGT was performed. We successfully cloned the promoters of both the genes, which were functionally characterized in Crocus sativus and Nicotiana tabaccum. In silico analysis of the promoters demonstrated the presence of several important cis regulatory elements responding tolight, hormonesand interaction with transcription factors (TFs). Further analysis suggested the regulation of CsPSY promoter by Abscisic acid (ABA) and that of CsUGT by Gibberellic acid (GA). In addition, we also observed ABA and GA mediated modulation in the expression of significant TFs and CsPSY and CsUGT transcripts. Overall, the study addresses issues related to regulation of key genes of apocarotenoid pathway in C.sativus. PMID:29634744

Elucidation and functional characterization of CsPSY and CsUGT promoters in Crocus sativus L.

PubMed

Bhat, Archana; Mishra, Sonal; Kaul, Sanjana; Dhar, Manoj K

2018-01-01

The dried stigmas of Crocus sativus constitute the saffron, which is considered to be the costliest spice of the world. Saffron is valuable for its constituents, which are mainly apocarotenoids. In order to enhance the production of apocarotenoids, it is imperative to understand the regulation of apocarotenoid biosynthetic pathway. In C. sativus, although the pathway has been elucidated, the information regarding the regulation of the pathwaygenes is scanty. During the present investigation, the characterization of promoters regulating the expression of two important genes i.e. CsPSY and CsUGT was performed. We successfully cloned the promoters of both the genes, which were functionally characterized in Crocus sativus and Nicotiana tabaccum. In silico analysis of the promoters demonstrated the presence of several important cis regulatory elements responding tolight, hormonesand interaction with transcription factors (TFs). Further analysis suggested the regulation of CsPSY promoter by Abscisic acid (ABA) and that of CsUGT by Gibberellic acid (GA). In addition, we also observed ABA and GA mediated modulation in the expression of significant TFs and CsPSY and CsUGT transcripts. Overall, the study addresses issues related to regulation of key genes of apocarotenoid pathway in C.sativus.

Study of Retinal Nerve Fibre Layer Thickness and Visual Contrast Sensitivity in HIV Positive Individuals.

PubMed

Paul, Rudrajit; Ghosh, Asim K; Nag, Adwaita; Biswas, Shyamapada; Naiya, Britisundar; Mondal, Jayati

2017-06-01

Measurement of Retinal Nerve Fibre Layer Thickness (RNFLT) by Optical Coherence Tomography (OCT) is a sensitive, non invasive and cheap method of detecting early retinal changes in a variety of diseases. In HIV infection, RNFLT is altered and this may have effect on other visual functions like Contrast Sensitivity (CS) and visual acuity. Such ocular pathology can affect the daily life and profession (especially driving) of HIV infected individuals. However, studies on this topic in HIV infected population are rare from India. To study RNFLT, CS and their correlation in a sample of HIV positive Indian population. The present cross-sectional study was done in a tertiary care medical college hospital of Eastern India between May 2016 and September 2016. We did this study on HIV positive subjects with no clinically apparent ocular infection or other pathology. In this study, we have measured the RNFLT using the HRA-OCT Spectralis machine. The CS was tested using a smartphone version of the Pellie-Robson chart. CD4 count, visual acuity and colour vision were also tested. The data was analysed using SPSS version 20.0 for any correlation between these parameters. Pearson coefficient was used for continuous data and Spearman rank correlation was used for categorical data. A p-value <0.05 was considered significant. We had 17 patients, that is 34 eyes. RNFLT loss was found in 21% of the eyes and borderline thinning was found in a further 26%. Predominantly, the temporal quadrant was involved. The mean of log CS was 1.33±0.38. Taking 1.5 as the cut-off value for normalcy, 47% of the eyes tested showed decreased CS. Log CS showed significant correlation with RNFLT of the temporal quadrant only (r=0.37; 95% C.I. 0.041 to 0.631; p=0.02). Temporal RNFLT also showed statistical correlation with the CD4 count. The low CS was also significantly correlated with low visual acuity (r=0.5). In HIV infected persons, subtle ocular changes may occur and this may affect visual functions quite early. Hence, a comprehensive eye check-up should include parameters like CS and OCT.

Relationship between macular pigment and visual function in subjects with early age-related macular degeneration.

PubMed

Akuffo, Kwadwo Owusu; Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

2017-02-01

To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p<0.05) associated with MP across a range of retinal eccentricities, and these statistically significant relationships persisted after controlling for age, sex and cataract grade. BCVA, NEI VFQ-25 score, PRT and mesopic GD were unrelated to MP after controlling for age, sex and cataract grade (p>0.05, for all). MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. ISRCTN13894787. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Visual evoked potential measurement of contrast sensitivity in a case of retinal laser injury reveals visual function loss despite normal acuity

NASA Astrophysics Data System (ADS)

Glickman, Randolph D.; Harrison, Joseph M.; Zwick, Harry; Longbotham, Harold G.; Ballentine, Charles S.; Pierce, Bennie

1996-04-01

Although visual function following retinal laser injuries has traditionally been assessed by measuring visual acuity, this measure only indicates the highest spatial frequency resolvable under high-contrast viewing conditions. Another visual psychophysical parameter is contrast sensitivity (CS), which measures the minimum contrast required for detection of targets over a range of spatial frequencies, and may evaluate visual mechanisms that do not directly subserve acuity. We used the visual evoked potential (VEP) to measure CS in a population of normal subjects and in patients with ophthalmic conditions affecting retinal function, including one patient with a laser injury in the macula. In this patient, the acuity had recovered from

Cued American English: A Variety in the Visual Mode

ERIC Educational Resources Information Center

Portolano, Marlana

2008-01-01

Cued American English (CAE) is a visual variety of English derived from a mode of communication called Cued Speech (CS). CS, or cueing, is a system of communication for use with the deaf, which consists of hand shapes, hand placements, and mouth shapes that signify the phonemic information conventionally conveyed through speech in spoken…

Visual assessment of the cervical vertebral maturation stages: A study of diagnostic accuracy and repeatability.

PubMed

Perinetti, Giuseppe; Caprioglio, Alberto; Contardo, Luca

2014-11-01

To evaluate the diagnostic accuracy and repeatability of the visual assessment of the cervical vertebral maturation (CVM) stages. Ten operators underwent training sessions in visual assessment of CVM staging. Subsequently, they were asked to stage 72 cases equally divided into the six stages. Such assessment was repeated twice in two sessions (T1 and T2) 4 weeks apart. A reference standard for each case was created according to a cephalometric analysis of both the concavities and shapes of the cervical vertebrae. The overall agreement with the reference standard was about 68% for both sessions and 76.9% for intrarater repeatability. The overall kappa coefficients with the reference standard were up to 0.86 for both sessions, and 0.88 for intrarater repeatability. Overall, disagreements one stage and twp stage apart were 23.5% (T1) and 5.1% (T2), respectively. Sensitivity ranged from 53.3% for CS5 (T1) to 99.9% for CS1 (T2), positive predictive values ranged from 52.4% for CS5 (T2) to 94.3% for CS6 (T1), and accuracy ranged from 83.6% for CS4 (T2) to 94.9% for CS1 (T1). Visual assessment of the CVM stages is accurate and repeatable to a satisfactory level. About one in three cases remain misclassified; disagreement is generally limited to one stage and is mostly seen in stages 4 and 5.

Targeted cutaneous delivery of ciclosporin A using micellar nanocarriers and the possible role of inter-cluster regions as molecular transport pathways.

PubMed

Lapteva, Maria; Santer, Verena; Mondon, Karine; Patmanidis, Ilias; Chiriano, Gianpaolo; Scapozza, Leonardo; Gurny, Robert; Möller, Michael; Kalia, Yogeshvar N

2014-12-28

Oral administration of ciclosporin A (CsA) is indicated in the treatment of severe recalcitrant plaque psoriasis. However, CsA is both nephro- and hepatotoxic and its systemic administration also exposes the patient to other severe side effects. Although topical delivery of CsA, targeted directly to psoriatic skin, would offer significant advantages, there are no topical formulations approved for dermatological use. The aim of this work was to formulate CsA loaded polymeric micelles using the biodegradable and biocompatible MPEG-dihexPLA diblock copolymer and to evaluate their potential for delivering the drug selectively into the skin without concomitant transdermal permeation. Micelle formulations were characterised with respect to drug content, size and morphology. Micelle and drug penetration pathways were subsequently visualised with confocal laser scanning microscopy (CLSM) using fluorescein labelled CsA (Fluo-CsA) and Nile-Red (NR) labelled copolymer. Visualisation studies typically use fluorescent dyes as "model drugs"; however, these may have different physicochemical properties to the drug molecule under investigation. Therefore, in this study it was decided to chemically modify CsA and to use this structurally similar fluorescent analogue to visualise molecular distribution and transport pathways. Molecular modelling techniques and experimental determination of log D served as molecular scale and macroscopic methods to compare the lipophilicity of CsA and Fluo-CsA. The spherical, homogeneous and nanometre-scale micelles (with Zav from 25 to 52 nm) increased the aqueous solubility of CsA by 518-fold. Supra-therapeutic amounts of CsA were delivered to human skin (1.4±0.6 μg/cm2, cf. a statistically equivalent 1.1±0.5 μg/cm2 for porcine skin) after application of the formulation with the lowest CsA and copolymer content (1.67±0.03 mg/ml of CsA and 5mg/ml of copolymer) for only 1h without concomitant transdermal permeation. Fluo-CsA was successfully synthesised, characterised and incorporated into fluorescent NR-MPEG-dihexPLA micelles; its conformation was not modified by the addition of fluorescein and its log D, measured from pH4 to 8, was equivalent to that of CsA. Fluo-CsA and NR-MPEG-dihexPLA copolymer were subsequently visualised in skin by CLSM. The images indicated that micelles were preferentially deposited between corneocytes and in the inter-cluster regions (i.e. between the clusters of corneocytes). Fluo-CsA skin penetration was deeper in these structures, suggesting that inter-cluster penetration is probably the preferred transport pathway responsible for the increased cutaneous delivery of CsA. Copyright © 2014 Elsevier B.V. All rights reserved.

Correlation between visual function and refractive, topographic, pachymetric and aberrometric data in eyes with keratoconus

PubMed Central

Bayraktar Bilen, Neslihan; Hepsen, Ibrahim F.; Arce, Carlos G.

2016-01-01

AIM To analyze the relationship between two visual functions and refractive, topographic, pachymetric and aberrometric indicators in eyes with keratoconus. METHODS Corrected distance visual acuity (CDVA), and letter contrast sensitivity (CS) were correlated with refraction, corneal topography, pachymetry, and total corneal wavefront data prospectively in 71 eyes with keratoconus. The topographic indices assessed were simulated keratometry for the flattest and steepest meridians (SimK1 and SimK2), posterior steeper K (Ks), elevation value in best-fit sphere (BFS) maps, squared eccentricity (Є2), aspheric asymmetric index (AAI), pachymetry, thickness progression index (TPI), the amount of pachymetric decentralization (APD), and GalileiTM-keratoconus indices. RESULTS The mean CDVA (expressed as logMAR) were 0.25±0.21. The mean CS was 1.25±0.46. The spherical refraction correlated well with CDVA (r=-0.526, P<0.001). From topographic indices, SRI correlated with CS (r=-0.695), and IAI with CS (r=-0.672) (P<0.001 for all). Root mean square (RMS) was 4.3±1.81 µm, spherical aberration (SA) was -0.4±0.67 µm, vertical and horizontal coma were -2.1±1.47 and -0.4±0.72 µm. All wavefront data (except horizontal coma), AAI, Є2 and maximum BFS correlated significantly with the visual function (P≤0.001 for all). CONCLUSION In this study, CS is more affected than CDVA as a visual function. The quantity and quality of vision is significantly correlated with well-known and new topographic indices. There is not a significant correlation between visual function and pachymetric parameters. The significantly correlated indices can be used in staging keratoconus and to follow the outcome of a treatment. PMID:27588266

Cyclosporin A Inhibits Rotavirus Replication and Restores Interferon-Beta Signaling Pathway In Vitro and In Vivo

PubMed Central

He, Haiyang; Wu, Yuzhang

2013-01-01

Rotavirus (RV) is the most common cause of severe diarrhea among infants and young children. Currently, there is no specific drug available against rotavirus, largely due to the lack of an ideal target molecule which has hampered drug development. Our previous studies have revealed that cyclosporin A (CsA) might be potentially useful as an anti-RV drug. We therefore used both cellular and mouse models to study the immunological safety and effectiveness of CsA as an anti-RV drug. We found that CsA treatment of HT-29 cells before, during, and after viral infection efficiently inhibited Wa strain RV replication and restored IFN-β expression in a HT-29 cell line model. Exploring the underlying mechanisms showed that CsA promoted Interferon Regulatory Factor-5 (IRF-5) expression (a key positive regulator of the type I IFN signaling pathway), but not IRF-1, IRF-3, or IRF-7. Additionally, CsA inhibited SOCS-1 expression (the key negative regulator of IFN-α/β), but not SOCS-2 or SOCS-3. The antiviral effect of CsA was confirmed in an RV-infected neonatal mouse model by evaluation of antigen clearance and assessment of changes in intestinal tissue pathology. Also, no differences in T cell frequency or proliferation between the CsA- and vehicle-treated groups were observed. Thus, both our in vitro and in vivo findings suggest that CsA, through modulating the expression of key regulators in IFN signaling pathway, promote type I IFN-based intracellular innate immunity in RV host cells. These findings suggest that CsA may be a useful candidate to develop a new anti-RV strategy, although further evaluation and characterization of CsA on RV-induced diarrhea are warranted. PMID:23990993

Visual and cognitive predictors of driving safety in Parkinson's disease patients

PubMed Central

Amick, M.M.; Grace, J.; Ott, B.R.

2012-01-01

This study assessed the clinical utility of contrast sensitivity (CS) relative to attention, executive function, and visuospatial abilities for predicting driving safety in participants with Parkinson's disease (PD). Twenty-five, non-demented PD patients completed measures of contrast sensitivity, visuospatial skills, executive functions, and attention. All PD participants also underwent a formal on-road driving evaluation. Of the 25 participants, 11 received a marginal or unsafe rating on the road test. Poorer driving performance was associated with worse performance on measures of CS, visuospatial constructions, set shifting, and attention. While impaired driving was associated with a range of cognitive and visual abilities, only a composite measure of executive functioning and visuospatial abilities, and not CS or attentional skills, predicted driving performance. These findings suggest that neuropsychological tests, which are multifactorial in nature and require visual perception and visual spatial judgments are the most useful screening measures for hazardous driving in PD patients. PMID:17851032

Visual and cognitive predictors of driving safety in Parkinson's disease patients.

PubMed

Amick, M M; Grace, J; Ott, B R

2007-11-01

This study assessed the clinical utility of contrast sensitivity (CS) relative to attention, executive function, and visuospatial abilities for predicting driving safety in participants with Parkinson's disease (PD). Twenty-five, non-demented PD patients completed measures of contrast sensitivity, visuospatial skills, executive functions, and attention. All PD participants also underwent a formal on-road driving evaluation. Of the 25 participants, 11 received a marginal or unsafe rating on the road test. Poorer driving performance was associated with worse performance on measures of CS, visuospatial constructions, set shifting, and attention. While impaired driving was associated with a range of cognitive and visual abilities, only a composite measure of executive functioning and visuospatial abilities, and not CS or attentional skills, predicted driving performance. These findings suggest that neuropsychological tests, which are multifactorial in nature and require visual perception and visual spatial judgments are the most useful screening measures for hazardous driving in PD patients.

Heparanase-driven inflammation from the AGEs-stimulated macrophages changes the functions of glomerular endothelial cells.

PubMed

Xu, Guang; Qin, Qiaojing; Yang, Min; Qiao, Zhongdong; Gu, Yong; Niu, Jianying

2017-02-01

Amounts of macrophages were infiltrated in glomeruli in diabetic nephropathy. Heparanase has been thought to be closely related to proteinuria. Our aims were to determine the effect of heparanase on the inflammation in AGEs-stimulated macrophages and its role on the functions of glomerular endothelial cells (GEnCs). The expression of inflammation cytokines in macrophages were assayed by q-RT PCR, western, and ELISA. Then western was used to measure the expression of RAGE and key proteins in NF-κB pathway in macrophages. The expression of the adherence molecules and tight junction proteins in GEnCs were assessed by western. The adherence of mononuclear cells to GEnCs were observed by HE staining and transendothelial FITC-BSA were tested for the permeability of GEnCs. HPA siRNA and heparanase inhibitor sulodexide could attenuate the increasing inflammatory factors (TNF-α and IL-1β) in AGEs-stimulated macrophages. NF-κB inhibitor PDTC could also decrease the augmented inflammation cytokines through inhibiting the activation of the NF-κB pathway induced by AGEs. The phosphorylation of NF-κB signaling pathway could be also attenuated by HPA siRNA and sulodexide, the same to the receptor of AGEs RAGE. When the macrophage-conditioned culture medium were added to the glomerular endothelial cells, we found HPA siRNA and sulodexide groups could decrease the increasing adherence and permeability of GEnCs induced by AGEs. Heparanase increases the inflammation in AGEs-stimulated macrophages through activating the RAGE-NF-κB pathway. Heparanase driven inflammation from AGEs-stimulated macrophages increases the adherence of GEnCs and augments the permeability of GEnCs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

HRAS mutations in Costello syndrome: detection of constitutional activating mutations in codon 12 and 13 and loss of wild-type allele in malignancy.

PubMed

Estep, Anne L; Tidyman, William E; Teitell, Michael A; Cotter, Philip D; Rauen, Katherine A

2006-01-01

Costello syndrome (CS) is a complex developmental disorder involving characteristic craniofacial features, failure to thrive, developmental delay, cardiac and skeletal anomalies, and a predisposition to develop neoplasia. Based on similarities with other cancer syndromes, we previously hypothesized that CS is likely due to activation of signal transduction through the Ras/MAPK pathway [Tartaglia et al., 2003]. In this study, the HRAS coding region was sequenced for mutations in a large, well-characterized cohort of 36 CS patients. Heterogeneous missense point mutations predicting an amino acid substitution were identified in 33/36 (92%) patients. The majority (91%) had a 34G --> A transition in codon 12. Less frequent mutations included 35G --> C (codon 12) and 37G --> T (codon 13). Parental samples did not have an HRAS mutation supporting the hypothesis of de novo heterogeneous mutations. There is phenotypic variability among patients with a 34G --> A transition. The most consistent features included characteristic facies and skin, failure to thrive, developmental delay, musculoskeletal abnormalities, visual impairment, cardiac abnormalities, and generalized hyperpigmentation. The two patients with 35G --> C had cardiac arrhythmias whereas one patient with a 37G --> T transversion had an enlarged aortic root. Of the patients with a clinical diagnosis of CS, neoplasia was the most consistent phenotypic feature for predicating an HRAS mutation. To gain an understanding of the relationship between constitutional HRAS mutations and malignancy, HRAS was sequenced in an advanced biphasic rhabdomyosarcoma/fibrosarcoma from an individual with a 34G --> A mutation. Loss of the wild-type HRAS allele was observed, suggesting tumorigenesis in CS patients is accompanied by additional somatic changes affecting HRAS. Finally, due to phenotypic overlap between CS and cardio-facio-cutaneous (CFC) syndromes, the HRAS coding region was sequenced in a well-characterized CFC cohort. No mutations were found which support a distinct genetic etiology between CS and CFC syndromes. (c) 2005 Wiley-Liss, Inc.

Diagnostic Pathway with Multiparametric Magnetic Resonance Imaging Versus Standard Pathway: Results from a Randomized Prospective Study in Biopsy-naïve Patients with Suspected Prostate Cancer.

PubMed

Porpiglia, Francesco; Manfredi, Matteo; Mele, Fabrizio; Cossu, Marco; Bollito, Enrico; Veltri, Andrea; Cirillo, Stefano; Regge, Daniele; Faletti, Riccardo; Passera, Roberto; Fiori, Cristian; De Luca, Stefano

2017-08-01

An approach based on multiparametric magnetic resonance imaging (mpMRI) might increase the detection rate (DR) of clinically significant prostate cancer (csPCa). To compare an mpMRI-based pathway with the standard approach for the detection of prostate cancer (PCa) and csPCa. Between November 2014 and April 2016, 212 biopsy-naïve patients with suspected PCa (prostate specific antigen level ≤15 ng/ml and negative digital rectal examination results) were included in this randomized clinical trial. Patients were randomized into a prebiopsy mpMRI group (arm A, n=107) or a standard biopsy (SB) group (arm B, n=105). In arm A, patients with mpMRI evidence of lesions suspected for PCa underwent mpMRI/transrectal ultrasound fusion software-guided targeted biopsy (TB) (n=81). The remaining patients in arm A (n=26) with negative mpMRI results and patients in arm B underwent 12-core SB. The primary end point was comparison of the DR of PCa and csPCa between the two arms of the study; the secondary end point was comparison of the DR between TB and SB. The overall DRs were higher in arm A versus arm B for PCa (50.5% vs 29.5%, respectively; p=0.002) and csPCa (43.9% vs 18.1%, respectively; p<0.001). Concerning the biopsy approach, that is, TB in arm A, SB in arm A, and SB in arm B, the overall DRs were significantly different for PCa (60.5% vs 19.2% vs 29.5%, respectively; p<0.001) and for csPCa (56.8% vs 3.8% vs 18.1%, respectively; p<0.001). The reproducibility of the study could have been affected by the single-center nature. A diagnostic pathway based on mpMRI had a higher DR than the standard pathway in both PCa and csPCa. In this randomized trial, a pathway for the diagnosis of prostate cancer based on multiparametric magnetic resonance imaging (mpMRI) was compared with the standard pathway based on random biopsy. The mpMRI-based pathway had better performance than the standard pathway. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The Impact of Supplemental Antioxidants on Visual Function in Nonadvanced Age-Related Macular Degeneration: A Head-to-Head Randomized Clinical Trial.

PubMed

Akuffo, Kwadwo Owusu; Beatty, Stephen; Peto, Tunde; Stack, Jim; Stringham, Jim; Kelly, David; Leung, Irene; Corcoran, Laura; Nolan, John M

2017-10-01

The purpose of this study was to evaluate the impact of supplemental macular carotenoids (including versus not including meso-zeaxanthin) in combination with coantioxidants on visual function in patients with nonadvanced age-related macular degeneration. In this study, 121 participants were randomly assigned to group 1 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc and an addition of 10 mg meso-zeaxanthin; n = 60) or group 2 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of zinc; n = 61). Visual function was assessed using best-corrected visual acuity, contrast sensitivity (CS), glare disability, retinal straylight, photostress recovery time, reading performance, and the National Eye Institute Visual Function Questionnaire-25. Macular pigment was measured using customized heterochromatic flicker photometry. There was a statistically significant improvement in the primary outcome measure (letter CS at 6 cycles per degree [6 cpd]) over time (P = 0.013), and this observed improvement was statistically comparable between interventions (P = 0.881). Statistically significant improvements in several secondary outcome visual function measures (letter CS at 1.2 and 2.4 cpd; mesopic and photopic CS at all spatial frequencies; mesopic glare disability at 1.5, 3, and 6 cpd; photopic glare disability at 1.5, 3, 6, and 12 cpd; photostress recovery time; retinal straylight; mean and maximum reading speed) were also observed over time (P < 0.05, for all), and were statistically comparable between interventions (P > 0.05, for all). Statistically significant increases in macular pigment at all eccentricities were observed over time (P < 0.0005, for all), and the degree of augmentation was statistically comparable between interventions (P > 0.05). Antioxidant supplementation in patients with nonadvanced age-related macular degeneration results in significant increases in macular pigment and improvements in CS and other measures of visual function. (Clinical trial, http://www.isrctn.com/ISRCTN13894787).

Predicting Visual Disability in Glaucoma With Combinations of Vision Measures.

PubMed

Lin, Stephanie; Mihailovic, Aleksandra; West, Sheila K; Johnson, Chris A; Friedman, David S; Kong, Xiangrong; Ramulu, Pradeep Y

2018-04-01

We characterized vision in glaucoma using seven visual measures, with the goals of determining the dimensionality of vision, and how many and which visual measures best model activity limitation. We analyzed cross-sectional data from 150 older adults with glaucoma, collecting seven visual measures: integrated visual field (VF) sensitivity, visual acuity, contrast sensitivity (CS), area under the log CS function, color vision, stereoacuity, and visual acuity with noise. Principal component analysis was used to examine the dimensionality of vision. Multivariable regression models using one, two, or three vision tests (and nonvisual predictors) were compared to determine which was best associated with Rasch-analyzed Glaucoma Quality of Life-15 (GQL-15) person measure scores. The participants had a mean age of 70.2 and IVF sensitivity of 26.6 dB, suggesting mild-to-moderate glaucoma. All seven vision measures loaded similarly onto the first principal component (eigenvectors, 0.220-0.442), which explained 56.9% of the variance in vision scores. In models for GQL scores, the maximum adjusted- R 2 values obtained were 0.263, 0.296, and 0.301 when using one, two, and three vision tests in the models, respectively, though several models in each category had similar adjusted- R 2 values. All three of the best-performing models contained CS. Vision in glaucoma is a multidimensional construct that can be described by several variably-correlated vision measures. Measuring more than two vision tests does not substantially improve models for activity limitation. A sufficient description of disability in glaucoma can be obtained using one to two vision tests, especially VF and CS.

Interaction between cysteine synthase and serine O-acetyltransferase proteins and their stage specific expression in Leishmania donovani.

PubMed

Singh, Kuljit; Singh, Krishn Pratap; Equbal, Asif; Suman, Shashi S; Zaidi, Amir; Garg, Gaurav; Pandey, Krishna; Das, Pradeep; Ali, Vahab

2016-12-01

Leishmania possess a unique trypanothione redox metabolism with undebated roles in protection from oxidative damage and drug resistance. The biosynthesis of trypanothione depends on l-cysteine bioavailability which is regulated by cysteine biosynthesis pathway. The de novo cysteine biosynthesis pathway is comprised of serine O-acetyltransferase (SAT) and cysteine synthase (CS) enzymes which sequentially mediate two consecutive steps of cysteine biosynthesis, and is absent in mammalian host. However, despite the apparent dependency of redox metabolism on cysteine biosynthesis pathway, the role of SAT and CS in redox homeostasis has been unexplored in Leishmania parasites. Herein, we have characterized CS and SAT to investigate their interaction and relative abundance of these proteins in promastigote vs. amastigote growth stages of L. donovani. CS and SAT genes of L. donovani (LdCS and LdSAT) were cloned, expressed, and fusion proteins purified to homogeneity with affinity column chromatography. Purified LdCS contains PLP as cofactor and showed optimum enzymatic activity at pH 7.5. Enzyme kinetics showed that LdCS catalyses the synthesis of cysteine using O-acetylserine and sulfide with a K m of 15.86 mM and 0.17 mM, respectively. Digitonin fractionation and indirect immunofluorescence microscopy showed that LdCS and LdSAT are localized in the cytoplasm of promastigotes. Size exclusion chromatography, co-purification, pull down and immuno-precipitation assays demonstrated a stable complex formation between LdCS and LdSAT proteins. Furthermore, LdCS and LdSAT proteins expression/activity was upregulated in amastigote growth stage of the parasite. Thus, the stage specific differential expression of LdCS and LdSAT suggests that it may have a role in the redox homeostasis of Leishmania. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Transcriptomic Analysis of Lung Tissue from Cigarette Smoke-Induced Emphysema Murine Models and Human Chronic Obstructive Pulmonary Disease Show Shared and Distinct Pathways.

PubMed

Yun, Jeong H; Morrow, Jarrett; Owen, Caroline A; Qiu, Weiliang; Glass, Kimberly; Lao, Taotao; Jiang, Zhiqiang; Perrella, Mark A; Silverman, Edwin K; Zhou, Xiaobo; Hersh, Craig P

2017-07-01

Although cigarette smoke (CS) is the primary risk factor for chronic obstructive pulmonary disease (COPD), the underlying molecular mechanisms for the significant variability in developing COPD in response to CS are incompletely understood. We performed lung gene expression profiling of two different wild-type murine strains (C57BL/6 and NZW/LacJ) and two genetic models with mutations in COPD genome-wide association study genes (HHIP and FAM13A) after 6 months of chronic CS exposure and compared the results to human COPD lung tissues. We identified gene expression patterns that correlate with severity of emphysema in murine and human lungs. Xenobiotic metabolism and nuclear erythroid 2-related factor 2-mediated oxidative stress response were commonly regulated molecular response patterns in C57BL/6, Hhip +/- , and Fam13a -/- murine strains exposed chronically to CS. The CS-resistant Fam13a -/- mouse and NZW/LacJ strain revealed gene expression response pattern differences. The Fam13a -/- strain diverged in gene expression compared with C57BL/6 control only after CS exposure. However, the NZW/LacJ strain had a unique baseline expression pattern, enriched for nuclear erythroid 2-related factor 2-mediated oxidative stress response and xenobiotic metabolism, and converged to a gene expression pattern similar to the more susceptible wild-type C57BL/6 after CS exposure. These results suggest that distinct molecular pathways may account for resistance to emphysema. Surprisingly, there were few genes commonly modulated in mice and humans. Our study suggests that gene expression responses to CS may be largely species and model dependent, yet shared pathways could provide biologically significant insights underlying individual susceptibility to CS.

Contrast sensitivity and its determinants in people with diabetes: SN-DREAMS-II, Report No 6

PubMed Central

Gella, L; Raman, R; Pal, S S; Ganesan, S; Sharma, T

2017-01-01

Purpose To assess contrast sensitivity (CS) and to elucidate the factors associated with CS among subjects with type 2 diabetes in a cross-sectional population-based study. Patients and methods Subjects were recruited from a follow-up cohort, Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular genetics Study (SN-DREAMS II). Of 958 subjects who were followed up in SN-DREAMS II, a subset of 653 subjects was included in the analysis. All subjects underwent a comprehensive eye examination, which included CS assessment using the Pelli–Robson chart. The cross-sectional association between CS and independent variables was assessed using stepwise linear regression analysis. A P-value of <0.05 was considered statistically significant. Results The mean age of the study sample was 58.7±9.41 (44–87) years. Mean CS of the study sample was 1.32±0.20 (range: 0–1.65) log units. CS was negatively and significantly correlated with age, duration of diabetes, hemoglobin level, vibration perception threshold (VPT) value, albuminuria, best corrected visual acuity (BCVA), refractive error, total error score (TEM) of FM 100 hue test, and mean retinal sensitivity. In multiple regression analysis, after adjusting for all the related factors, CS was significantly associated with BCVA (β=−0.575; P<0.001), VPT (β=−0.003; P=0.010), severity of cataract (β=−0.018; P=0.032), diabetic retinopathy (β=−0.016; P=0.019), and age (β=−0.002; P=0.029). These factors explained about 29.3% of the variation in CS. Conclusion Among the factors evaluated, differences in BCVA were associated with the largest predicted differences in CS. This association of CS with visual acuity highlights the important role of visual assessment in type 2 diabetes. PMID:27858934

Keratinocyte secretion of cyclophilin B via the constitutive pathway is regulated through its cyclosporin-binding site.

PubMed

Fearon, Paula; Lonsdale-Eccles, Ann A; Ross, O Kehinde; Todd, Carole; Sinha, Aparna; Allain, Fabrice; Reynolds, Nick J

2011-05-01

Cyclophilin B (CypB) is an endoplasmic reticulum (ER)-resident member of the cyclophilin family of proteins that bind cyclosporin A (CsA). We report that as in other cell types, CypB trafficked from the ER and was secreted by keratinocytes into the media in response to CsA. Concentrations as low as 1 pM of CsA induced secretion of CypB. Using brefeldin A, we showed that CypB is secreted from keratinocytes via the constitutive secretory pathway. We defined that substitution of tryptophan residue 128 in the CsA-binding site of CypB with alanine resulted in dissociation of CypB(W128A)-green fluorescent protein (GFP) from the ER. Photobleaching studies revealed a significant reduction in the diffusible mobility of CypB(W128A)-GFP compared with CypB(WT)-GFP, consistent with redistribution of CypB(W128A)-GFP into secretory vesicles disconnected from the ER/Golgi network. Furthermore, CsA significantly decreased the mobility of CypB(WT)-GFP but not CypB(W128A)-GFP. These studies demonstrate that therapeutically relevant concentrations of CsA regulate secretion of CypB by keratinocytes, and that a key residue within the CsA-binding site of CypB controls retention of CypB within the ER and regulates entry into the secretory pathway. As keratinocytes express CypB receptors (CD147) and CypB exhibits chemotactic properties, these data have implications for the therapeutic effects of CsA in inflammatory skin disease.

Keratinocyte Secretion of Cyclophilin B via the Constitutive Pathway Is Regulated through Its Cyclosporin-Binding Site

PubMed Central

Fearon, Paula; Lonsdale-Eccles, Ann A; Ross, O Kehinde; Todd, Carole; Sinha, Aparna; Allain, Fabrice; Reynolds, Nick J

2011-01-01

Cyclophilin B (CypB) is an endoplasmic reticulum (ER)-resident member of the cyclophilin family of proteins that bind cyclosporin A (CsA). We report that as in other cell types, CypB trafficked from the ER and was secreted by keratinocytes into the media in response to CsA. Concentrations as low as 1 p of CsA induced secretion of CypB. Using brefeldin A, we showed that CypB is secreted from keratinocytes via the constitutive secretory pathway. We defined that substitution of tryptophan residue 128 in the CsA-binding site of CypB with alanine resulted in dissociation of CypBW128A-green fluorescent protein (GFP) from the ER. Photobleaching studies revealed a significant reduction in the diffusible mobility of CypBW128A-GFP compared with CypBWT-GFP, consistent with redistribution of CypBW128A-GFP into secretory vesicles disconnected from the ER/Golgi network. Furthermore, CsA significantly decreased the mobility of CypBWT-GFP but not CypBW128A-GFP. These studies demonstrate that therapeutically relevant concentrations of CsA regulate secretion of CypB by keratinocytes, and that a key residue within the CsA-binding site of CypB controls retention of CypB within the ER and regulates entry into the secretory pathway. As keratinocytes express CypB receptors (CD147) and CypB exhibits chemotactic properties, these data have implications for the therapeutic effects of CsA in inflammatory skin disease. PMID:21270823

Driving habits in older patients with central vision loss.

PubMed

Sengupta, Sabyasachi; van Landingham, Suzanne W; Solomon, Sharon D; Do, Diana V; Friedman, David S; Ramulu, Pradeep Y

2014-03-01

To determine if central visual loss is associated with driving cessation, driving restriction, or other-driver preference. Cross-sectional study. Sixty-four subjects with bilateral visual loss (<20/32 in better eye) or severe unilateral visual loss (<20/200) from age-related macular degeneration (AMD) and 58 normally sighted controls between 60 and 80 years of age. Participants self-reported driving habits. Other-driver preference was defined as preferring that another drive when there is more than 1 driver in the car. Subjects reporting 2 or more driving limitations were considered to have restricted their driving. Self-reported driving cessation, other-driver preference, and driving restriction. Age-related macular degeneration subjects were older (74.7 vs. 69.7 years), had worse visual acuity (VA; mean better-eye VA, 0.43 vs. 0.08 logarithm of minimum angle of resolution [logMAR]) and contrast sensitivity (CS; 1.4 vs. 1.9 log units of CS [logCS]), and were more likely to be white when compared with controls (P<0.001 for all). Drivers with AMD-related vision loss were more likely to avoid driving over longer distances, beyond 1 hour, at night, and in unfamiliar conditions (P < 0.05 for all). In multivariate models, driving cessation was associated with worse better-eye VA (odds ratio [OR], 1.5 per 1-line decrement in VA; P<0.001) and worse binocular CS (OR, 1.36 per 0.1 logCS increment; P = 0.005); however, AMD group status was not associated with driving cessation (OR, 1.9; P = 0.35). Factors predicting driving restriction were AMD (OR, 9.0; P = 0.004), worse vision (OR, 2.5 per line of VA loss; P<0.001), lower CS (OR, 2.2 per 0.1-logCS increment; P<0.001), and female gender (OR, 27.9; P = 0.002). Other-driver preference was more common with worse vision (OR, 1.6 per 0.1-logMAR increment; P = 0.003), female gender (OR, 4.5; P = 0.02), and being married (OR, 3.8; P = 0.04). Most patients with AMD-related central vision loss continue to drive, but demonstrate significant driving restrictions, especially with more severe VA and CS loss. Future work should determine which driving adaptations the visually impaired best balance safety and independence. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis by suppressing VEGFR-2 signaling pathway.

PubMed

Tang, Ning; Shi, Lei; Yu, Zhenlong; Dong, Peipei; Wang, Chao; Huo, Xiaokui; Zhang, Baojing; Huang, Shanshan; Deng, Sa; Liu, Kexin; Ma, Tonghui; Wang, Xiaobo; Wu, Lijun; Ma, Xiao-Chi

2016-01-19

Gamabufotalin (CS-6), a main active compound isolated from Chinese medicine Chansu, has been shown to strongly inhibit cancer cell growth and inflammatory response. However, its effects on angiogenesis have not been known yet. Here, we sought to determine the biological effects of CS-6 on signaling mechanisms during angiogenesis. Our present results fully demonstrate that CS-6 could significantly inhibit VEGF triggered HUVECs proliferation, migration, invasion and tubulogenesis in vitro and blocked vascularization in Matrigel plugs impregnated in C57/BL6 mice as well as reduced vessel density in human lung tumor xenograft implanted in nude mice. Computer simulations revealed that CS-6 interacted with the ATP-binding sites of VEGFR-2 using molecular docking. Furthermore, western blot analysis indicated that CS-6 inhibited VEGF-induced phosphorylation of VEGFR-2 kinase and suppressed the activity of VEGFR-2-mediated signaling cascades. Therefore, our studies demonstrated that CS-6 inhibited angiogenesis by inhibiting the activation of VEGFR-2 signaling pathways and CS-6 could be a potential candidate in angiogenesis-related disease therapy.

Functional characterization of proanthocyanidin pathway enzymes from tea and their application for metabolic engineering.

PubMed

Pang, Yongzhen; Abeysinghe, I Sarath B; He, Ji; He, Xianzhi; Huhman, David; Mewan, K Mudith; Sumner, Lloyd W; Yun, Jianfei; Dixon, Richard A

2013-03-01

Tea (Camellia sinensis) is rich in specialized metabolites, especially polyphenolic proanthocyanidins (PAs) and their precursors. To better understand the PA pathway in tea, we generated a complementary DNA library from leaf tissue of the blister blight-resistant tea cultivar TRI2043 and functionally characterized key enzymes responsible for the biosynthesis of PA precursors. Structural genes encoding enzymes involved in the general phenylpropanoid/flavonoid pathway and the PA-specific branch pathway were well represented in the library. Recombinant tea leucoanthocyanidin reductase (CsLAR) expressed in Escherichia coli was active with leucocyanidin as substrate to produce the 2R,3S-trans-flavan-ol (+)-catechin in vitro. Two genes encoding anthocyanidin reductase, CsANR1 and CsANR2, were also expressed in E. coli, and the recombinant proteins exhibited similar kinetic properties. Both converted cyanidin to a mixture of (+)-epicatechin and (-)-catechin, although in different proportions, indicating that both enzymes possess epimerase activity. These epimers were unexpected based on the belief that tea PAs are made from (-)-epicatechin and (+)-catechin. Ectopic expression of CsANR2 or CsLAR led to the accumulation of low levels of PA precursors and their conjugates in Medicago truncatula hairy roots and anthocyanin-overproducing tobacco (Nicotiana tabacum), but levels of oligomeric PAs were very low. Surprisingly, the expression of CsLAR in tobacco overproducing anthocyanin led to the accumulation of higher levels of epicatechin and its glucoside than of catechin, again highlighting the potential importance of epimerization in flavan-3-ol biosynthesis. These data provide a resource for understanding tea PA biosynthesis and tools for the bioengineering of flavanols.

The Neural Basis of Speech Perception through Lipreading and Manual Cues: Evidence from Deaf Native Users of Cued Speech

PubMed Central

Aparicio, Mario; Peigneux, Philippe; Charlier, Brigitte; Balériaux, Danielle; Kavec, Martin; Leybaert, Jacqueline

2017-01-01

We present here the first neuroimaging data for perception of Cued Speech (CS) by deaf adults who are native users of CS. CS is a visual mode of communicating a spoken language through a set of manual cues which accompany lipreading and disambiguate it. With CS, sublexical units of the oral language are conveyed clearly and completely through the visual modality without requiring hearing. The comparison of neural processing of CS in deaf individuals with processing of audiovisual (AV) speech in normally hearing individuals represents a unique opportunity to explore the similarities and differences in neural processing of an oral language delivered in a visuo-manual vs. an AV modality. The study included deaf adult participants who were early CS users and native hearing users of French who process speech audiovisually. Words were presented in an event-related fMRI design. Three conditions were presented to each group of participants. The deaf participants saw CS words (manual + lipread), words presented as manual cues alone, and words presented to be lipread without manual cues. The hearing group saw AV spoken words, audio-alone and lipread-alone. Three findings are highlighted. First, the middle and superior temporal gyrus (excluding Heschl’s gyrus) and left inferior frontal gyrus pars triangularis constituted a common, amodal neural basis for AV and CS perception. Second, integration was inferred in posterior parts of superior temporal sulcus for audio and lipread information in AV speech, but in the occipito-temporal junction, including MT/V5, for the manual cues and lipreading in CS. Third, the perception of manual cues showed a much greater overlap with the regions activated by CS (manual + lipreading) than lipreading alone did. This supports the notion that manual cues play a larger role than lipreading for CS processing. The present study contributes to a better understanding of the role of manual cues as support of visual speech perception in the framework of the multimodal nature of human communication. PMID:28424636

Effect of experimental glaucoma on the non-image forming visual system.

PubMed

de Zavalía, Nuria; Plano, Santiago A; Fernandez, Diego C; Lanzani, María Florencia; Salido, Ezequiel; Belforte, Nicolás; Sarmiento, María I Keller; Golombek, Diego A; Rosenstein, Ruth E

2011-06-01

Glaucoma is a leading cause of blindness worldwide, characterized by retinal ganglion cell degeneration and damage to the optic nerve. We investigated the non-image forming visual system in an experimental model of glaucoma in rats induced by weekly injections of chondroitin sulphate (CS) in the eye anterior chamber. Animals were unilaterally or bilaterally injected with CS or vehicle for 6 or 10 weeks. In the retinas from eyes injected with CS, a similar decrease in melanopsin and Thy-1 levels was observed. CS injections induced a similar decrease in the number of melanopsin-containing cells and superior collicular retinal ganglion cells. Experimental glaucoma induced a significant decrease in the afferent pupil light reflex. White light significantly decreased nocturnal pineal melatonin content in control and glaucomatous animals, whereas blue light decreased this parameter in vehicle- but not in CS-injected animals. A significant decrease in light-induced c-Fos expression in the suprachiasmatic nuclei was observed in glaucomatous animals. General rhythmicity and gross entrainment appear to be conserved, but glaucomatous animals exhibited a delayed phase angle with respect to lights off and a significant increase in the percentage of diurnal activity. These results indicate the glaucoma induced significant alterations in the non-image forming visual system. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Functional Characterization of Proanthocyanidin Pathway Enzymes from Tea and Their Application for Metabolic Engineering1[W][OA

PubMed Central

Pang, Yongzhen; Abeysinghe, I. Sarath B.; He, Ji; He, Xianzhi; Huhman, David; Mewan, K. Mudith; Sumner, Lloyd W.; Yun, Jianfei; Dixon, Richard A.

2013-01-01

Tea (Camellia sinensis) is rich in specialized metabolites, especially polyphenolic proanthocyanidins (PAs) and their precursors. To better understand the PA pathway in tea, we generated a complementary DNA library from leaf tissue of the blister blight-resistant tea cultivar TRI2043 and functionally characterized key enzymes responsible for the biosynthesis of PA precursors. Structural genes encoding enzymes involved in the general phenylpropanoid/flavonoid pathway and the PA-specific branch pathway were well represented in the library. Recombinant tea leucoanthocyanidin reductase (CsLAR) expressed in Escherichia coli was active with leucocyanidin as substrate to produce the 2R,3S-trans-flavan-ol (+)-catechin in vitro. Two genes encoding anthocyanidin reductase, CsANR1 and CsANR2, were also expressed in E. coli, and the recombinant proteins exhibited similar kinetic properties. Both converted cyanidin to a mixture of (+)-epicatechin and (−)-catechin, although in different proportions, indicating that both enzymes possess epimerase activity. These epimers were unexpected based on the belief that tea PAs are made from (−)-epicatechin and (+)-catechin. Ectopic expression of CsANR2 or CsLAR led to the accumulation of low levels of PA precursors and their conjugates in Medicago truncatula hairy roots and anthocyanin-overproducing tobacco (Nicotiana tabacum), but levels of oligomeric PAs were very low. Surprisingly, the expression of CsLAR in tobacco overproducing anthocyanin led to the accumulation of higher levels of epicatechin and its glucoside than of catechin, again highlighting the potential importance of epimerization in flavan-3-ol biosynthesis. These data provide a resource for understanding tea PA biosynthesis and tools for the bioengineering of flavanols. PMID:23288883

An essential role of a FoxD gene in notochord induction in Ciona embryos.

PubMed

Imai, Kaoru S; Satoh, Nori; Satou, Yutaka

2002-07-01

A key issue for understanding the early development of the chordate body plan is how the endoderm induces notochord formation. In the ascidian Ciona, nuclear accumulation of beta-catenin is the first step in the process of endoderm specification. We show that nuclear accumulation of beta-catenin directly activates the gene (Cs-FoxD) for a winged helix/forkhead transcription factor and that this gene is expressed transiently at the 16- and 32-cell stages in endodermal cells. The function of Cs-FoxD, however, is not associated with differentiation of the endoderm itself but is essential for notochord differentiation or induction. In addition, it is likely that the inductive signal that appears to act downstream of Cs-FoxD does not act over a long range. It has been suggested that FGF or Notch signal transduction pathway mediates ascidian notochord induction. Our previous study suggests that Cs-FGF4/6/9 is partially involved in the notochord induction. The present experimental results suggest that the expression and function of Cs-FGF4/6/9 and Cs-FoxD are not interdependent, and that the Notch pathway is involved in B-line notochord induction downstream of Cs-FoxD.

Experimental approaches to assessing the impact of a cesium chloride radiological dispersal device

USGS Publications Warehouse

Lee, S.; Gibb, Snyder E.; Barzyk, J.; McGee, J.; Koenig, A.

2008-01-01

The US EPA, as a part of the Chemical, Biological, Radiological-Nuclear, and Explosives (CBRNE) Research and Technology Initiative (CRTI) project team, is currently working to assess the impacts of an urban radiological dispersion device (RDD) and to develop containment and decontamination strategies. Three efforts in this area are currently underway: development of a laboratory-scale cesium chloride deposition method to mimic a RDD; assessment of cesium (Cs) penetration depth and pathways in urban materials using two dimensional (2-D) mapping laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS); and experimental determination of distribution coefficients (kd) for Cs in water-building material systems. It is critical that, when performing laboratory-scale experiments to assess the fate of Cs from an RDD, the Cs particle deposition method mimics the RDD deposition. Once Cs particles are deposited onto urban surfaces, 2-D mapping of Cs concentrations using LA-ICP-MS is a critical tool for determining Cs transport pathways through these materials. Lastly, distribution coefficients are critical for understanding the transport of Cs in urban settings when direct measurements of its penetration depth are unavailable. An assessment of the newly developed deposition method along with preliminary results from the penetration experiments are presented in this paper.

Evaluation of the Parent-Implemented Communication Strategies (PiCS) Project Using the Multiattribute Utility (MAU) Approach

ERIC Educational Resources Information Center

Stoner, Julia B.; Meadan, Hedda; Angell, Maureen E.; Daczewitz, Marcus

2012-01-01

We conducted a multiattribute utility (MAU) evaluation to assess the Parent-Implemented Communication Strategies (PiCS) project which was funded by the Institute of Education Sciences (IES). In the PiCS project parents of young children with developmental disabilities are trained and coached in their homes on naturalistic and visual teaching…

Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway.

PubMed

Ye, Bai-Liang; Zheng, Ru; Ruan, Xiao-Jiao; Zheng, Zhi-Hai; Cai, Hua-Jie

2018-01-01

Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer. The chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them. The FA-CS-DOX nano-particles were irregular and spherical particles around 30-40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway. Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluating visual function in cataract.

PubMed

Elliott, D B

1993-11-01

This paper reviews recent research on the evaluation of visual function in cataract. Visual impairment in cataract is principally caused by increased intraocular forward light scatter. It is assumed that visual acuity (VA) measurements assess the impact of narrow angle light scatter. This also makes the measurement of high spatial frequency contrast sensitivity (CS) unnecessary. However, VA measurements alone are an inadequate assessment of visual impairment in some patients with cataract. In addition, it is suggested that a measurement of wide-angle light scatter is required. This can be evaluated directly using the van den Berg Straylightmeter, or indirectly using low spatial frequency CS or disability glare (DG) tests. The following are discussed: (1) the relative usefulness of these tests; (2) how they can be incorporated into the decision as to when to extract a cataract; and (3) the importance of considering binocular visual function.

Correlation between observation task performance and visual acuity, contrast sensitivity and environmental light in a simulated maritime study.

PubMed

Koefoed, Vilhelm F; Assmuss, Jörg; Høvding, Gunnar

2018-03-25

To examine the relevance of visual acuity (VA) and index of contrast sensitivity (ICS) as predictors for visual observation task performance in a maritime environment. Sixty naval cadets were recruited to a study on observation tasks in a simulated maritime environment under three different light settings. Their ICS were computed based on contrast sensitivity (CS) data recorded by Optec 6500 and CSV-1000E CS tests. The correlation between object identification distance and VA/ICS was examined by stepwise linear regression. The object detection distance was significantly correlated to the level of environmental light (p < 0.001), but not to the VA or ICS recorded in the test subjects. Female cadets had a significantly shorter target identification range than the male cadets. Neither CS nor VA were found to be significantly correlated to observation task performance. This apparent absence of proven predictive value of visual parameters for observation tasks in a maritime environment may presumably be ascribed to the normal and uniform visual capacity in all our study subjects. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Contrast sensitivity to spatial gratings in moderate and dim light conditions in patients with diabetes in the absence of diabetic retinopathy.

PubMed

Safi, Sare; Rahimi, Anoushiravan; Raeesi, Afsaneh; Safi, Hamid; Aghazadeh Amiri, Mohammad; Malek, Mojtaba; Yaseri, Mehdi; Haeri, Mohammad; Middleton, Frank A; Solessio, Eduardo; Ahmadieh, Hamid

2017-01-01

To evaluate the ability of contrast sensitivity (CS) to discriminate loss of visual function in diabetic subjects with no clinical signs of retinopathy relative to that of normal subjects. In this prospective cross-sectional study, we measured CS in 46 diabetic subjects with a mean age of 48±6 years, a best-corrected visual acuity of 20/20 and no signs of diabetic retinopathy. The CS in these subjects was compared with CS measurements in 46 normal control subjects at four spatial frequencies (3, 6, 12, 18 cycles per degree) under moderate (500 lux) and dim (less than 2 lux) background light conditions. CS was approximately 0.16 log units lower in patients with diabetes relative to controls both in moderate and in dim background light conditions. Logistic regression classification and receiver operating characteristic curve analysis indicated that CS analysis using two light conditions was more accurate (0.78) overall compared with CS analysis using only a single illumination condition (accuracy values were 0.67 and 0.70 in moderate and dim light conditions, respectively). Our results showed that patients with diabetes without clinical signs of retinopathy exhibit a uniform loss in CS at all spatial frequencies tested. Measuring the loss in CS at two spatial frequencies (3 and 6 cycles per degree) and two light conditions (moderate and dim) is sufficiently robust to classify diabetic subjects with no retinopathy versus control subjects.

A Phosphatidylinositol 3-kinase-regulated Akt-independent signaling promotes cigarette smoke-induced FRA-1 expression.

PubMed

Zhang, Qin; Adiseshaiah, Pavan; Kalvakolanu, Dhananjaya V; Reddy, Sekhar P

2006-04-14

The FRA-1 proto-oncogene is overexpressed in a variety of human tumors and is known to up-regulate the expression of genes involved in tumor progression and invasion. The phosphatidylinositol 3-kinase (PI3K)-Akt pathway is also known to regulate these cellular processes. More importantly, respiratory toxicants and carcinogens activate both the PI3K-Akt pathway and FRA-1 expression in human bronchial epithelial (HBE) cells. In this study we investigated a potential link between the PI3K-Akt pathway and the cigarette smoke (CS)-stimulated epidermal growth factor receptor-mediated FRA-1 induction in non-oncogenic HBE cells. Treatment of cells with LY294002, an inhibitor of the PI3K-Akt pathway, completely blocked CS-induced FRA-1 expression. Surprisingly pharmacological inhibition of Akt had no significant effect on CS-induced FRA-1 expression. Likewise the inhibition of protein kinase C zeta, which is a known downstream effector of PI3K, did not alter FRA-1 expression. We found that the PI3K through p21-activated kinase 1 regulates FRA-1 proto-oncogene induction by CS and the subsequent activation of the Elk1 and cAMP-response element-binding protein transcription factors that are bound to the promoter in HBE cells.

Hydrogen bonding effects on the reorganization energy for photoinduced charge separation reaction between porphyrin and quinone studied by nanosecond laser flash photolysis.

PubMed

Yago, Tomoaki; Gohdo, Masao; Wakasa, Masanobu

2010-02-25

Alcohol concentration dependences of photoinduced charge separation (CS) reaction of zinc tetraphenyl-porphyrin (ZnTPP) and duroquinone (DQ) were investigated in benzonitrile by a nanosecond laser flash photolysis technique. The photoinduced CS reaction was accelerated by the addition of alcohols, whereas the addition of acetonitrile caused little effect on the CS reactions. The simple theory was developed to calculate an increase in reorganization energies induced by the hydrogen bonding interactions between DQ and alcohols using the chemical equilibrium constants for the hydrogen bonding complexes through the concerted pathway and the stepwise one. The experimental results were analyzed by using the Marcus equation where we took into account the hydrogen bonding effects on the reorganization energy and the reaction free energy for the CS reaction. The observed alcohol concentration dependence of the CS reaction rates was well explained by the formation of the hydrogen bonding complexes through the concerted pathway, demonstrating the increase in the reorganization energy by the hydrogen bonding interactions.

Using the Freiburg Acuity and Contrast Test to measure visual performance in USAF personnel after PRK.

PubMed

Dennis, Richard J; Beer, Jeremy M A; Baldwin, J Bruce; Ivan, Douglas J; Lorusso, Frank J; Thompson, William T

2004-07-01

Photorefractive keratectomy (PRK) may be an alternative to spectacle and contact lens wear for United States Air Force (USAF) aircrew and may offer some distinct advantages in operational situations. However, any residual corneal haze or scar formation from PRK could exacerbate the disabling effects of a bright glare source on a complex visual task. The USAF recently completed a longitudinal clinical evaluation of the long-term effects of PRK on visual performance, including the experiment described herein. After baseline data were collected, 20 nonflying active duty USAF personnel underwent PRK. Visual performance was then measured at 6, 12, and 24 months after PRK. Visual acuity (VA) and contrast sensitivity (CS) data were collected by using the Freiburg Acuity and Contrast Test (FrACT), with the subject viewing half of the runs through a polycarbonate windscreen. Experimental runs were completed under 3 glare conditions: no glare source and with either a broadband or a green laser (532-nm) glare annulus (luminance approximately 6090 cd/m) surrounding the Landolt C stimulus. Systematic effects of PRK on VA relative to baseline were not identified. However, VA was almost 2 full Snellen lines worse with the laser glare source in place versus the broadband glare source. A significant drop-off was observed in CS performance after PRK under conditions of no glare and broadband glare; this was the case both with and without the windscreen. As with VA, laser glare disrupted CS performance significantly and more than broadband glare did. PRK does not appear to have affected VA, but the changes in CS might represent a true decline in visual performance. The greater disruptive effects from laser versus broadband glare may be a result of increased masking from coherent spatial noise (speckle) surrounding the laser stimulus.

Identification and transcript profiles of citrus growth-regulating factor genes involved in the regulation of leaf and fruit development.

PubMed

Liu, Xiao; Guo, Ling-Xia; Jin, Long-Fei; Liu, Yong-Zhong; Liu, Tao; Fan, Yu-Hua; Peng, Shu-Ang

2016-10-01

Growth-regulating factor (GRF) is an important protein in GA-mediated response, with key roles in plant growth and development. However, it is not known whether or how the GRF proteins in citrus to regulate organ size. In this study, nine citrus GRF genes (CsGRF1-9) were validated from the 'Anliu' sweet orange (AL, Citrus sinensis cv. Anliu) by PCR amplification. They all contain two conserved motifs (QLQ and WRC) and have 3-4 exons. The transcript levels of genes were detected by qRT-PCR. Transcript analysis showed that (1) CsGRF 1, 2, 5, 6, 7, and 9 expressed predominantly in young leaf, CsGRF 3 and 4 expressed predominantly in fruit immature juice sacs and CsGRF 8 expressed predominantly in root; (2) all citrus GRF genes had significantly higher expression in young leaves than mature leaf; (3) in juice sacs, the transcript levels of CsGRF1, 4, 5, 6, and 8 increased significantly while the transcript levels of CsGRF2, 3, 7, and 9 had no significant change from 80 DAF to 100 DAF. Besides, GA3 treatment did not affect the transcript levels of CsGRF5 and CsGRF6 but significantly increased the transcript levels of the other seven CsGRF genes in young leaves. These results suggested that all CsGRF genes involve in the leaf development, CsGRF1, 4, 5, 6, and 8 act developmentally whilst CsGRF2, 3, 7, and 9 play fundamental roles in fruit cell enlargement, which may be through GA pathway or GA-independent pathway.

Pharmacological and gene regulation properties point to the SlHAK5 K+ transporter as a system for high-affinity Cs+ uptake in tomato plants.

PubMed

Ródenas, Reyes; Nieves-Cordones, Manuel; Rivero, Rosa M; Martinez, Vicente; Rubio, Francisco

2018-04-01

Potassium (K + ) and cesium (Cs + ) are chemically similar but while K + is an essential nutrient, Cs + can be toxic for living organisms, plants included. Two different situations could lead to problems derived from the presence of Cs + in agricultural systems: (1) presence of Cs + at high concentrations that could produce toxic effects on plants, (2) presence of micromolar concentrations of radiocesium, which can be accumulated in the plant and affect animal and human health through the food chain. While K + uptake has been well described in tomato plants, information on molecular mechanisms involved in Cs + accumulation in this species is absent. Here, we show that in tomato plants, high concentrations of Cs + produce deficiency of K + but do not induce high-affinity K + uptake or the gene encoding the high-affinity K + transporter SlHAK5. At these concentrations, Cs + uptake takes place through a Ca 2+ -sensitive pathway, probably a non-selective cation channel. At micromolar concentrations, Cs + is accumulated by a high-affinity uptake system upregulated in K + -starved plants. This high-affinity Cs + uptake shares features with high-affinity K + uptake. It is sensitive to NH 4 + and insensitive to Ba 2+ and Ca 2+ and its presence parallels the pattern of SlHAK5 expression. Moreover, blockers of reactive oxygen species and ethylene action repress SlHAK5 and negatively regulate both high-affinity K + and Cs + uptake. Thus, we propose that SlHAK5 contributes to Cs + uptake from micromolar concentrations in tomato plants and can constitute a pathway for radiocesium transfer from contaminated areas to the food chain. © 2017 Scandinavian Plant Physiology Society.

Serum metabonomics study of the hepatoprotective effect of Corydalis saxicola Bunting on carbon tetrachloride-induced acute hepatotoxicity in rats by (1)H NMR analysis.

PubMed

Liang, Yong-Hong; Tang, Chao-Ling; Lu, Shi-Yin; Cheng, Bang; Wu, Fang; Chen, Zhao-Ni; Song, Fangming; Ruan, Jun-Xiang; Zhang, Hong-Ye; Song, Hui; Zheng, Hua; Su, Zhi-Heng

2016-09-10

Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the exact hepatoprotective mechanism of CS was still looking forward to further elucidation by far. In present work, metabonomic study of biochemical changes in the serum of carbon tetrachloride (CCl4)-induced acute liver injury rats after CS treatment were performed using proton nuclear magnetic resonance ((1)H-NMR) analysis. Metabolic profiling by means of principal components analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation caused by CCl4 was reduced by CS treatment. A total of 9 metabolites including isoleucine (1), lactate (2), alanine (3), glutamine (4), acetone (5), succinate (6), phosphocholine (7), d-glucose (8) and glycerol (9) were considered as potential biomarkers involved in the development of CCl4-induced acute liver injury. According to pathway analysis by metabolites identified and correlation network construction by Pearson's correlation coefficency matrix, alanine, aspartate and glutamate metabolism and glycerolipid metabolism were recognized as the most influenced metabolic pathways associated with CCl4 injury. As a result, notably, deviations of metabolites 1, 3, 4, 7 and 9 in the process of CCl4-induced acute liver injury were improved by CS treatment, which suggested that CS mediated synergistically abnormalities of the metabolic pathways, composed of alanine, aspartate and glutamate metabolism and glycerolipid metabolism. In this study, it was the first report to investigate the hepatoprotective effect of the CS based on metabonomics strategy, which may be a potentially powerful tool to interpret the action mechanism of traditional Chinese folk medicines. Copyright © 2016 Elsevier B.V. All rights reserved.

Insight into Catechins Metabolic Pathways of Camellia sinensis Based on Genome and Transcriptome Analysis.

PubMed

Wang, Wenzhao; Zhou, Yihui; Wu, Yingling; Dai, Xinlong; Liu, Yajun; Qian, Yumei; Li, Mingzhuo; Jiang, Xiaolan; Wang, Yunsheng; Gao, Liping; Xia, Tao

2018-04-25

Tea is an important economic crop with a 3.02 Gb genome. It accumulates various bioactive compounds, especially catechins, which are closely associated with tea flavor and quality. Catechins are biosynthesized through the phenylpropanoid and flavonoid pathways, with 12 structural genes being involved in their synthesis. However, we found that in Camellia sinensis the understanding of the basic profile of catechins biosynthesis is still unclear. The gene structure, locus, transcript number, transcriptional variation, and function of multigene families have not yet been clarified. Our previous studies demonstrated that the accumulation of flavonoids in tea is species, tissue, and induction specific, which indicates that gene coexpression patterns may be involved in tea catechins and flavonoids biosynthesis. In this paper, we screened candidate genes of multigene families involved in the phenylpropanoid and flavonoid pathways based on an analysis of genome and transcriptome sequence data. The authenticity of candidate genes was verified by PCR cloning, and their function was validated by reverse genetic methods. In the present study, 36 genes from 12 gene families were identified and were accessed in the NCBI database. During this process, some intron retention events of the CsCHI and CsDFR genes were found. Furthermore, the transcriptome sequencing of various tea tissues and subcellular location assays revealed coexpression and colocalization patterns. The correlation analysis showed that CsCHIc, CsF3'H, and CsANRb expression levels are associated significantly with the concentration of soluble PA as well as the expression levels of CsPALc and CsPALf with the concentration of insoluble PA. This work provides insights into catechins metabolism in tea and provides a foundation for future studies.

Tetracycline Selective Pressure and Homologous Recombination Shape the Evolution of Chlamydia suis: A Recently Identified Zoonotic Pathogen.

PubMed

Joseph, Sandeep J; Marti, Hanna; Didelot, Xavier; Read, Timothy D; Dean, Deborah

2016-09-02

Species closely related to the human pathogen Chlamydia trachomatis (Ct) have recently been found to cause zoonotic infections, posing a public health threat especially in the case of tetracycline resistant Chlamydia suis (Cs) strains. These strains acquired a tet(C)-containing cassette via horizontal gene transfer (HGT). Genomes of 11 Cs strains from various tissues were sequenced to reconstruct evolutionary pathway(s) for tet(C) HGT. Cs had the highest recombination rate of Chlamydia species studied to date. Admixture occurred among Cs strains and with Chlamydia muridarum but not with Ct Although in vitro tet(C) cassette exchange with Ct has been documented, in vivo evidence may require examining human samples from Ct and Cs co-infected sites. Molecular-clock dating indicated that ancestral clades of resistant Cs strains predated the 1947 discovery of tetracycline, which was subsequently used in animal feed. The cassette likely spread throughout Cs strains by homologous recombination after acquisition from an external source, and our analysis suggests Betaproteobacteria as the origin. Selective pressure from tetracycline may be responsible for recent bottlenecks in Cs populations. Since tetracycline is an important antibiotic for treating Ct, zoonotic infections at mutual sites of infection indicate the possibility for cassette transfer and major public health repercussions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Comparison of contrast sensitivity in β-thalassemia patients treated by deferoxamine or deferasirox.

PubMed

Ghazanfari, Azam; Jafarzadehpour, Ebrahim; Heydarian, Samira; Nowroozpoor Dailami, Kiumars; Karami, Hosein

2018-03-10

To compare contrast sensitivity (CS) in multi-transfused β-thalassemia patients who received deferoxamine with those who received Osveral. In this cross sectional study a total of 60 β-thalassemia patients (30 used deferoxamine and 30 used deferasirox) were regarded as case group and 30 age and sex matched healthy subjects were selected as control group. All subjects had a set of examinations including refraction, visual acuity, Biomicroscopy, ophthalmoscopy and CS. Contrast threshold was assessed with the use of Freiberg visual acuity and contrast test under the mesopic light condition for three frequencies; 1, 5, 15cpd. All data analysis was performed using SPSS, version 17. In visual acuity tests, thalassemic patients did not have any problem. Contrast threshold was higher in thalassemic patients who infuse deferoxamine (1.87±0.63, 1.46±0.81, and 2.96±1.68 in 1, 5, and 15cpd, respectively) than that of those who intake deferasirox (1.74±0.80 (P=0.743), 0.99±0.74 (P=0.047), and 2.42±1.36 (P=0.321) for 1, 5, and 15cpd, respectively), and also than healthy patients (1.33±0.58 (P=0.009), 0.95±0.68 (P=0.022), and 2.24±1.23 (P=0.135) for 1, 5, and 15cpd, respectively). Comparing those who used deferasirox with healthy subjects, contrast threshold was higher in deferasirox group at all special frequencies (P>0.05). No significant relationship was observed between CS values and duration of transfusion, serum ferritin concentration and dose of chelation therapy (P>0.05). CS tests can detect visual disturbance in thalassemic patients before the impairment of visual acuity. It is suggested that CS tests be included in their regular eye examination. Copyright © 2018 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Contrast sensitivity to spatial gratings in moderate and dim light conditions in patients with diabetes in the absence of diabetic retinopathy

PubMed Central

Safi, Sare; Rahimi, Anoushiravan; Raeesi, Afsaneh; Safi, Hamid; Aghazadeh Amiri, Mohammad; Malek, Mojtaba; Yaseri, Mehdi; Haeri, Mohammad; Middleton, Frank A; Solessio, Eduardo; Ahmadieh, Hamid

2017-01-01

Objective To evaluate the ability of contrast sensitivity (CS) to discriminate loss of visual function in diabetic subjects with no clinical signs of retinopathy relative to that of normal subjects. Research design and methods In this prospective cross-sectional study, we measured CS in 46 diabetic subjects with a mean age of 48±6 years, a best-corrected visual acuity of 20/20 and no signs of diabetic retinopathy. The CS in these subjects was compared with CS measurements in 46 normal control subjects at four spatial frequencies (3, 6, 12, 18 cycles per degree) under moderate (500 lux) and dim (less than 2 lux) background light conditions. Results CS was approximately 0.16 log units lower in patients with diabetes relative to controls both in moderate and in dim background light conditions. Logistic regression classification and receiver operating characteristic curve analysis indicated that CS analysis using two light conditions was more accurate (0.78) overall compared with CS analysis using only a single illumination condition (accuracy values were 0.67 and 0.70 in moderate and dim light conditions, respectively). Conclusions Our results showed that patients with diabetes without clinical signs of retinopathy exhibit a uniform loss in CS at all spatial frequencies tested. Measuring the loss in CS at two spatial frequencies (3 and 6 cycles per degree) and two light conditions (moderate and dim) is sufficiently robust to classify diabetic subjects with no retinopathy versus control subjects. PMID:28878937

Functional FRIGIDA allele enhances drought tolerance by regulating the P5CS1 pathway in Arabidopsis thaliana.

PubMed

Chen, Qian; Zheng, Yan; Luo, Landi; Yang, Yongping; Hu, Xiangyang; Kong, Xiangxiang

2018-01-01

Flowering at the right time is important for the reproductive success of plants and their response to environmental stress. In Arabidopsis, a major determinant of natural variation in flowering time is FRIGIDA (FRI). In the present study, we show that overexpression of the functional FRIGIDA gene in wild-type Col background (ColFRI) positively enhances the drought tolerance by activating P5CS1 expression and promoting proline accumulation during water stress. Furthermore, no significant changes in FRI gene and protein expression levels were observed with drought treatment, whereas P5CS1 protein expression significantly increased. In contrast, vernalization treatment efficiently reduced P5CS1 expression levels and resulted in a decrease in drought tolerance in the ColFRI plants. The flc mutants with a functional FRI background also relieved FRI-mediated activation of P5CS1 during drought tolerance. Taken together, our findings reveal the novel function of FRI in enhancing drought resistance through its downstream P5CS1 pathway during water-deficit stress, which is dependent on its target, the FLC gene. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of visual status of Iranian military and commercial drivers.

PubMed

Ghasemi, Mohammad; Hoseini Yazdi, Seyed Hosein; Heravian, Javad; Jafarzadehpur, Ebrahim; Rezaee, Maryam

2015-04-01

There is no legal requirement for Iranian military truck drivers to undergo regular visual checkups as compared to commercial truck drivers. This study aimed to evaluate the impact of drivers' visual checkups by comparing the visual function of Iranian military and commercial truck drivers. In this comparative cross-sectional study, two hundred military and 200 commercial truck drivers were recruited and their Visual Acuity (VA), Visual Field (VF), color vision and Contrast Sensitivity (CS) were assessed and compared using the Snellen chart, confrontation screening method, D15 test and Pelli-Robson letter chart, respectively. A questionnaire regarding driving exposure and history of motor-vehicle crashes (MVCs) was also filled by drivers. Results were analyzed using an independent samples t-test, one-way ANOVA (assessing difference in number of MVCs across different age groups), chi-square test and Pearson correlation at statistical significance level of P < 0.05. Mean age was 41.6 ± 9.2 for the military truck drivers and 43.4 ± 10.9 for commercial truck drivers (P > 0.05). No significant difference between military and commercial drivers was found in terms of driving experience, number of MVCs, binocular VA, frequency of color vision defects and CS scores. In contrast, the last ocular examination was significantly earlier in military drivers than commercial drivers (P < 0.001). In addition, 4% of military drivers did not meet the national standards to drive as opposed to 2% of commercial drivers. There was a significant but weak correlation between binocular VA and age (r = 0.175, P < 0.001). However, CS showed a significantly moderate correlation with age (r = -0.488, P < 0.001). The absence of legal requirement for regular eye examination in military drivers caused the incompetent drivers to be missed in contrast to commercial drivers. The need for scientific revision of VA standard for Iranian drivers is also discussed. The CS measurement in visual checkups of older drivers deserves to be investigated more thoroughly.

Retinal vessel caliber among people with acquired immunodeficiency syndrome: relationships with visual function.

PubMed

Kalyani, Partho S; Fawzi, Amani A; Gangaputra, Sapna; van Natta, Mark L; Hubbard, Larry D; Danis, Ronald P; Thorne, Jennifer E; Holland, Gary N

2012-03-01

To evaluate relationships between retinal vessel caliber and tests of visual function among people with AIDS. Longitudinal, observational cohort study. We evaluated data for participants without ocular opportunistic infections at initial examination (baseline) in the Longitudinal Studies of the Ocular Complications of AIDS (1998-2008). Visual function was evaluated with best-corrected visual acuity, Goldmann perimetry, automated perimetry (Humphrey Field Analyzer), and contrast sensitivity (CS) testing. Semi-automated grading of fundus photographs (1 eye/participant) determined central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) at baseline. Multiple linear regression models, using forward selection, sought independent relationships between indices and visual function variables. Included were 1250 participants. Smaller AVR was associated with reduced visual field by Goldmann perimetry (P = .003) and worse mean deviation (P = .02) on automated perimetry and possibly with worse pattern standard deviation (PSD) on automated perimetry (P = .06). There was a weak association between smaller AVR and worse CS (P = .07). Relationships were independent of antiretroviral therapy and level of immunodeficiency (CD4+ T lymphocyte count, human immunodeficiency virus [HIV] RNA blood level). On longitudinal analysis, retinal vascular indices at baseline did not predict changes in visual function. Variation in retinal vascular indices is associated with abnormal visual function in people with AIDS, manifested by visual field loss and possibly by reduced CS. Relationships are consistent with the hypothesis that HIV-related retinal vasculopathy is a contributing factor to vision dysfunction among HIV-infected individuals. Longitudinal studies are needed to determine whether changes in indices predict change in visual function. Copyright © 2012 Elsevier Inc. All rights reserved.

Wavefront-Guided Versus Wavefront-Optimized Photorefractive Keratectomy: Visual and Military Task Performance.

PubMed

Ryan, Denise S; Sia, Rose K; Stutzman, Richard D; Pasternak, Joseph F; Howard, Robin S; Howell, Christopher L; Maurer, Tana; Torres, Mark F; Bower, Kraig S

2017-01-01

To compare visual performance, marksmanship performance, and threshold target identification following wavefront-guided (WFG) versus wavefront-optimized (WFO) photorefractive keratectomy (PRK). In this prospective, randomized clinical trial, active duty U.S. military Soldiers, age 21 or over, electing to undergo PRK were randomized to undergo WFG (n = 27) or WFO (n = 27) PRK for myopia or myopic astigmatism. Binocular visual performance was assessed preoperatively and 1, 3, and 6 months postoperatively: Super Vision Test high contrast, Super Vision Test contrast sensitivity (CS), and 25% contrast acuity with night vision goggle filter. CS function was generated testing at five spatial frequencies. Marksmanship performance in low light conditions was evaluated in a firing tunnel. Target detection and identification performance was tested for probability of identification of varying target sets and probability of detection of humans in cluttered environments. Visual performance, CS function, marksmanship, and threshold target identification demonstrated no statistically significant differences over time between the two treatments. Exploratory regression analysis of firing range tasks at 6 months showed no significant differences or correlations between procedures. Regression analysis of vehicle and handheld probability of identification showed a significant association with pretreatment performance. Both WFG and WFO PRK results translate to excellent and comparable visual and military performance. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Excitation Dynamics in Phycoerythrin 545: Modeling of Steady-State Spectra and Transient Absorption with Modified Redfield Theory

PubMed Central

Novoderezhkin, Vladimir I.; Doust, Alexander B.; Curutchet, Carles; Scholes, Gregory D.; van Grondelle, Rienk

2010-01-01

Abstract We model the spectra and excitation dynamics in the phycobiliprotein antenna complex PE545 isolated from the unicellular photosynthetic cryptophyte algae Rhodomonas CS24. The excitonic couplings between the eight bilins are calculated using the CIS/6-31G method. The site energies are extracted from a simultaneous fit of the absorption, circular dichroism, fluorescence, and excitation anisotropy spectra together with the transient absorption kinetics using the modified Redfield approach. Quantitative fit of the data enables us to assign the eight exciton components of the spectra and build up the energy transfer picture including pathways and timescales of energy relaxation, thus allowing a visualization of excitation dynamics within the complex. PMID:20643051

Functional plasticity in the interposito-thalamo-cortical pathway during conditioning. Role of the interstimulus interval.

PubMed

Pananceau, M; Rispal-Padel, L

2000-06-01

In classic conditioning, the interstimulus interval (ISI) between the conditioned (CS) and unconditioned (US) stimulus is a critical parameter. The aim of the present experiment was to assess whether, during conditioning, modification of the CS-US interval could reliably produce changes in the functional properties of the interposito-thalamo-cortical pathways (INTCps). Five cats were prepared for chronic stimulation and recording from several brain regions along this pathway in awake animals. The CS was a weak electric shock applied on the interposed nucleus of the cerebellum in sites that initially elicited forelimb flexion (i.e., alpha motor responses) in three cats, and equal proportions of flexor and extensor responses in two cats. The US was an electric shock applied on the skin that elicited forelimb flexions. The motor and neurobiological effects of synchronous CS-US were compared with pairings in which the CS was applied 100 ms before US. Simultaneous and sequential application of CS and US produced different behavioral outcomes and resulted in different neural processes in the interposito-thalamo-cortical pathways (INTCps). The simultaneous presentation of stimuli only produced a small increase in excitability spreading to all the body representational zones of the primary motor cortex and a weak increase in the amplitude of the alpha motor response. In contrast, the sequential application led to a profound modification of the interposed output to neurons in the forelimb representation of the motor cortex. These robust neuronal correlates of conditioning were accompanied by a large facilitation of the alpha motor response (alpha-MR). There were also changes in the direction of misdirected alpha responses and an emergence of functionally appropriate, long-latency withdrawal forelimb flexion. These data revealed that, during conditioning, plastic changes within the thalamocortical connections are selectively induced by sequential information from central and peripheral afferents. This sequence significantly contributed to neural processes that are responsible for the acquisition, expression, and extinction of anticipatory flexion responses.

Dichoptic training improves contrast sensitivity in adults with amblyopia.

PubMed

Li, Jinrong; Spiegel, Daniel P; Hess, Robert F; Chen, Zidong; Chan, Lily Y L; Deng, Daming; Yu, Minbin; Thompson, Benjamin

2015-09-01

Dichoptic training is designed to promote binocular vision in patients with amblyopia. Initial studies have found that the training effects transfer to both binocular (stereopsis) and monocular (recognition acuity) visual functions. The aim of this study was to assess whether dichoptic training effects also transfer to contrast sensitivity (CS) in adults with amblyopia. We analyzed CS data from 30 adults who had taken part in one of two previous dichoptic training studies and assessed whether the changes in CS exceeded the 95% confidence intervals for change based on test-retest data from a separate group of observers with amblyopia. CS was measured using Gabor patches (0.5, 3 and 10cpd) before and after 10days of dichoptic training. Training was delivered using a dichoptic video game viewed through video goggles (n=15) or on an iPod touch equipped with a lenticular overlay screen (n=15). In the iPod touch study, training was combined with anodal transcranial direct current stimulation of the visual cortex. We found that dichoptic training significantly improved CS across all spatial frequencies tested for both groups. These results suggest that dichoptic training modifies the sensitivity of the neural systems that underpin monocular CS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sparing of the Dystrophin-Deficient Cranial Sartorius Muscle Is Associated with Classical and Novel Hypertrophy Pathways in GRMD Dogs

PubMed Central

Nghiem, Peter P.; Hoffman, Eric P.; Mittal, Priya; Brown, Kristy J.; Schatzberg, Scott J.; Ghimbovschi, Svetlana; Wang, Zuyi; Kornegay, Joe N.

2014-01-01

Both Duchenne and golden retriever muscular dystrophy (GRMD) are caused by dystrophin deficiency. The Duchenne muscular dystrophy sartorius muscle and orthologous GRMD cranial sartorius (CS) are relatively spared/hypertrophied. We completed hierarchical clustering studies to define molecular mechanisms contributing to this differential involvement and their role in the GRMD phenotype. GRMD dogs with larger CS muscles had more severe deficits, suggesting that selective hypertrophy could be detrimental. Serial biopsies from the hypertrophied CS and other atrophied muscles were studied in a subset of these dogs. Myostatin showed an age-dependent decrease and an inverse correlation with the degree of GRMD CS hypertrophy. Regulators of myostatin at the protein (AKT1) and miRNA (miR-539 and miR-208b targeting myostatin mRNA) levels were altered in GRMD CS, consistent with down-regulation of myostatin signaling, CS hypertrophy, and functional rescue of this muscle. mRNA and proteomic profiling was used to identify additional candidate genes associated with CS hypertrophy. The top-ranked network included α-dystroglycan and like-acetylglucosaminyltransferase. Proteomics demonstrated increases in myotrophin and spectrin that could promote hypertrophy and cytoskeletal stability, respectively. Our results suggest that multiple pathways, including decreased myostatin and up-regulated miRNAs, α-dystroglycan/like-acetylglucosaminyltransferase, spectrin, and myotrophin, contribute to hypertrophy and functional sparing of the CS. These data also underscore the muscle-specific responses to dystrophin deficiency and the potential deleterious effects of differential muscle involvement. PMID:24160322

Myopic astigmatism correction: comparison of a Toric Implantable Collamer Lens and a bioptics technique by an adaptive optics visual simulator.

PubMed

Pérez-Vives, Cari; Domínguez-Vicent, Alberto; Madrid-Costa, David; Ferrer-Blasco, Teresa; Montés-Micó, Robert

2013-03-01

To compare the optical and visual quality of a simulated Toric Implantable Collamer Lens (TICL) and a bioptics technique to treat high myopic astigmatism. An adaptive optics visual simulator was used to simulate the vision after TICL implantation and a bioptics procedure from the wavefront aberration pattern for moderate and high-myopic astigmatism. Visual acuity (VA) at different contrasts and contrast sensitivity (CS) at 10, 20 and 25 cycles degree(-1) were measured for 3 and 5-mm pupils. Modulation Transfer Function (MTF) and Point Spread Function (PSF) were calculated for a 5-mm pupil. At a 3-mm pupil we only found statistically significant differences in VA between the two simulated surgeries at low-contrast for moderate- and high-myopic astigmatism (p < 0.05). Statistically significant differences were found in CS at 3-mm pupil between both procedures at the highest spatial frequency for moderate-myopic astigmatism and at all frequencies for high-myopic astigmatism (p < 0.05). At a 5-mm pupil we found statistically significant differences in VA and CS between both simulated surgeries at all contrasts and frequencies evaluated for both groups (p < 0.05). In all cases VA and CS were better with the TICL than with the bioptics technique. MTFs for the bioptics technique were worse than those computed for the TICL. The TICL showed less spread out of the PSF than the bioptics procedure. Simulated TICL and bioptics procedures provided good optical and visual quality, although TICL implantation provided slightly better outcomes than the bioptics procedure, especially when the pupil diameter was increased. Ophthalmic & Physiological Optics © 2013 The College of Optometrists.

Levodopa-carbidopa with occlusion in older children with amblyopia.

PubMed

Bhartiya, Prashant; Sharma, Pradeep; Biswas, Nihar R; Tandon, Radhika; Khokhar, Sudarshan K

2002-12-01

To study the role of levodopa-carbidopa in supplementing occlusion therapy in older children with strabismic or anisometropic amblyopia. A clinical study was performed on 40 amblyopic children (19 strabismic and 21 anisometropic), 6 to 18 years old (mean age, 10.9 years). They received an average dose of 1.86 mg/kg/day (1.33-2.36 mg/kg/day) of levodopa and carbidopa (4:1 ratio) or a placebo in 3 divided doses over a 4-week period, combined with full-time occlusion. The occlusion was continued for the study duration of 3 months. Early Treatment Diabetic Retinopathy Study visual acuity charts and Cambridge low-contrast gratings for contrast sensitivity (CS) were used to assess visual functions. Tolerance and compliance with occlusion and capsule consumption were assessed. Visual acuity of the nonamblyopic eye did not deteriorate during the study in either group. CS decreased by 22 units in the levodopa group and increased in the placebo group by 53 units at the first month. The CS in the levodopa group recovered later by the third month of follow-up. Both the levodopa and the placebo groups showed significant improvement in visual function in the amblyopic eye (P <.001). Overall changes in logarithm of minimum angle of resolution values and CS in the amblyopic eyes were similar in both groups (P >.05). Strabismic and anisometropic amblyopes did not behave differently. Drug tolerance, occlusion compliance, and capsule ingestion compliance were similar between the groups, with no significant side effects. Clinically, levodopa supplementation does not offer any advantage over occlusion alone. Moreover, the risk of occlusion amblyopia could increase with the use of drugs like levodopa that might affect the plasticity of the visual cortex.

Large Vocabulary Audio-Visual Speech Recognition

DTIC Science & Technology

2002-06-12

www.is.cs.cmu.edu Email: waibel(a)cs.cmu~edu Inttractive Systenms Labs ttoctis Ssstms Labs Meeting Browser - -- Interpreting Human Communication "Why did...Speech Interacti Stams Labs t-cive Systms Focus of Attention Tracking Conclusion - Complete Model of Human Communication is Needed - Include all

A pharmacologically-based array to identify targets of cyclosporine A-induced toxicity in cultured renal proximal tubule cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarró, Eduard, E-mail: eduard.sarro@vhir.org; Renal Physiopathology, CIBBIM-Nanomedicine, Vall d'Hebron Research Institute; Jacobs-Cachá, Conxita, E-mail: conxita.jacobs@vhir.org

2012-01-15

Mechanisms of cyclosporine A (CsA)-induced nephrotoxicity were generally thought to be hemodynamic in origin; however, there is now accumulating evidence of a direct tubular effect. Although genomic and proteomic experiments by our group and others provided overall information on genes and proteins up- or down-regulated by CsA in proximal tubule cells (PTC), a comprehensive view of events occurring after CsA exposure remains to be described. For this purpose, we applied a pharmacologic approach based on the use of known activities of a large panel of potentially protective compounds and evaluated their efficacy in preventing CsA toxicity in cultured mouse PTC.more » Our results show that compounds that blocked protein synthesis and apoptosis, together with the CK2 inhibitor DMAT and the PI3K inhibitor apigenin, were the most efficient in preventing CsA toxicity. We also identified GSK3, MMPs and PKC pathways as potential targets to prevent CsA damage. Additionally, heparinase-I and MAPK inhibitors afforded partial but significant protection. Interestingly, antioxidants and calcium metabolism-related compounds were unable to ameliorate CsA-induced cytotoxicity. Subsequent experiments allowed us to clarify the hierarchical relationship of targeted pathways after CsA treatment, with ER stress identified as an early effector of CsA toxicity, which leads to ROS generation, phenotypical changes and cell death. In summary, this work presents a novel experimental approach to characterizing cellular responses to cytotoxics while pointing to new targets to prevent CsA-induced toxicity in proximal tubule cells. Highlights: ► We used a novel pharmacological approach to elucidate cyclosporine (CsA) toxicity. ► The ability of a broad range of compounds to prevent CsA toxicity was evaluated. ► CsA toxicity was monitored using LDH release assay and PARP cleavage. ► Protein synthesis, PI3K, GSK3, MMP, PKC and caspase inhibitors prevented CsA toxicity. ► We also identified ER stress as an early effector of CsA toxicity.« less

Bilateral Activity-Dependent Interactions in the Developing Corticospinal System

PubMed Central

Friel, Kathleen M.; Martin, John H.

2009-01-01

Activity-dependent competition between the corticospinal (CS) systems in each hemisphere drives postnatal development of motor skills and stable CS tract connections with contralateral spinal motor circuits. Unilateral restriction of motor cortex (M1) activity during an early postnatal critical period impairs contralateral visually guided movements later in development and in maturity. Silenced M1 develops aberrant connections with the contralateral spinal cord whereas the initially active M1, in the other hemisphere, develops bilateral connections. In this study, we determined whether the aberrant pattern of CS tract terminations and motor impairments produced by early postnatal M1 activity restriction could be abrogated by reducing activity-dependent synaptic competition from the initially active M1 later in development. We first inactivated M1 unilaterally between postnatal weeks 5–7. We next inactivated M1 on the other side from weeks 7–11 (alternate inactivation), to reduce the competitive advantage that this side may have over the initially inactivated side. Alternate inactivation redirected aberrant contralateral CS tract terminations from the initially silenced M1 to their normal spinal territories and reduced the density of aberrant ipsilateral terminations from the initially active side. Normal movement endpoint control during visually guided locomotion was fully restored. This reorganization of CS terminals reveals an unsuspected late plasticity after the critical period for establishing the pattern of CS terminations in the spinal cord. Our findings show that robust bilateral interactions between the developing CS systems on each side are important for achieving balance between contralateral and ipsilateral CS tract connections and visuomotor control. PMID:17928450

CS Riot Control Agent Exposure in US Army Mask Confidence Training: Association Between Exposure to O-Chlorobenzylidene Malononitrile (CS) and Urinary Metabolite 2-Chlorophippuric Acid

DTIC Science & Technology

2016-05-20

9 Figure 3. Major and Minor Metabolic Pathway of CS in the Body (37) .......................... 11 Figure 4. OSHA Versatile Sampler...the primary metabolite of CS in the body (8). This study will utilize Method ERB-2537 for quantification of CHA levels in exposed test subjects...intermediate that serves as a source of high energy in skeletal muscle and the brain (38). Creatine is produced in the body , can be consumed through foods

Identification, cloning and characterization of an ultrapetala transcription factor CsULT1 from Crocus: a novel regulator of apocarotenoid biosynthesis.

PubMed

Ashraf, Nasheeman; Jain, Deepti; Vishwakarma, Ram A

2015-02-01

Crocus sativus is a triploid sterile plant with long red stigmas which form commercial saffron. Saffron is the site for synthesis and accumulation of apocarotenoids like crocin, picrocrin and safranal which are responsible for its color, flavour and aroma making it world's most expensive spice. These compounds are formed by oxidative cleavage of zeaxanthin by carotenoid cleavage dioxygenases. Although the biosynthetic pathway of apocarotenoids is known to a considerable extent, the mechanism that regulates its tissue and developmental stage specific expression is not known. In the present work, we identified, cloned and characterized ultrapetala transcription factor called CsULT1 from Crocus. The gene contains an 80 amino acid long conserved SAND domain. The CsULT1 transcript was more abundant in stigma and showed increase in expression from pre anthesis stage till anthesis and decreased in post anthesis stage which corroborated with the accumulation pattern of crocin indicating its possible role in regulation of apocarotenoid biosynthesis. CsULT1 was found to be transcriptionally active and localized in nucleus. Its expression is induced in response to phytohormones like auxin, methyljasmonate and salicylic acid. Overexpression of CsULT1 in Crocus calli resulted in enhanced expression of key pathway genes like phytoene synthase (PSY), phytoene desaturase (PDS), beta carotene hydroxylase (BCH) and carotenoid cleavage dioxygenases (CCDs) indicating its role in regulation of apocarotenoid biosynthesis. This work presents first report on isolation and characterization of ultrapetala gene from Crocus. Our results suggest that CsULT1 is a novel regulator of Crocus apocarotenoid biosynthesis. We show for the first time involvement of plant SAND domain proteins in regulating secondary metabolic pathways.

CsGOGAT Is Important in Dynamic Changes of Theanine Content in Postharvest Tea Plant Leaves under Different Temperature and Shading Spreadings.

PubMed

Liu, Zhi-Wei; Li, Hui; Wang, Wen-Li; Wu, Zhi-Jun; Cui, Xin; Zhuang, Jing

2017-11-08

We analyzed the changes of theanine content in postharvest tea leaves under high temperature (38 °C), low temperature (4 °C), and shading spreadings by using ultrahigh-performance liquid chromatography. The differentially expressed proteins (DEPs), CsFd-GOGAT and CsNADH-GOGAT, which are involved in theanine biosynthesis pathway, were identified from the corresponding proteome data. The protein-protein interactions of CsFd-GOGAT and CsNADH-GOGAT, CsTS1, or CsNiR were verified by yeast two-hybrid technology. The expression profiles of 17 genes in theanine metabolism, including CsFd-GOGAT and CsNADH-GOGAT, were analyzed by quantitative real-time polymerase chain reaction. The correlations between the dynamic changes of theanine content and expression profiles of related genes and DEPs were analyzed. This study preliminarily proved the importance of CsGOGAT in dynamic changes of theanine content in postharvest tea leaves during spreading.

Silymarin attenuates cigarette smoke extract-induced inflammation via simultaneous inhibition of autophagy and ERK/p38 MAPK pathway in human bronchial epithelial cells.

PubMed

Li, Diandian; Hu, Jun; Wang, Tao; Zhang, Xue; Liu, Lian; Wang, Hao; Wu, Yanqiu; Xu, Dan; Wen, Fuqiang

2016-11-22

Cigarette smoke (CS) is a major risk of chronic obstructive pulmonary disease (COPD), contributing to airway inflammation. Our previous study revealed that silymarin had an anti-inflammatory effect in CS-exposed mice. In this study, we attempt to further elucidate the molecular mechanisms of silymarin in CS extract (CSE)-induced inflammation using human bronchial epithelial cells. Silymarin significantly suppressed autophagy activation and the activity of ERK/p38 mitogen-activated protein kinase (MAPK) pathway in Beas-2B cells. We also observed that inhibiting the activity of ERK with specific inhibitor U0126 led to reduced autophagic level, while knockdown of autophagic gene Beclin-1 and Atg5 decreased the levels of ERK and p38 phosphorylation. Moreover, silymarin attenuated CSE-induced upregulation of inflammatory cytokines TNF-α, IL-6 and IL-8 which could also be dampened by ERK/p38 MAPK inhibitors and siRNAs for Beclin-1 and Atg5. Finally, we validated decreased levels of both autophagy and inflammatory cytokines (TNF-α and KC) in CS-exposed mice after silymarin treatment. The present research has demonstrated that CSE-induced autophagy in bronchial epithelia, in synergism with ERK MAPK pathway, may initiate and exaggerate airway inflammation. Silymarin could attenuate inflammatory responses through intervening in the crosstalk between autophagy and ERK MAPK pathway, and might be an ideal agent treating inflammatory pulmonary diseases.

Biosynthesis and function of chondroitin sulfate.

PubMed

Mikami, Tadahisa; Kitagawa, Hiroshi

2013-10-01

Chondroitin sulfate proteoglycans (CSPGs) are principal pericellular and extracellular components that form regulatory milieu involving numerous biological and pathophysiological phenomena. Diverse functions of CSPGs can be mainly attributed to structural variability of their polysaccharide moieties, chondroitin sulfate glycosaminoglycans (CS-GAG). Comprehensive understanding of the regulatory mechanisms for CS biosynthesis and its catabolic processes is required in order to understand those functions. Here, we focus on recent advances in the study of enzymatic regulatory pathways for CS biosynthesis including successive modification/degradation, distinct CS functions, and disease phenotypes that have been revealed by perturbation of the respective enzymes in vitro and in vivo. Fine-tuned machineries for CS production/degradation are crucial for the functional expression of CS chains in developmental and pathophysiological processes. Control of enzymes responsible for CS biosynthesis/catabolism is a potential target for therapeutic intervention for the CS-associated disorders. Copyright © 2013 Elsevier B.V. All rights reserved.

Screening for germline phosphatase and tensin homolog-mutations in suspected Cowden syndrome and Cowden syndrome-like families among uterine cancer patients

PubMed Central

TZORTZATOS, GERASIMOS; ARAVIDIS, CHRISTOS; LINDBLOM, ANNIKA; MINTS, MIRIAM; THAM, EMMA

2015-01-01

Cowden syndrome (CS) is an autosomal dominant disorder characterized by multiple hamartomas in the breast, thyroid and endometrium, with a prevalence of 1 per 250,000. Females with CS have a 21–28% lifetime risk of developing uterine cancer. Germline mutations in the phosphatase and tensin homolog (PTEN) gene, a tumor suppressor gene, are responsible for 30–80% of CS cases. PTEN is a nine-exon gene, located on chromosome 10q23.3, which encodes the 403 amino acid PTEN protein. It negatively regulates the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway, affecting various cellular processes and signaling pathways. The present study examined whether PTEN mutations are present in CS-like families with uterine cancer (UC). UC patients underwent surgery at Karolinska University Hospital, Stockholm, Sweden (2008–2012). Pedigrees were analyzed and 54 unrelated CS-like families were identified. CS-like families were defined as having at least one occurrence of uterine cancer and one of breast cancer, as well as at least one additional Cowden-associated tumor (uterine, breast, thyroid, colon or kidney cancer) in the same individual or in first-degree relatives. Genomic DNA was amplified using polymerase chain reaction, and DNA sequencing analysis of all nine exons of the PTEN gene was conducted. No germline PTEN mutations or polymorphisms were identified. Germline PTEN mutations are rare in CS-like families with uterine cancer, therefore, genetic screening must be restricted to patients that meet the strict National Comprehensive Cancer Network criteria. Gynecologists must be aware of the CS criteria and identify potential cases of CS in females where uterine cancer is the sentinel cancer. PMID:25789042

Enhancing second-order conditioning with lesions of the basolateral amygdala.

PubMed

Holland, Peter C

2016-04-01

Because the occurrence of primary reinforcers in natural environments is relatively rare, conditioned reinforcement plays an important role in many accounts of behavior, including pathological behaviors such as the abuse of alcohol or drugs. As a result of pairing with natural or drug reinforcers, initially neutral cues acquire the ability to serve as reinforcers for subsequent learning. Accepting a major role for conditioned reinforcement in everyday learning is complicated by the often-evanescent nature of this phenomenon in the laboratory, especially when primary reinforcers are entirely absent from the test situation. Here, I found that under certain conditions, the impact of conditioned reinforcement could be extended by lesions of the basolateral amygdala (BLA). Rats received first-order Pavlovian conditioning pairings of 1 visual conditioned stimulus (CS) with food prior to receiving excitotoxic or sham lesions of the BLA, and first-order pairings of another visual CS with food after that surgery. Finally, each rat received second-order pairings of a different auditory cue with each visual first-order CS. As in prior studies, relative to sham-lesioned control rats, lesioned rats were impaired in their acquisition of second-order conditioning to the auditory cue paired with the first-order CS that was trained after surgery. However, lesioned rats showed enhanced and prolonged second-order conditioning to the auditory cue paired with the first-order CS that was trained before amygdala damage was made. Implications for an enhanced role for conditioned reinforcement by drug-related cues after drug-induced alterations in neural plasticity are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Die Fledermaus: Regarding Optokinetic Contrast Sensitivity and Light-Adaptation, Chicks Are Mice with Wings

PubMed Central

Shi, Qing; Stell, William K.

2013-01-01

Background Through adaptation, animals can function visually under an extremely broad range of light intensities. Light adaptation starts in the retina, through shifts in photoreceptor sensitivity and kinetics plus modulation of visual processing in retinal circuits. Although considerable research has been conducted on retinal adaptation in nocturnal species with rod-dominated retinas, such as the mouse, little is known about how cone-dominated avian retinas adapt to changes in mean light intensity. Methodology/Principal Findings We used the optokinetic response to characterize contrast sensitivity (CS) in the chick retina as a function of spatial frequency and temporal frequency at different mean light intensities. We found that: 1) daytime, cone-driven CS was tuned to spatial frequency; 2) nighttime, presumably rod-driven CS was tuned to temporal frequency and spatial frequency; 3) daytime, presumably cone-driven CS at threshold intensity was invariant with temporal and spatial frequency; and 4) daytime photopic CS was invariant with clock time. Conclusion/Significance Light- and dark-adaptational changes in CS were investigated comprehensively for the first time in the cone-dominated retina of an avian, diurnal species. The chick retina, like the mouse retina, adapts by using a “day/night” or “cone/rod” switch in tuning preference during changes in lighting conditions. The chick optokinetic response is an attractive model for noninvasive, behavioral studies of adaptation in retinal circuitry in health and disease. PMID:24098693

Sparing of the dystrophin-deficient cranial sartorius muscle is associated with classical and novel hypertrophy pathways in GRMD dogs.

PubMed

Nghiem, Peter P; Hoffman, Eric P; Mittal, Priya; Brown, Kristy J; Schatzberg, Scott J; Ghimbovschi, Svetlana; Wang, Zuyi; Kornegay, Joe N

2013-11-01

Both Duchenne and golden retriever muscular dystrophy (GRMD) are caused by dystrophin deficiency. The Duchenne muscular dystrophy sartorius muscle and orthologous GRMD cranial sartorius (CS) are relatively spared/hypertrophied. We completed hierarchical clustering studies to define molecular mechanisms contributing to this differential involvement and their role in the GRMD phenotype. GRMD dogs with larger CS muscles had more severe deficits, suggesting that selective hypertrophy could be detrimental. Serial biopsies from the hypertrophied CS and other atrophied muscles were studied in a subset of these dogs. Myostatin showed an age-dependent decrease and an inverse correlation with the degree of GRMD CS hypertrophy. Regulators of myostatin at the protein (AKT1) and miRNA (miR-539 and miR-208b targeting myostatin mRNA) levels were altered in GRMD CS, consistent with down-regulation of myostatin signaling, CS hypertrophy, and functional rescue of this muscle. mRNA and proteomic profiling was used to identify additional candidate genes associated with CS hypertrophy. The top-ranked network included α-dystroglycan and like-acetylglucosaminyltransferase. Proteomics demonstrated increases in myotrophin and spectrin that could promote hypertrophy and cytoskeletal stability, respectively. Our results suggest that multiple pathways, including decreased myostatin and up-regulated miRNAs, α-dystroglycan/like-acetylglucosaminyltransferase, spectrin, and myotrophin, contribute to hypertrophy and functional sparing of the CS. These data also underscore the muscle-specific responses to dystrophin deficiency and the potential deleterious effects of differential muscle involvement. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Comparison of Visual Status of Iranian Military and Commercial Drivers

PubMed Central

Ghasemi, Mohammad; Hoseini Yazdi, Seyed Hosein; Heravian, Javad; Jafarzadehpur, Ebrahim; Rezaee, Maryam

2015-01-01

Background: There is no legal requirement for Iranian military truck drivers to undergo regular visual checkups as compared to commercial truck drivers. Objectives: This study aimed to evaluate the impact of drivers’ visual checkups by comparing the visual function of Iranian military and commercial truck drivers. Patients and Methods: In this comparative cross-sectional study, two hundred military and 200 commercial truck drivers were recruited and their Visual Acuity (VA), Visual Field (VF), color vision and Contrast Sensitivity (CS) were assessed and compared using the Snellen chart, confrontation screening method, D15 test and Pelli-Robson letter chart, respectively. A questionnaire regarding driving exposure and history of motor-vehicle crashes (MVCs) was also filled by drivers. Results were analyzed using an independent samples t-test, one-way ANOVA (assessing difference in number of MVCs across different age groups), chi-square test and Pearson correlation at statistical significance level of P < 0.05. Results: Mean age was 41.6 ± 9.2 for the military truck drivers and 43.4 ± 10.9 for commercial truck drivers (P > 0.05). No significant difference between military and commercial drivers was found in terms of driving experience, number of MVCs, binocular VA, frequency of color vision defects and CS scores. In contrast, the last ocular examination was significantly earlier in military drivers than commercial drivers (P < 0.001). In addition, 4% of military drivers did not meet the national standards to drive as opposed to 2% of commercial drivers. There was a significant but weak correlation between binocular VA and age (r = 0.175, P < 0.001). However, CS showed a significantly moderate correlation with age (r = -0.488, P < 0.001). Conclusions: The absence of legal requirement for regular eye examination in military drivers caused the incompetent drivers to be missed in contrast to commercial drivers. The need for scientific revision of VA standard for Iranian drivers is also discussed. The CS measurement in visual checkups of older drivers deserves to be investigated more thoroughly. PMID:26023333

Role of ribonuclease L in viral pathogen-associated molecular pattern/influenza virus and cigarette smoke-induced inflammation and remodeling.

PubMed

Zhou, Yang; Kang, Min-Jong; Jha, Babal Kant; Silverman, Robert H; Lee, Chun Geun; Elias, Jack A

2013-09-01

Interactions between cigarette smoke (CS) exposure and viral infection play an important role(s) in the pathogenesis of chronic obstructive pulmonary disease and a variety of other disorders. A variety of lines of evidence suggest that this interaction induces exaggerated inflammatory, cytokine, and tissue remodeling responses. We hypothesized that the 2'-5' oligoadenylate synthetase (OAS)/RNase L system, an innate immune antiviral pathway, plays an important role in the pathogenesis of these exaggerated responses. To test this hypothesis, we characterize the activation of 2'-5' OAS in lungs from mice exposed to CS and viral pathogen-associated molecular patterns (PAMPs)/live virus, alone and in combination. We also evaluated the inflammatory and remodeling responses induced by CS and virus/viral PAMPs in lungs from RNase L null and wild-type mice. These studies demonstrate that CS and viral PAMPs/live virus interact in a synergistic manner to stimulate the production of select OAS moieties. They also demonstrate that RNase L plays a critical role in the pathogenesis of the exaggerated inflammatory, fibrotic, emphysematous, apoptotic, TGF-β1, and type I IFN responses induced by CS plus virus/viral PAMP in combination. These studies demonstrate that CS is an important regulator of antiviral innate immunity, highlight novel roles of RNase L in CS plus virus induced inflammation, tissue remodeling, apoptosis, and cytokine elaboration and highlight pathways that may be operative in chronic obstructive pulmonary disease and mechanistically related disorders.

Cesium-137 body burdens in Norwegian Lapps, 1965-1983.

PubMed

Westerlund, E A; Berthelsen, T; Berteig, L

1987-02-01

Results of measurements of the whole-body contents of 137Cs during the period 1965-1983 in Lapps from the Kautokeino area in Norway are reported with measurements of 137Cs in reindeer meat during the period 1966-1983. By using available data on 137Cs in precipitation for the period 1950-1980, transfer coefficients from 137Cs in precipitation to reindeer meat have been assessed. A correlation between the 137Cs content in reindeer meat and the 137Cs content in Lapp reindeer breeders has been established. The average whole-body committed dose equivalent, H50, to the reindeer breeders from internally deposited 137Cs from intakes up to year 2000 was assessed to 13 mSv with a peak value of 30 mSv. In comparison, the corresponding committed dose equivalent to the Norwegian population from internally deposited 137Cs has been estimated to be about 1 mSv. The higher intake of 137Cs by reindeer breeders is due to the lichen-reindeer-man exposure pathway.

The application of online transcranial random noise stimulation and perceptual learning in the improvement of visual functions in mild myopia.

PubMed

Camilleri, Rebecca; Pavan, Andrea; Campana, Gianluca

2016-08-01

It has recently been demonstrated how perceptual learning, that is an improvement in a sensory/perceptual task upon practice, can be boosted by concurrent high-frequency transcranial random noise stimulation (tRNS). It has also been shown that perceptual learning can generalize and produce an improvement of visual functions in participants with mild refractive defects. By using three different groups of participants (single-blind study), we tested the efficacy of a short training (8 sessions) using a single Gabor contrast-detection task with concurrent hf-tRNS in comparison with the same training with sham stimulation or hf-tRNS with no concurrent training, in improving visual acuity (VA) and contrast sensitivity (CS) of individuals with uncorrected mild myopia. A short training with a contrast detection task is able to improve VA and CS only if coupled with hf-tRNS, whereas no effect on VA and marginal effects on CS are seen with the sole administration of hf-tRNS. Our results support the idea that, by boosting the rate of perceptual learning via the modulation of neuronal plasticity, hf-tRNS can be successfully used to reduce the duration of the perceptual training and/or to increase its efficacy in producing perceptual learning and generalization to improved VA and CS in individuals with uncorrected mild myopia. Copyright © 2016 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salloum, Maher; Fabian, Nathan D.; Hensinger, David M.

Exascale computing promises quantities of data too large to efficiently store and transfer across networks in order to be able to analyze and visualize the results. We investigate compressed sensing (CS) as an in situ method to reduce the size of the data as it is being generated during a large-scale simulation. CS works by sampling the data on the computational cluster within an alternative function space such as wavelet bases and then reconstructing back to the original space on visualization platforms. While much work has gone into exploring CS on structured datasets, such as image data, we investigate itsmore » usefulness for point clouds such as unstructured mesh datasets often found in finite element simulations. We sample using a technique that exhibits low coherence with tree wavelets found to be suitable for point clouds. We reconstruct using the stagewise orthogonal matching pursuit algorithm that we improved to facilitate automated use in batch jobs. We analyze the achievable compression ratios and the quality and accuracy of reconstructed results at each compression ratio. In the considered case studies, we are able to achieve compression ratios up to two orders of magnitude with reasonable reconstruction accuracy and minimal visual deterioration in the data. Finally, our results suggest that, compared to other compression techniques, CS is attractive in cases where the compression overhead has to be minimized and where the reconstruction cost is not a significant concern.« less

A Unique Testing System for Audio Visual Foreign Language Laboratory.

ERIC Educational Resources Information Center

Stama, Spelios T.

1980-01-01

Described is the design of a low maintenance, foreign language laboratory at Ithaca College, New York, that provides visual and audio instruction, flexibility for testing, and greater student involvement in the lessons. (Author/CS)

Projection-specific visual feature encoding by layer 5 cortical subnetworks

PubMed Central

Lur, Gyorgy; Vinck, Martin A.; Tang, Lan; Cardin, Jessica A.; Higley, Michael J.

2016-01-01

Summary Primary neocortical sensory areas act as central hubs, distributing afferent information to numerous cortical and subcortical structures. However, it remains unclear whether each downstream target receives distinct versions of sensory information. We used in vivo calcium imaging combined with retrograde tracing to monitor visual response properties of three distinct subpopulations of projection neurons in primary visual cortex. While there is overlap across the groups, on average corticotectal (CT) cells exhibit lower contrast thresholds and broader tuning for orientation and spatial frequency in comparison to corticostriatal (CS) cells, while corticocortical (CC) cells have intermediate properties. Noise correlational analyses support the hypothesis that CT cells integrate information across diverse layer 5 populations, whereas CS and CC cells form more selectively interconnected groups. Overall, our findings demonstrate the existence of functional subnetworks within layer 5 that may differentially route visual information to behaviorally relevant downstream targets. PMID:26972011

7. Survivable low frequency communication system pathway, looking east ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. Survivable low frequency communication system pathway, looking east - Ellsworth Air Force Base, Delta Flight, Launch Control Facility, County Road CS23A, North of Exit 127, Interior, Jackson County, SD

Corticostriatal and corticotectal neurons in area 6 of the cat during fixation and eye movements.

PubMed

Weyand, T G; Gafka, A C

1998-01-01

We studied the visuomotor properties of 54 corticostriatal (CS) and 38 corticotectal (CT) neurons in a region of area 6 that largely corresponds to the cat's frontal eye fields in five cats trained to do simple oculomotor tasks. Overall, these cells were similar to the general population of area 6 neurons described in the previous paper (Weyand & Gafka, 1998), with very few showing pre-saccadic activity. Likewise, CS and CT cells were similar to each other, although only CS cells showed activity exclusively related to the delivery of the reward and CT cells were more likely to be active during saccades. Variability in visual response latencies and the observation that some cells showed initial visual suppression suggest CS and CT cells reflect the output of a variety of intracortical circuits. Despite similar response properties and overlapping laminar origin, CS and CT circuits appear largely independent. Among 32 cells that we could electrically activate (either synaptically or antidromically) from the superior colliculus, only two could also be activated from stimulating electrodes in the striatum. Similarly, 23 of 25 cells electrically activated from the striatum could not be activated from the superior colliculus. Although few of these efferent cells exhibited pre-motor activity, many exhibit properties that could contribute to gaze control.

Cross-sectional study assessing the addition of contrast sensitivity to visual acuity when testing for fitness to drive

PubMed Central

Spreng, Lucie; Favrat, Bernard; Borruat, François-Xavier; Vaucher, Paul

2018-01-01

Objectives The aim of this study is to quantify the importance of loss of contrast sensitivity (CS) and its relationship to loss of visual acuity (VA), driving restrictions and daytime, on-road driving evaluations in drivers aged 70+. Design A predictive cross-sectional study. Setting Volunteer participants to a drivers’ refresher course for adults aged 70+ delivered by the Swiss Automobile Club in western Switzerland from 2011 to 2013. Participants 162 drivers, male and female, aged 70 years or older. Clinical predictors We used a vision screener to estimate VA and the The Mars Letter Contrast Sensitivity Test to test CS. Outcomes We asked drivers to report whether they found five driving restrictions useful for their condition; restrict driving to known roads, avoid driving on highways, avoid driving in the dark, avoid driving in dense traffic and avoid driving in fog. All participants also underwent a standardised on-road evaluation carried out by a driving instructor. Results Moderate to severe loss of CS for at least one eye was frequent (21.0% (95% CI 15.0% to 28.1%)) and often isolated from a loss of VA (11/162 cases had a VA ≥0.8 decimal and a CS of ≤1.5 log(CS); 6.8% (95% CI 3.4% to 11.8%)). Drivers were more likely (R2=0.116, P=0.004) to report a belief that self-imposed driving restrictions would be useful if they had reduced CS in at least one eye. Daytime evaluation of driving performance seems limited in its ability to correctly identify difficulties related to CS loss (VA: R2=0.004, P=0.454; CS: R2=0.006, P=0.332). Conclusion CS loss is common for older drivers. Screening CS and referring for cataract surgery even in the absence of VA loss could help maintain mobility. Reduced CS and moderate reduction of VA were both poor predictors of daytime on-road driving performances in this research study. PMID:29374663

Visualization on triangle concept using Adobe Flash Professional SC6

NASA Astrophysics Data System (ADS)

Sagita, Laela; Ratih Kusumarini, Adha

2017-12-01

The purpose of this paper is to develop teaching aids using Adobe Flash Professional CS6 emphasize on Triangle concept. A new alternative way to deliver a basic concept in geometry with visualization is software Adobe Flash Professional CS 6. Research method is research and development with 5 phase of Ploom’s model, namely (1) preliminary, (2) design, (3) realization/ construction, (4) test, evaluation and revision, and 5) implementation. The results showed that teaching aids was valid, practice, and effective. Validity: expert judgement for material score is 3.95 and media expert judgement produce an average score of 3,2, both in the category are valid. Practically: the average of questionnaire response is 4,04 (good). Effectiveness: n-gain test value is 0,36 (medium). It concluded that developed of teaching aids using Adobe Flash CS6 on triangle can improve student achievement.

Does Central Vision Loss Impair Visual Search Performance of Adults More than Children?

PubMed

Satgunam, PremNandhini; Luo, Gang

2018-05-01

In general, young adults with normal vision show the best visual search performance when compared with children and older adults. Through our study, we show that this trend is not observed in individuals with vision impairment. An interaction effect of vision impairment with visual development and aging is observed. Performance in many visual tasks typically shows improvement with age until young adulthood and then declines with aging. Using a visual search task, this study investigated whether a similar age effect on performance is present in people with central vision loss. A total of 98 participants, 37 with normal sight (NS) and 61 with visual impairment (VI) searched for targets in 150 real-world digital images. Search performance was quantified by an integrated measure combining speed and accuracy. Participant ages ranged from 5 to 74 years, visual acuity from -0.14 (20/14.5) to 1.16 logMAR (20/290), and log contrast sensitivity (CS) from 0.48 to 2.0. Data analysis was performed with participants divided into three age groups: children (aged <14 years, n = 25), young adults (aged 14 to 45 years, n = 47), and older adults (aged >45 years, n = 26). Regression (r = 0.7) revealed CS (P < .001) and age (P = .003) were significant predictors of search performance. Performance of VI participants was normalized to the age-matched average performance of the NS group. In the VI group, it was found that children's normalized performance (52%) was better than both young (39%, P = .05) and older (40%, P = .048) adults. Unlike NS participants, young adults in the VI group may not have search ability superior to children with VI, despite having the same level of visual functions (quantified by visual acuity and CS). This could be because of vision impairment limiting the developmental acquisition of the age dividend for peak performance. Older adults in the VI group had the worst performance, indicating an interaction of aging.

Metatranscriptomic profiles of Eastern subterranean termites, Reticulitermes flavipes (Kollar) fed on second generation feedstocks.

PubMed

Rajarapu, Swapna Priya; Shreve, Jacob T; Bhide, Ketaki P; Thimmapuram, Jyothi; Scharf, Michael E

2015-04-22

Second generation lignocellulosic feedstocks are being considered as an alternative to first generation biofuels that are derived from grain starches and sugars. However, the current pre-treatment methods for second generation biofuel production are inefficient and expensive due to the recalcitrant nature of lignocellulose. In this study, we used the lower termite Reticulitermes flavipes (Kollar), as a model to identify potential pretreatment genes/enzymes specifically adapted for use against agricultural feedstocks. Metatranscriptomic profiling was performed on worker termite guts after feeding on corn stover (CS), soybean residue (SR), or 98% pure cellulose (paper) to identify (i) microbial community, (ii) pathway level and (iii) gene-level responses. Microbial community profiles after CS and SR feeding were different from the paper feeding profile, and protist symbiont abundance decreased significantly in termites feeding on SR and CS relative to paper. Functional profiles after CS feeding were similar to paper and SR; whereas paper and SR showed different profiles. Amino acid and carbohydrate metabolism pathways were downregulated in termites feeding on SR relative to paper and CS. Gene expression analyses showed more significant down regulation of genes after SR feeding relative to paper and CS. Stereotypical lignocellulase genes/enzymes were not differentially expressed, but rather were among the most abundant/constitutively-expressed genes. These results suggest that the effect of CS and SR feeding on termite gut lignocellulase composition is minimal and thus, the most abundantly expressed enzymes appear to encode the best candidate catalysts for use in saccharification of these and related second-generation feedstocks. Further, based on these findings we hypothesize that the most abundantly expressed lignocellulases, rather than those that are differentially expressed have the best potential as pretreatment enzymes for CS and SR feedstocks.

Impact of the Ability to Divide Attention on Reading Performance in Glaucoma.

PubMed

Swenor, Bonnielin K; Varadaraj, Varshini; Dave, Paulomi; West, Sheila K; Rubin, Gary S; Ramulu, Pradeep Y

2017-05-01

To determine if the ability to divide attention affects the relationship between glaucoma-related vision loss and reading speed. Better eye mean deviation (MD), contrast sensitivity (CS), and better-eye distance visual acuity (VA) were measured in 28 participants with glaucoma and 21 controls. Reading speeds were assessed using MNRead, IRest, and sustained silent reading tests (words per minute, wpm). The ability to divide attention was measured using the Brief Test of Attention (BTA; scored 0-10). Multivariable linear regression models were used to determine the relationship between visual factors and reading speeds. Effect modification by BTA score (low BTA: <7; high BTA: ≥7) was examined. Worse CS (per 0.1 log unit) was associated with slower maximum reading speed on MNRead test for participants with low BTA scores (β = -9 wpm; 95% confidence interval [CI]: -16, -2), but not for those with high BTA scores (β = -2 wpm; 95% CI: -6, +2). Similarly, for the IRest test, worse CS was associated with slower reading speeds (β = -12 wpm; 95% CI: -20, -4) among those with low, but not high BTA scores (β = -4 wpm; 95% CI: -10, +2). For the sustained silent reading test, glaucoma status (versus controls), worse visual field (VF) MD (per 5 dB), and worse CS were associated with 39%, 21%, and 19% slower reading speeds, respectively, for those with low BTA scores (P < 0.05), but these associations were not significant among those with high BTA scores (P > 0.1 for all). Decreased ability to divide attention, indicated by lower BTA scores, is associated with slower reading speeds in glaucoma with reduced CS and VF defects.

Impact of the Ability to Divide Attention on Reading Performance in Glaucoma

PubMed Central

Swenor, Bonnielin K.; Varadaraj, Varshini; Dave, Paulomi; West, Sheila K.; Rubin, Gary S.; Ramulu, Pradeep Y.

2017-01-01

Purpose To determine if the ability to divide attention affects the relationship between glaucoma-related vision loss and reading speed. Methods Better eye mean deviation (MD), contrast sensitivity (CS), and better-eye distance visual acuity (VA) were measured in 28 participants with glaucoma and 21 controls. Reading speeds were assessed using MNRead, IRest, and sustained silent reading tests (words per minute, wpm). The ability to divide attention was measured using the Brief Test of Attention (BTA; scored 0–10). Multivariable linear regression models were used to determine the relationship between visual factors and reading speeds. Effect modification by BTA score (low BTA: <7; high BTA: ≥7) was examined. Results Worse CS (per 0.1 log unit) was associated with slower maximum reading speed on MNRead test for participants with low BTA scores (β = −9 wpm; 95% confidence interval [CI]: −16, −2), but not for those with high BTA scores (β = −2 wpm; 95% CI: −6, +2). Similarly, for the IRest test, worse CS was associated with slower reading speeds (β = −12 wpm; 95% CI: −20, −4) among those with low, but not high BTA scores (β = −4 wpm; 95% CI: −10, +2). For the sustained silent reading test, glaucoma status (versus controls), worse visual field (VF) MD (per 5 dB), and worse CS were associated with 39%, 21%, and 19% slower reading speeds, respectively, for those with low BTA scores (P < 0.05), but these associations were not significant among those with high BTA scores (P > 0.1 for all). Conclusions Decreased ability to divide attention, indicated by lower BTA scores, is associated with slower reading speeds in glaucoma with reduced CS and VF defects. PMID:28460047

Organic solvent exposure and contrast sensitivity: comparing men and women

PubMed Central

Oliveira, A.R.; Campos, A.A.; de Andrade, M.J.O.; de Medeiros, P.C.B.; dos Santos, N.A.

2018-01-01

The goal of this study was to compare the visual contrast sensitivity (CS) of men and women exposed and not exposed to organic solvents. Forty-six volunteers of both genders aged between 18 and 41 years (mean±SD=27.72±6.28) participated. Gas station attendants were exposed to gas containing 46.30 ppm of solvents at a temperature of 304±274.39 K, humidity of 62.25±7.59% and ventilation of 0.69±0.46 m/s (a passive gas chromatography-based sampling method was used considering the microclimate variables). Visual CS was measured via the psychophysical method of two-alternative forced choice using vertical sinusoidal gratings with spatial frequencies of 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, and 16.0 cpd (cycles per degree) and an average luminance of 34.4 cd/m2. The results showed that visual CS was significantly lower (P<0.05) in the following groups: i) exposed men compared to unexposed men at frequencies of 0.2, 0.5, 1.0, and 2.0 cpd; ii) exposed women compared to unexposed women at a frequency of 5.0 cpd; and iii) exposed women compared to exposed men at a frequency of 0.5 cpd, even at exposures below the tolerance limit (300 ppm). These results suggest that the visual CS of exposed men was impaired over a wider range of spatial frequencies than that of exposed women. This difference may have been due to the higher body fat content of women compared to that of men, suggesting that body fat in women can serve as a protective factor against neurotoxic effects. PMID:29340521

Chondroitin Sulfate (CS) Lyases: Structure, Function and Application in Therapeutics.

PubMed

Rani, Aruna; Patel, Seema; Goyal, Arun

2018-01-01

Glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) are the chief natural polysaccharides which reside in biological tissues mainly in extracellular matrix. These CS along with adhesion molecules and growth factors are involved in central nervous system (CNS) development, cell progression and pathogenesis. The chondroitin lyases are the enzyme that degrade and alter the CS chains and hence modify various signalling pathways involving CS chains. These CS lyases are substrate specific, can precisely manipulate the CS polysaccharides and have various biotechnological, medical and therapeutic applications. These enzymes can be used to produce the unsaturated oligosaccharides, which have immune-modulatory, anti-inflammatory and neuroprotective properties. This review focuses on the major breakthrough of the chondroitin sulfate degrading enzymes, their structures and functioning mechanism. This also provides comprehensive information regarding production, purification, characterization of CS lyases and their major applications, both established as well as emerging ones such as neural development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Using Visual Technologies in the Introductory Programming Courses for Computer Science Majors

ERIC Educational Resources Information Center

Price, Kellie W.

2013-01-01

Decreasing enrollments, lower rates of student retention and changes in the learning styles of today's students are all issues that the Computer Science (CS) academic community is currently facing. As a result, CS educators are being challenged to find the right blend of technology and pedagogy for their curriculum in order to help students…

Expression of Clonorchis sinensis GIIIsPLA2 protein in baculovirus-infected insect cells and its overexpression facilitating epithelial-mesenchymal transition in Huh7 cells via AKT pathway.

PubMed

Shang, Mei; Xie, Zhizhi; Tang, Zeli; He, Lei; Wang, Xiaoyun; Wang, Caiqin; Wu, Yinjuan; Li, Ye; Zhao, Lu; Lv, Zhiyue; Wu, Zhongdao; Huang, Yan; Yu, Xinbing; Li, Xuerong

2017-04-01

Although prior studies confirmed that group III secretory phospholipase A 2 of Clonorchis sinensis (CsGIIIsPLA 2 ) had stimulating effect on liver fibrosis by binding to LX-2 cells, large-scale expression of recombinant protein and its function in the progression of hepatoma are worth exploring. Because of high productivity and low lipopolysaccharides (LPS) in the Sf9-baculovirus expression system, we firstly used this system to express the coding region of CsGIIIsPLA 2 . The molecular weight of recombinant CsGIIIsPLA 2 protein was about 34 kDa. Further investigation showed that most of the recombinant protein presented intracellular expression in Sf9 insect cell nucleus and could be detected only into cell debris, which made the protein purification and further functional study difficult. Therefore, to study the role of CsGIIIsPLA 2 in hepatocellular carcinoma (HCC) progression, CsGIIIsPLA 2 overexpression Huh7 cell model was applied. Cell proliferation, migration, and the expression level of epithelial-mesenchymal transition (EMT)-related molecules (E-cadherin, N-cadherin, α-catenin, Vimentin, p300, Snail, and Slug) along with possible mechanism were measured. The results indicated that CsGIIIsPLA 2 overexpression not only inhibited cell proliferation and promoted migration and EMT but also enhanced the phosphorylation of AKT in HCC cells. In conclusion, this study supported that CsGIIIsPLA 2 overexpression suppressed cell proliferation and induced EMT through the AKT pathway.

Cyclosporine a inhibits apoptosis of rat gingival epithelium.

PubMed

Ma, Su; Liu, Peihong; Li, Yanwu; Hou, Lin; Chen, Li; Qin, Chunlin

2014-08-01

The use of cyclosporine A (CsA) induces hyperplasia of the gingival epithelium in a site-specific response manner, but the molecular mechanism via which the lesion occurs is unclear. The present research aims to investigate the site-specific effect of CsA on the apoptosis of gingival epithelium associated with gingival hyperplasia. Forty Wistar rats were divided into CsA-treated and non-treated groups. Paraffin-embedded sections of mandibular first molars were selected for hematoxylin and eosin staining, immunohistochemistry analyses of bcl-2 and caspase-3, and the staining of terminal deoxynucleotidyl transfer-mediated dUTP nick-end labeling (TUNEL). The area of the whole gingival epithelium and the length of rete pegs were measured, and the number of bcl-2- and caspase-3-positive cells in the longest rete peg were counted. The analysis of variance for factorial designs and Fisher least significant difference test for post hoc analysis were used to determine the significance levels. In CsA-treated rats, bcl-2 expression was significantly upregulated, whereas caspase-3 expression was downregulated, along with a reduced number of TUNEL-positive cells. The site-specific distribution of bcl-2 was consistent with the site-specific hyperplasia of the gingival epithelium in CsA-treated rats. CsA inhibited gingival epithelial apoptosis via the mitochondrial pathway and common pathway. The antiapoptotic protein bcl-2 might play a critical role in the pathogenesis of the site-specific hyperplasia of gingival epithelium induced by CsA. There were mechanistic differences in the regulation of apoptosis for cells in the attached gingival epithelium, free gingival epithelium, and junctional epithelium.

Comparison of carbon-sulfur and carbon-amine bond in therapeutic drug: 4β-S-aromatic heterocyclic podophyllum derivatives display antitumor activity

PubMed Central

Li, Jian-Long; Zhao, Wei; Zhou, Chen; Zhang, Ya-Xuan; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

2015-01-01

Herein is a first effort to systematically study the significance of carbon-sulfur (C-S) and carbon-amine (C-NH) bonds on the antitumor proliferation activity of podophyllum derivatives and their precise mechanism of apoptosis. Compared with the derivative modified by a C-NH bond, the derivative modified by a C-S bond exhibited superior antitumor activity, the inhibition activity of target proteins tubulin or Topo II, cell cycle arrest, and apoptosis induction. Antitumor mechanistic studies showed that the death receptor and the mitochondrial apoptotic pathways were simultaneously activated by the C-S bond modified aromatic heterocyclic podophyllum derivatives with a higher cellular uptake percentage of 60–90% and induction of a higher level of reactive oxygen species (ROS). Only the mitochondrial apoptotic pathway was activated by the C-NH bond modified aromatic heterocyclic podophyllum derivatives, with a lower cellular uptake percentage of 40–50%. This study provided insight into effects of the C-S and C-NH bond modification on the improvement of the antitumor activity of Podophyllum derivatives. PMID:26443888

Solubility relations in the ternary system NaCl-CsCl-H2O at 1 atm. 1. Solubilities of halite from 20 to 100 °C

USGS Publications Warehouse

Chou, I.-Ming; Lee, R.D.

1983-01-01

Solubilities of halite in the ternary system NaCl-CsCl-H2O have been determined by the visual polythermal method at 1 atm from 20 to 100??C along five constant CsCl/(CsCl + H2O) weight ratio lines. These five constant weight ratios are 0.1, 0.2, 0.3, 0.4, and 0.5. The maximum uncertainties in these measurements are ??0.02 wt % NaCl and ??0.15??C. The data along each constant CsCl/(CsCl + H2O) weight ratio line were regressed to a smooth curve. The maximum deviation of the measured solubilities from the smooth curves is 0.06 wt % NaCl. Isothermal solubilities of halite were calculated from smoothed curves at 25, 50, and 75??C.

Decision making in asthma exacerbation: a clinical judgement analysis

PubMed Central

Jenkins, John; Shields, Mike; Patterson, Chris; Kee, Frank

2007-01-01

Background Clinical decisions which impact directly on patient safety and quality of care are made during acute asthma attacks by individual doctors based on their knowledge and experience. Decisions include administration of systemic corticosteroids (CS) and oral antibiotics, and admission to hospital. Clinical judgement analysis provides a methodology for comparing decisions between practitioners with different training and experience, and improving decision making. Methods Stepwise linear regression was used to select clinical cues based on visual analogue scale assessments of the propensity of 62 clinicians to prescribe a short course of oral CS (decision 1), a course of antibiotics (decision 2), and/or admit to hospital (decision 3) for 60 “paper” patients. Results When compared by specialty, paediatricians' models for decision 1 were more likely to include level of alertness as a cue (54% vs 16%); for decision 2 they were more likely to include presence of crepitations (49% vs 16%) and less likely to include inhaled CS (8% vs 40%), respiratory rate (0% vs 24%) and air entry (70% vs 100%). When compared to other grades, the models derived for decision 3 by consultants/general practitioners were more likely to include wheeze severity as a cue (39% vs 6%). Conclusions Clinicians differed in their use of individual cues and the number included in their models. Patient safety and quality of care will benefit from clarification of decision‐making strategies as general learning points during medical training, in the development of guidelines and care pathways, and by clinicians developing self‐awareness of their own preferences. PMID:17428817

Clonorchis sinensis lysophospholipase A upregulates IL-25 expression in macrophages as a potential pathway to liver fibrosis.

PubMed

Zhou, Lina; Shi, Mengchen; Zhao, Lu; Lin, Zhipeng; Tang, Zeli; Sun, Hengchang; Chen, Tingjin; Lv, Zhiyue; Xu, Jin; Huang, Yan; Yu, Xinbing

2017-06-17

Liver fibrosis is an excessive wound-healing reaction that requires the participation of inflammatory cells and hepatic stellate cells (HSCs). The pathogenesis of liver fibrosis caused by viruses and alcohol has been well characterized, but the molecular mechanisms underlying liver fibrosis induced by the liver fluke Clonorchis sinensis are poorly understood. Lysophospholipase A (LysoPLA), which deacylates lysophospholipids, plays a critical role in mediating the virulence and pathogenesis of parasites and fungi; however, the roles of C. sinensis lysophospholipase A (CsLysoPLA) in C. sinensis-induced liver fibrosis remain unknown. A mouse macrophage cell line (RAW264.7) was cultured and treated with CsLysoPLA. IL-25 and members of its associated signaling pathway were detected by performing quantitative real-time PCR, Western blotting and immunofluorescent staining. A human hepatic stellate cell line (LX-2) was cultured and exposed to IL-25. LX-2 cell activation markers were examined via quantitative real-time PCR, Western blotting and immunofluorescent staining. Migration was analyzed in transwell plates. Treating RAW264.7 cells with CsLysoPLA significantly induced IL-25 expression. Elevated PKA, B-Raf, and ERK1/2 mRNA levels and phosphorylated B-Raf and ERK1/2 were detected in CsLysoPLA-stimulated RAW264.7 cells. The PKA inhibitor H-89 weakened B-Raf and ERK1/2 phosphorylation whereas the AKT activator SC79 attenuated ERK1/2 phosphorylation in RAW264.7 cells. Both H-89 and SC79 inhibited CsLysoPLA-induced IL-25 upregulation. In addition, stimulation of LX-2 cells with IL-25 upregulated the expression of mesenchymal cell markers, including α-smooth muscle actin (α-SMA) and collagen type I (Collagen-I), and promoted cell migration. CsLysoPLA activates HSCs by upregulating IL-25 in macrophages through the PKA-dependent B-Raf/ERK1/2 pathway and potentially promotes hepatic fibrosis during C. sinensis infection.

The hexanoyl-CoA precursor for cannabinoid biosynthesis is formed by an acyl-activating enzyme in Cannabis sativa trichomes.

PubMed

Stout, Jake M; Boubakir, Zakia; Ambrose, Stephen J; Purves, Randy W; Page, Jonathan E

2012-08-01

The psychoactive and analgesic cannabinoids (e.g. Δ(9) -tetrahydrocannabinol (THC)) in Cannabis sativa are formed from the short-chain fatty acyl-coenzyme A (CoA) precursor hexanoyl-CoA. Cannabinoids are synthesized in glandular trichomes present mainly on female flowers. We quantified hexanoyl-CoA using LC-MS/MS and found levels of 15.5 pmol g(-1) fresh weight in female hemp flowers with lower amounts in leaves, stems and roots. This pattern parallels the accumulation of the end-product cannabinoid, cannabidiolic acid (CBDA). To search for the acyl-activating enzyme (AAE) that synthesizes hexanoyl-CoA from hexanoate, we analyzed the transcriptome of isolated glandular trichomes. We identified 11 unigenes that encoded putative AAEs including CsAAE1, which shows high transcript abundance in glandular trichomes. In vitro assays showed that recombinant CsAAE1 activates hexanoate and other short- and medium-chained fatty acids. This activity and the trichome-specific expression of CsAAE1 suggest that it is the hexanoyl-CoA synthetase that supplies the cannabinoid pathway. CsAAE3 encodes a peroxisomal enzyme that activates a variety of fatty acid substrates including hexanoate. Although phylogenetic analysis showed that CsAAE1 groups with peroxisomal AAEs, it lacked a peroxisome targeting sequence 1 (PTS1) and localized to the cytoplasm. We suggest that CsAAE1 may have been recruited to the cannabinoid pathway through the loss of its PTS1, thereby redirecting it to the cytoplasm. To probe the origin of hexanoate, we analyzed the trichome expressed sequence tag (EST) dataset for enzymes of fatty acid metabolism. The high abundance of transcripts that encode desaturases and a lipoxygenase suggests that hexanoate may be formed through a pathway that involves the oxygenation and breakdown of unsaturated fatty acids. © 2012 National Research Council of Canada. The Plant Journal © 2012 Blackwell Publishing Ltd.

The effect of withdrawal of visual presentation of errors upon the frequency spectrum of tremor in a manual task

PubMed Central

Sutton, G. G.; Sykes, K.

1967-01-01

1. When a subject attempts to exert a steady pressure on a joystick he makes small unavoidable errors which, irrespective of their origin or frequency, may be called tremor. 2. Frequency analysis shows that low frequencies always contribute much more to the total error than high frequencies. If the subject is not allowed to check his performance visually, but has to rely on sensations of pressure in the finger tips, etc., the error power spectrum plotted on logarithmic co-ordinates approximates to a straight line falling at 6 db/octave from 0·4 to 9 c/s. In other words the amplitude of the tremor component at each frequency is inversely proportional to frequency. 3. When the subject is given a visual indication of his errors on an oscilloscope the shape of the tremor spectrum alters. The most striking change is the appearance of a tremor peak at about 9 c/s, but there is also a significant increase of error in the range 1-4 c/s. The extent of these changes varies from subject to subject. 4. If the 9 c/s peak represents oscillation of a muscle length-servo it would appear that greater use is made of this servo when positional information is available from the eyes than when proprioceptive impulses from the limbs have to be relied on. ImagesFig. 2 PMID:6048997

Optimal Compressed Sensing and Reconstruction of Unstructured Mesh Datasets

DOE PAGES

Salloum, Maher; Fabian, Nathan D.; Hensinger, David M.; ...

2017-08-09

Exascale computing promises quantities of data too large to efficiently store and transfer across networks in order to be able to analyze and visualize the results. We investigate compressed sensing (CS) as an in situ method to reduce the size of the data as it is being generated during a large-scale simulation. CS works by sampling the data on the computational cluster within an alternative function space such as wavelet bases and then reconstructing back to the original space on visualization platforms. While much work has gone into exploring CS on structured datasets, such as image data, we investigate itsmore » usefulness for point clouds such as unstructured mesh datasets often found in finite element simulations. We sample using a technique that exhibits low coherence with tree wavelets found to be suitable for point clouds. We reconstruct using the stagewise orthogonal matching pursuit algorithm that we improved to facilitate automated use in batch jobs. We analyze the achievable compression ratios and the quality and accuracy of reconstructed results at each compression ratio. In the considered case studies, we are able to achieve compression ratios up to two orders of magnitude with reasonable reconstruction accuracy and minimal visual deterioration in the data. Finally, our results suggest that, compared to other compression techniques, CS is attractive in cases where the compression overhead has to be minimized and where the reconstruction cost is not a significant concern.« less

CsMAP34, a teleost MAP with dual role: A promoter of MASP-assisted complement activation and a regulator of immune cell activity.

PubMed

Li, Mo-Fei; Li, Jun; Sun, Li

2016-12-23

In teleost fish, the immune functions of mannan-binding lectin (MBL) associated protein (MAP) and MBL associated serine protease (MASP) are scarcely investigated. In the present study, we examined the biological properties both MAP (CsMAP34) and MASP (CsMASP1) molecules from tongue sole (Cynoglossus semilaevis). We found that CsMAP34 and CsMASP1 expressions occurred in nine different tissues and were upregulated by bacterial challenge. CsMAP34 protein was detected in blood, especially during bacterial infection. Recombinant CsMAP34 (rCsMAP34) bound C. semilaevis MBL (rCsBML) when the latter was activated by bacteria, while recombinant CsMASP1 (rCsMASP1) bound activated rCsBML only in the presence of rCsMAP34. rCsMAP34 stimulated the hemolytic and bactericidal activities of serum complement, whereas anti-CsMAP34 antibody blocked complement activities. Knockdown of CsMASP1 in C. semilaevis resulted in significant inhibition of complement activities. Furthermore, rCsMAP34 interacted directly with peripheral blood leukocytes (PBL) and enhanced the respiratory burst, acid phosphatase activity, chemotactic activity, and gene expression of PBL. These results indicate for the first time that a teleost MAP acts one hand as a regulator that promotes the lectin pathway of complement activation via its ability to recruit MBL to MASP, and other hand as a modulator of immune cell activity.

Comparison between bilateral implantation of a trifocal intraocular lens and blended implantation of two bifocal intraocular lenses

PubMed Central

Vilar, César; Hida, Wilson Takashi; de Medeiros, André Lins; Magalhães, Klayny Rafaella Pereira; de Moraes Tzelikis, Patrick Frensel; Chaves, Mario Augusto Pereira Dias; Motta, Antônio Francisco Pimenta; Carricondo, Pedro Carlos; Alves, Milton Ruiz; Nosé, Walton

2017-01-01

Purpose To compare visual outcomes and performance between bilateral implantation of a diffractive trifocal intraocular lens (IOL) Acrysof®PanOptix® TFNT00 and blended implantation of two different near add power bifocal IOLs: Acrysof® Restor® SV25T0 in dominant eye and Acrysof® Restor® SN6AD1 in the nondominant eye. Methods This prospective, nonrandomized, consecutive and comparative study assessed 20 patients (40 eyes) who had bilateral cataract surgery performed using the IOLs described. Patients were divided into groups, bilateral trifocal implant and blended implant. Evaluation included measurement of binocular uncorrected and corrected distance visual acuity at 4 m (UDVA, CDVA) and uncorrected intermediate (60 cm) and near (at 40 cm) visual acuity; contrast sensitivity (CS) and visual defocus curve. Results Postoperative CDVA comparison showed no statistical significance between groups. UDVA was significantly better in the trifocal groups. Under photopic conditions, the trifocal group had better CS in higher frequencies with and without glare. The binocular defocus curve demonstrated a trifocal behavior in both groups, with the bilateral trifocal group exhibiting better performance for intermediate vision. Conclusion Both lens combinations were able to provide good near, intermediate and distance vision, with the trifocal group showing significantly better performance at intermediate distances and better CS under photopic conditions. PMID:28814826

Onyx 18 embolisation of dural arteriovenous fistula via arterial and venous pathways: preliminary experience and evaluation of the short-term outcomes

PubMed Central

Long, X-A; Karuna, T; Zhang, X; Luo, B; Duan, C-Z

2012-01-01

Objective This paper mainly focuses on our preliminary experience and short-term outcome evaluation of embolisation of non-cavernous dural arteriovenous fistulas (ncsDAVFs) and cavernous sinus dural arteriovenous fistulas (csDAVFs) using Onyx 18 (ev3, Plymouth, MN), and in combination with coils, via arterial and venous approaches, respectively. Methods Between August 2008 and March 2010, 21 DAVFs (11 ncsDAVFs and 10 csDAVFs; age range: 28–68 years; 12 females and 9 males) were undertaken. Borden classification showed Type III in 1 and Type II in 10 ncsDAVFs, and Type II in 4 and Type I in 6 csDAVFs. Onyx 18 was used in 11 ncsDAVFs (10 via single feeder and 1 via 2 feeders). Onyx 18 or in combination with coils was used in 10 csDAVFs (9 via the inferior petrosal sinus and 1 via the superior ophthalmic vein). Results Total occlusion in immediate angiography was achieved in 18 cases (85.7%; 10 ncsDAVFs and 8 csDAVFs), and near-total occlusion in 1 ncsDAVF and 2 csDAVFs. Onyx 18 was migrated into normal vasculature in two ncsDAVFs without any sequelae. One csDAVF had VI cranial nerve palsy post-operatively, which completely recovered 2 weeks post-embolisation. Follow-up angiography at 3–12 months showed complete occlusion in 20 cases (95.2%; 10 ncsDAVFs and 10 csDAVFs). One ncsDAVF (4.8%) recurred after 3 months and was successfully re-embolised. Conclusion Preliminary results achieved after embolising 11 ncsDAVFs and 10 csDAVFs using Onyx 18 and in combination with coils via arterial and venous pathways, respectively, appeared to be safe, feasible and effective, as 95.2% of cases were totally occluded without any clinical sequelae. PMID:22374275

CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

PubMed

Zhou, You; Shan, Song; Li, Zhi-Bin; Xin, Li-Jun; Pan, De-Si; Yang, Qian-Jiao; Liu, Ying-Ping; Yue, Xu-Peng; Liu, Xiao-Rong; Gao, Ji-Zhou; Zhang, Jin-Wen; Ning, Zhi-Qiang; Lu, Xian-Ping

2017-03-01

Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC 50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R + cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration

PubMed Central

Selivanova, Alexandra; Shin, Hyun Joon; Miller, Joan W.; Jackson, Mary Lou

2018-01-01

Purpose Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. Methods We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. Results Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). Conclusion In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL. PMID:29746512

Visual acuity and contrast sensitivity are two important factors affecting vision-related quality of life in advanced age-related macular degeneration.

PubMed

Roh, Miin; Selivanova, Alexandra; Shin, Hyun Joon; Miller, Joan W; Jackson, Mary Lou

2018-01-01

Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL.

Anti-fibrotic effect of Cordyceps sinensis polysaccharide: Inhibiting HSC activation, TGF-β1/Smad signalling, MMPs and TIMPs.

PubMed

Peng, Jinghua; Li, Xuemei; Feng, Qin; Chen, Liang; Xu, Lili; Hu, Yiyang

2013-06-01

Cordyceps sinensis has been used to treat liver disease in traditional Chinese medicine for thousands of years. Polysaccharide extracted from cultured Cordyceps sinensis mycelia (CS-PS) is the major active components of cordyceps sinensis with anti-liver injury effects. In the present study, the effects of CS-PS on hepatic stellate cell (HSC) activation, transforming growth factor-β1 (TGF-β1)/Smad pathway, as well as matrix metalloproteinase (MMP) 2, MMP9 and tissue inhibitor of metalloproteinase (TIMP) 1, TIMP2, were investigated in liver fibrosis in rats induced by carbon tetrachloride (CCl4). Colchicine was used as a positive control. The effect of CS-PS inhibition liver injury and fibrosis was confirmed by decreasing serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, hepatic hydroxyproline and increasing serum albumin, as well as alleviation of histological changes, which was comparable to that of colchicine. With CS-PS treatment, hepatic α-smooth muscle actin, TGF-β1, TGF-β1 receptor (TβR)-I, TβR-II, p-Smad2, p-Smad3 and TIMP2 proteins expression were down-regulated comparing to that in CCl4 group. The activities of MMP2 and MMP9 in liver tissue were also inhibited in CS-PS-treated group. It is indicated that the effects of CS-PS anti-liver fibrosis are probably associated with the inhibition on HSC activation, TGF-β1/Smads signalling pathway, as well as MMP2, MMP9 activity and TIMP2 expression.

Differential Classical Conditioning Selectively Heightens Response Gain of Neural Population Activity in Human Visual Cortex

PubMed Central

Song, Inkyung; Keil, Andreas

2015-01-01

Neutral cues, after being reliably paired with noxious events, prompt defensive engagement and amplified sensory responses. To examine the neurophysiology underlying these adaptive changes, we quantified the contrast-response function of visual cortical population activity during differential aversive conditioning. Steady-state visual evoked potentials (ssVEPs) were recorded while participants discriminated the orientation of rapidly flickering grating stimuli. During each trial, luminance contrast of the gratings was slowly increased and then decreased. Right-tilted gratings (CS+) were paired with loud white noise but left-tilted gratings (CS−) were not. The contrast-following waveform envelope of ssVEPs showed selective amplification of the CS+ only during the high-contrast stage of the viewing epoch. Findings support the notion that motivational relevance, learned in a time frame of minutes, affects vision through a response gain mechanism. PMID:24981277

Neural pathways for visual speech perception

PubMed Central

Bernstein, Lynne E.; Liebenthal, Einat

2014-01-01

This paper examines the questions, what levels of speech can be perceived visually, and how is visual speech represented by the brain? Review of the literature leads to the conclusions that every level of psycholinguistic speech structure (i.e., phonetic features, phonemes, syllables, words, and prosody) can be perceived visually, although individuals differ in their abilities to do so; and that there are visual modality-specific representations of speech qua speech in higher-level vision brain areas. That is, the visual system represents the modal patterns of visual speech. The suggestion that the auditory speech pathway receives and represents visual speech is examined in light of neuroimaging evidence on the auditory speech pathways. We outline the generally agreed-upon organization of the visual ventral and dorsal pathways and examine several types of visual processing that might be related to speech through those pathways, specifically, face and body, orthography, and sign language processing. In this context, we examine the visual speech processing literature, which reveals widespread diverse patterns of activity in posterior temporal cortices in response to visual speech stimuli. We outline a model of the visual and auditory speech pathways and make several suggestions: (1) The visual perception of speech relies on visual pathway representations of speech qua speech. (2) A proposed site of these representations, the temporal visual speech area (TVSA) has been demonstrated in posterior temporal cortex, ventral and posterior to multisensory posterior superior temporal sulcus (pSTS). (3) Given that visual speech has dynamic and configural features, its representations in feedforward visual pathways are expected to integrate these features, possibly in TVSA. PMID:25520611

Biological proliferation of cesium-137 through the detrital food chain in a forest ecosystem in Japan

PubMed Central

Murakami, Masashi; Ohte, Nobuhito; Suzuki, Takahiro; Ishii, Nobuyoshi; Igarashi, Yoshiaki; Tanoi, Keitaro

2014-01-01

Radionuclides, including 137Cs, were released from the disabled Fukushima Daiichi Nuclear Power Plant and had been deposited broadly over forested areas of north-eastern Honshu Island, Japan. In the forest, 137Cs was highly concentrated on leaf litters deposited in autumn 2010, before the accident. Monitoring of the distribution of 137Cs among functional groups clearly showed the role of the detrital food chain as the primary channel of 137Cs transfer to consumer organisms. Although many studies have reported the bioaccumulation (or dilution) of radioactive materials through trophic interactions, the present results highlight the importance of examining multiple possible pathways (e.g., grazing vs. detrital chains) in the proliferation of 137Cs through food webs. These results provide important insight into the future distribution and transfer of 137Cs within forest ecosystems. PMID:24398571

2-Litre polyethylene glycol-citrate-simethicone plus bisacodyl versus 4-litre polyethylene glycol as preparation for colonoscopy in chronic constipation.

PubMed

Parente, Fabrizio; Vailati, Cristian; Bargiggia, Stefano; Manes, Gianpiero; Fontana, Paola; Masci, Enzo; Arena, Monica; Spinzi, Giancarlo; Baccarin, Alessandra; Mazzoleni, Giorgia; Testoni, Pier Alberto

2015-10-01

Chronic constipation is a risk factor of inadequate bowel preparation for colonoscopy; however, no large clinical trials have been performed in this subgroup of patients. To compare bowel cleansing efficacy, tolerability and acceptability of 2-L polyethylene-glycol-citrate-simethicone (PEG-CS) plus 2-day bisacodyl (reinforced regimen) vs. 4-L PEG in patients with chronic constipation undergoing colonoscopy. Randomized, observer-blind, parallel group study. Adult outpatients undergoing colonoscopy were randomly allocated to 2-L PEG-CS/bisacodyl or 4-L PEG, taken as split regimens before colonoscopy. Quality of bowel preparation was assessed by the Ottawa Bowel Cleansing Scale (OBCS). The amount of foam/bubble interfering with colonic visualization was also measured. 400 patients were enrolled. There was no significant difference in successful cleansing (OBCS score ≤6): 80.2% in the 2-L PEG-CS/bisacodyl vs. 81.4% in the 4-L PEG group. Significantly more patients taking 2L PEG-CS/bisacodyl showed no or minimal foam/bubbles in all colonic segments (80% vs. 63%; p<0.001). 2-L PEG-CS/bisacodyl was significantly more acceptable for ease of administration (p<0.001), willingness to repeat (p<0.001) and showed better compliance (p=0.002). Split 2-L PEG-CS plus bisacodyl was not superior to split 4-L PEG for colonoscopy bowel cleansing in patients with chronic constipation; however, it performed better than the standard regimen in terms of colonic mucosa visualization, patient acceptance and compliance. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway

PubMed Central

Hwang, Jae-Woong; Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.; Rahman, Irfan

2014-01-01

Patients with obstructive lung diseases display abnormal circadian rhythms in lung function. We determined the mechanism whereby environmental tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1, through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung function, and inflammatory and emphysematous responses in the lungs. CS exposure (100–300 mg/m3 particulates) altered clock gene expression and reduced locomotor activity by disrupting the central and peripheral clocks and increased lung inflammation, causing emphysema in mice. BMAL1 was acetylated and degraded in the lungs of mice exposed to CS and in patients with chronic obstructive pulmonary disease (COPD), compared with lungs of the nonsmoking controls, linking it mechanistically to CS-induced reduction of SIRT1. Targeted deletion of Bmal1 in lung epithelium augmented inflammation in response to CS, which was not attenuated by the selective SIRT1 activator SRT1720 (EC50=0.16 μM) in these mice. Thus, the circadian clock, specifically the enhancer BMAL1 in epithelium, plays a pivotal role, mediated by SIRT1-dependent BMAL1, in the regulation of CS-induced lung inflammatory and injurious responses.— Hwang, J.-W., Sundar, I. K., Yao, H., Sellix, M. T., Rahman, I. Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway. PMID:24025728

A Pilot Study Linking Endothelial Injury in Lungs and Kidneys in Chronic Obstructive Pulmonary Disease

PubMed Central

Laucho-Contreras, Maria E.; Petersen, Hans; Bijol, Vanesa; Sholl, Lynette M.; Choi, Mary E.; Divo, Miguel; Pinto-Plata, Victor; Chetta, Alfredo; Tesfaigzi, Yohannes; Celli, Bartolomé R.

2017-01-01

Rationale: Patients with chronic obstructive pulmonary disease (COPD) frequently have albuminuria (indicative of renal endothelial cell injury) associated with hypoxemia. Objectives: To determine whether (1) cigarette smoke (CS)-induced pulmonary and renal endothelial cell injury explains the association between albuminuria and COPD, (2) CS-induced albuminuria is linked to increases in the oxidative stress–advanced glycation end products (AGEs) receptor for AGEs (RAGE) pathway, and (3) enalapril (which has antioxidant properties) limits the progression of pulmonary and renal injury by reducing activation of the AGEs–RAGE pathway in endothelial cells in both organs. Methods: In 26 patients with COPD, 24 ever-smokers without COPD, 32 nonsmokers who underwent a renal biopsy or nephrectomy, and in CS-exposed mice, we assessed pathologic and ultrastructural renal lesions, and measured urinary albumin/creatinine ratios, tissue oxidative stress levels, and AGEs and RAGE levels in pulmonary and renal endothelial cells. The efficacy of enalapril on pulmonary and renal lesions was assessed in CS-exposed mice. Measurements and Main Results: Patients with COPD and/or CS-exposed mice had chronic renal injury, increased urinary albumin/creatinine ratios, and increased tissue oxidative stress and AGEs-RAGE levels in pulmonary and renal endothelial cells. Treating mice with enalapril attenuated CS-induced increases in urinary albumin/creatinine ratios, tissue oxidative stress levels, endothelial cell AGEs and RAGE levels, pulmonary and renal cell apoptosis, and the progression of chronic renal and pulmonary lesions. Conclusions: Patients with COPD and/or CS-exposed mice have pulmonary and renal endothelial cell injury linked to increased endothelial cell AGEs and RAGE levels. Albuminuria could identify patients with COPD in whom angiotensin-converting enzyme inhibitor therapy improves renal and lung function by reducing endothelial injury. PMID:28085500

Endoplasmic reticulum chaperone GRP78 mediates cigarette smoke-induced necroptosis and injury in bronchial epithelium.

PubMed

Wang, Yong; Zhou, Jie-Sen; Xu, Xu-Chen; Li, Zhou-Yang; Chen, Hai-Pin; Ying, Song-Min; Li, Wen; Shen, Hua-Hao; Chen, Zhi-Hua

2018-01-01

Bronchial epithelial cell death and airway inflammation induced by cigarette smoke (CS) have been involved in the pathogenesis of COPD. GRP78, belonging to heat shock protein 70 family, has been implicated in cell death and inflammation, while little is known about its roles in COPD. Here, we demonstrate that GRP78 regulates CS-induced necroptosis and injury in bronchial epithelial cells. GRP78 and necroptosis markers were examined in human bronchial epithelial (HBE) cell line, primary mouse tracheal epithelial cells, and mouse lungs. siRNA targeting GRP78 gene and necroptosis inhibitor were used. Expression of inflammatory cytokines, mucin MUC5AC, and related signaling pathways were detected. Exposure to CS significantly increased the expression of GRP78 and necroptosis markers in HBE cell line, primary mouse tracheal epithelial cells, and mouse lungs. Inhibition of GRP78 significantly suppressed CS extract (CSE)-induced necroptosis. Furthermore, GRP78-necroptosis cooperatively regulated CSE-induced inflammatory cytokines such as interleukin 6 (IL6), IL8, and mucin MUC5AC in HBE cells, likely through the activation of nuclear factor (NF-κB) and activator protein 1 (AP-1) pathways, respectively. Taken together, our results demonstrate that GRP78 promotes CSE-induced inflammatory response and mucus hyperproduction in airway epithelial cells, likely through upregulation of necroptosis and subsequent activation of NF-κB and AP-1 pathways. Thus, inhibition of GRP78 and/or inhibition of necroptosis could be the effective therapeutic approaches for the treatment of COPD.

Clinical audits: A practical strategy for reducing cesarean section rates in a general hospital in Tehran, Iran.

PubMed

Mohammadi, Soheila; Källestål, Carina; Essén, Birgitta

2012-01-01

To investigate whether the introduction of clinical audits by the Safe Motherhood Committee of a general hospital in Tehran, Iran, influenced cesarean section (CS) rates, A retrospective study was performed. The number of deliveries before and after the institution of clinical audits (May to December 2005) were tabulated in the audited hospital and analyzed by Chi(2) test. Additionally, CS rates were measured in 3 other general hospitals during the same time period for comparison. A total of 3,494 deliveries were recorded during the study periods in 2004 and 2005 at the audited hospital. Subsequent to the audit, the overall CS rate decreased from 40% to 33% (p < 0.001) and the primary CS rate from 29% to 21% (p < 0.001), accounting for a 27% reduction in the risk of primary CS. In 2006 CS rates reverted to 42%. None of the other 3 general hospitals indicated a decline in CS rates in 2005. Our findings show a preventive association between the clinical audits and CS rates in a general hospital. The implementation of a clinical audit process can be an effective way to track care pathways and reduce unnecessary CS deliveries.

The Level of Vision Necessary for Competitive Performance in Rifle Shooting: Setting the Standards for Paralympic Shooting with Vision Impairment.

PubMed

Allen, Peter M; Latham, Keziah; Mann, David L; Ravensbergen, Rianne H J C; Myint, Joy

2016-01-01

The aim of this study was to investigate the level of vision impairment (VI) that would reduce performance in shooting; to guide development of entry criteria to visually impaired (VI) shooting. Nineteen international-level shooters without VI took part in the study. Participants shot an air rifle, while standing, toward a regulation target placed at the end of a 10 m shooting range. Cambridge simulation glasses were used to simulate six different levels of VI. Visual acuity (VA) and contrast sensitivity (CS) were assessed along with shooting performance in each of seven conditions of simulated impairment and compared to that with habitual vision. Shooting performance was evaluated by calculating each individual's average score in every level of simulated VI and normalizing this score by expressing it as a percentage of the baseline performance achieved with habitual vision. Receiver Operating Characteristic curves were constructed to evaluate the ability of different VA and CS cut-off criteria to appropriately classify these athletes as achieving 'expected' or 'below expected' shooting results based on their performance with different levels of VA and CS. Shooting performance remained relatively unaffected by mild decreases in VA and CS, but quickly deteriorated with more moderate losses. The ability of visual function measurements to classify shooting performance was good, with 78% of performances appropriately classified using a cut-off of 0.53 logMAR and 74% appropriately classified using a cut-off of 0.83 logCS. The current inclusion criteria for VI shooting (1.0 logMAR) is conservative, maximizing the chance of including only those with an impairment that does impact performance, but potentially excluding some who do have a genuine impairment in the sport. A lower level of impairment would include more athletes who do have a genuine impairment but would potentially include those who do not actually have an impairment that impacts performance in the sport. An impairment to CS could impact performance in the sport and might be considered in determining eligibility to take part in VI competition.

The Level of Vision Necessary for Competitive Performance in Rifle Shooting: Setting the Standards for Paralympic Shooting with Vision Impairment

PubMed Central

Allen, Peter M.; Latham, Keziah; Mann, David L.; Ravensbergen, Rianne H. J. C.; Myint, Joy

2016-01-01

The aim of this study was to investigate the level of vision impairment (VI) that would reduce performance in shooting; to guide development of entry criteria to visually impaired (VI) shooting. Nineteen international-level shooters without VI took part in the study. Participants shot an air rifle, while standing, toward a regulation target placed at the end of a 10 m shooting range. Cambridge simulation glasses were used to simulate six different levels of VI. Visual acuity (VA) and contrast sensitivity (CS) were assessed along with shooting performance in each of seven conditions of simulated impairment and compared to that with habitual vision. Shooting performance was evaluated by calculating each individual’s average score in every level of simulated VI and normalizing this score by expressing it as a percentage of the baseline performance achieved with habitual vision. Receiver Operating Characteristic curves were constructed to evaluate the ability of different VA and CS cut-off criteria to appropriately classify these athletes as achieving ‘expected’ or ‘below expected’ shooting results based on their performance with different levels of VA and CS. Shooting performance remained relatively unaffected by mild decreases in VA and CS, but quickly deteriorated with more moderate losses. The ability of visual function measurements to classify shooting performance was good, with 78% of performances appropriately classified using a cut-off of 0.53 logMAR and 74% appropriately classified using a cut-off of 0.83 logCS. The current inclusion criteria for VI shooting (1.0 logMAR) is conservative, maximizing the chance of including only those with an impairment that does impact performance, but potentially excluding some who do have a genuine impairment in the sport. A lower level of impairment would include more athletes who do have a genuine impairment but would potentially include those who do not actually have an impairment that impacts performance in the sport. An impairment to CS could impact performance in the sport and might be considered in determining eligibility to take part in VI competition. PMID:27877150

A patient with Alzheimer's disease complicated by elderly-onset Cushing's syndrome who had undergone surgical treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia.

PubMed

Haraguchi, Yoshinori; Mizoguchi, Yoshito; Noguchi, Tomoyuki; Arai, Takeo; Fukuyama, Junko; Kato, Takahiro A; Kawashima, Toshiro; Monji, Akira

2016-07-01

Cushing's syndrome (CS) is a rare disorder, especially in older people. Loss of brain volume and neurocognitive impairment of varying degrees has been demonstrated in patients with CS. However, there is a large difference between the median age of presentation of CS and that of Alzheimer's disease. We herein report a case of a patient with Alzheimer's disease complicated by elderly-onset CS who had undergone surgical treatment for adrenal hyperplasia. Surgical correction of hypercortisolism seems to have slowed the progression of brain volume loss and cognitive dysfunction and improved psychiatric symptoms such as visual hallucination, restlessness, and psychomotor excitement. These improvements have remarkably reduced the burden on the patient's caregivers. The present case suggests that subclinical CS may be present, particularly in rapidly progressive dementia, and that surgical treatment of CS for neuropsychiatric symptoms is useful. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

Post-Extinction Conditional Stimulus Valence Predicts Reinstatement Fear: Relevance for Long Term Outcomes of Exposure Therapy

PubMed Central

Zbozinek, Tomislav D.; Hermans, Dirk; Prenoveau, Jason M.; Liao, Betty; Craske, Michelle G.

2014-01-01

Exposure therapy for anxiety disorders is translated from fear conditioning and extinction. While exposure therapy is effective in treating anxiety, fear sometimes returns after exposure. One pathway for return of fear is reinstatement: unsignaled unconditional stimuli following completion of extinction. The present study investigated the extent to which valence of the conditional stimulus (CS+) after extinction predicts return of CS+ fear after reinstatement. Participants (N = 84) engaged in a differential fear conditioning paradigm and were randomized to reinstatement or non-reinstatement. We hypothesized that more negative post-extinction CS+ valence would predict higher CS+ fear after reinstatement relative to non-reinstatement and relative to extinction retest. Results supported the hypotheses and suggest that strategies designed to decrease negative valence of the CS+ may reduce the return of fear via reinstatement following exposure therapy. PMID:24957680

Metabolic Pathways Visualization Skills Development by Undergraduate Students

ERIC Educational Resources Information Center

dos Santos, Vanessa J. S. V.; Galembeck, Eduardo

2015-01-01

We have developed a metabolic pathways visualization skill test (MPVST) to gain greater insight into our students' abilities to comprehend the visual information presented in metabolic pathways diagrams. The test is able to discriminate students' visualization ability with respect to six specific visualization skills that we identified as key to…

Non-Invasive Visualization and Quantitation of Cardiovascular Structure and Function.

ERIC Educational Resources Information Center

Ritman, E. L.; And Others

1979-01-01

Described is a new approach to investigative physiology based on computerized transaxial tomography, in which visualization and measurement of the internal structure of the cardiopulmonary system is possible without postmortem, biopsy, or vivisection procedures. Examples are given for application of the Dynamic Spatial Reconstructor (DSR). (CS)

In vitro systems toxicology approach to investigate the effects of repeated cigarette smoke exposure on human buccal and gingival organotypic epithelial tissue cultures.

PubMed

Schlage, Walter K; Iskandar, Anita R; Kostadinova, Radina; Xiang, Yang; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Frentzel, Stefan; Talikka, Marja; Geertz, Marcel; Mathis, Carole; Ivanov, Nikolai; Hoeng, Julia; Peitsch, Manuel C

2014-10-01

Smoking has been associated with diseases of the lung, pulmonary airways and oral cavity. Cytologic, genomic and transcriptomic changes in oral mucosa correlate with oral pre-neoplasia, cancer and inflammation (e.g. periodontitis). Alteration of smoking-related gene expression changes in oral epithelial cells is similar to that in bronchial and nasal epithelial cells. Using a systems toxicology approach, we have previously assessed the impact of cigarette smoke (CS) seen as perturbations of biological processes in human nasal and bronchial organotypic epithelial culture models. Here, we report our further assessment using in vitro human oral organotypic epithelium models. We exposed the buccal and gingival organotypic epithelial tissue cultures to CS at the air-liquid interface. CS exposure was associated with increased secretion of inflammatory mediators, induction of cytochrome P450s activity and overall weak toxicity in both tissues. Using microarray technology, gene-set analysis and a novel computational modeling approach leveraging causal biological network models, we identified CS impact on xenobiotic metabolism-related pathways accompanied by a more subtle alteration in inflammatory processes. Gene-set analysis further indicated that the CS-induced pathways in the in vitro buccal tissue models resembled those in the in vivo buccal biopsies of smokers from a published dataset. These findings support the translatability of systems responses from in vitro to in vivo and demonstrate the applicability of oral organotypical tissue models for an impact assessment of CS on various tissues exposed during smoking, as well as for impact assessment of reduced-risk products.

In vitro systems toxicology approach to investigate the effects of repeated cigarette smoke exposure on human buccal and gingival organotypic epithelial tissue cultures

PubMed Central

Schlage, Walter K.; Kostadinova, Radina; Xiang, Yang; Sewer, Alain; Majeed, Shoaib; Kuehn, Diana; Frentzel, Stefan; Talikka, Marja; Geertz, Marcel; Mathis, Carole; Ivanov, Nikolai; Hoeng, Julia; Peitsch, Manuel C.

2014-01-01

Smoking has been associated with diseases of the lung, pulmonary airways and oral cavity. Cytologic, genomic and transcriptomic changes in oral mucosa correlate with oral pre-neoplasia, cancer and inflammation (e.g. periodontitis). Alteration of smoking-related gene expression changes in oral epithelial cells is similar to that in bronchial and nasal epithelial cells. Using a systems toxicology approach, we have previously assessed the impact of cigarette smoke (CS) seen as perturbations of biological processes in human nasal and bronchial organotypic epithelial culture models. Here, we report our further assessment using in vitro human oral organotypic epithelium models. We exposed the buccal and gingival organotypic epithelial tissue cultures to CS at the air–liquid interface. CS exposure was associated with increased secretion of inflammatory mediators, induction of cytochrome P450s activity and overall weak toxicity in both tissues. Using microarray technology, gene-set analysis and a novel computational modeling approach leveraging causal biological network models, we identified CS impact on xenobiotic metabolism-related pathways accompanied by a more subtle alteration in inflammatory processes. Gene-set analysis further indicated that the CS-induced pathways in the in vitro buccal tissue models resembled those in the in vivo buccal biopsies of smokers from a published dataset. These findings support the translatability of systems responses from in vitro to in vivo and demonstrate the applicability of oral organotypical tissue models for an impact assessment of CS on various tissues exposed during smoking, as well as for impact assessment of reduced-risk products. PMID:25046638

Receptor-mediated transcytosis of cyclophilin B through the blood-brain barrier.

PubMed

Carpentier, M; Descamps, L; Allain, F; Denys, A; Durieux, S; Fenart, L; Kieda, C; Cecchelli, R; Spik, G

1999-07-01

Cyclophilin B (CyPB) is a cyclosporin A (CsA)-binding protein mainly located in intracellular vesicles and secreted in biological fluids. In previous works, we demonstrated that CyPB interacts with T lymphocytes and enhances in vitro cellular incorporation and activity of CsA. In addition to its immunosuppressive activity, CsA is able to promote regeneration of damaged peripheral nerves. However, the crossing of the drug from plasma to neural tissue is restricted by the relative impermeability of the blood-brain barrier. To know whether CyPB might also participate in the delivery of CsA into the brain, we have analyzed the interactions of CyPB with brain capillary endothelial cells. First, we demonstrated that CyPB binds to two types of binding sites present at the surface of capillary endothelial cells from various species of tissues. The first type of binding sites (K(D) = 300 nM; number of sites = 3 x 10(6)) is related to interactions with negatively charged compounds such as proteoglycans. The second type of binding sites, approximately 50,000 per cell, exhibits a higher affinity for CyPB (K(D) = 15 nM) and is involved in an endocytosis process, indicating it might correspond to a functional receptor. Finally, the use of an in vitro model of blood-brain barrier allowed us to demonstrate that CyPB is transcytosed by a receptor-mediated pathway (flux = 16.5 fmol/cm2/h). In these conditions, CyPB did not significantly modify the passage of CsA, indicating that it is unlikely to provide a pathway for CsA brain delivery.

Quantitative proteomics reveals molecular mechanism of gamabufotalin and its potential inhibition on Hsp90 in lung cancer.

PubMed

Zhang, Liyuan; Yu, Zhenlong; Wang, Yan; Wang, Xiaobo; Zhang, Lianru; Wang, Chao; Yue, Qingxi; Wang, Xun; Deng, Sa; Huo, Xiaokui; Tian, Xiangge; Huang, Shanshan; Zhang, Baojing; Ma, Xiaochi

2016-11-22

Gamabufotalin (CS-6) is a major bufadienolide of Chansu, which shows desirable metabolic stability and less adverse effect in cancer therapy. CS-6 treatment inhibited the proliferation of NSCLC in a nanomolar range. And CS-6 could induce G2/M cell cycle arrest and apoptosis in A549 cells. However, its molecular mechanism in antitumor activity remains poorly understood. We employed a quantitative proteomics approach to identify the potential cellular targets of CS-6, and found 38 possible target-related proteins. Among them, 31 proteins were closely related in the protein-protein interaction network. One of the regulatory nodes in key pathways was occupied by Hsp90. Molecular docking revealed that CS-6 interacted with the ATP-binding sites of Hsp90. In addition, CS-6 inhibited the chaperone function of Hsp90 and reduced expression of Hsp90-dependent client proteins. Moreover, CS-6 markedly down-regulated the protein level of Hsp90 in tumor tissues of the xenograft mice. Taken together, our results suggest that CS-6 might be a novel inhibitor of Hsp90, and the possible network associated with CS-6 target-related proteins was constructed, which provided experimental evidence for the preclinical value of using CS-6 as an effective antitumor agent in treatment of NSCLC.

Analysis of repair and PCNA complex formation induced by ionizing radiation in human fibroblast cell lines.

PubMed

Karmakar, P; Balajee, A S; Natarajan, A T

2001-05-01

Proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA polymerase delta and epsilon, is involved in both DNA replication and repair. Previous studies in vitro have demonstrated the requirement of PCNA in the resynthesis step of nucleotide excision repair (NER) and base excision repair (BER). Using a native chromatin template isolated under near physiological conditions, we have analysed the involvement of PCNA in the BER pathway in different NER defective human cell lines. The repair sites and PCNA were visualized by indirect immunolabelling followed by fluorescence microscopy. The results indicate that exposure to X-rays triggers the induction of PCNA in all the three human fibroblast cell lines studied, namely normal, xeroderma pigmentosum group A (XP-A) and Cockayne syndrome group B (CS-B). In all the cell lines, induction of PCNA and repair patches occurred in a dose- and time-dependent fashion. Induction of repair patches in NER-deficient XP-A cells suggests that the X-ray-induced lesions are largely repaired via the BER pathway involving PCNA as one of the key components of this pathway. X-ray-induced repair synthesis was greatly inhibited by treatment of cells with DNA polymerase inhibitors aphidicolin and cytosine arabinoside. Interestingly, inhibition of repair resynthesis did not affect the intensity of PCNA staining in X-irradiated cells indicating that the PCNA may be required for the BER pathway at a step preceding the resynthesis step.

Molecular and Biochemical Basis for Stress-Induced Accumulation of Free and Bound p-Coumaraldehyde in Cucumber1[W][OA

PubMed Central

Varbanova, Marina; Porter, Katie; Lu, Fachuang; Ralph, John; Hammerschmidt, Ray; Jones, A. Daniel; Day, Brad

2011-01-01

To elucidate the genetic and biochemical regulation of elicitor-induced p-coumaraldehyde accumulation in plants, we undertook a multifaceted approach to characterize the metabolic flux through the phenylpropanoid pathway via the characterization and chemical analysis of the metabolites in the p-coumaryl, coniferyl, and sinapyl alcohol branches of this pathway. Here, we report the identification and characterization of four cinnamyl alcohol dehydrogenases (CADs) from cucumber (Cucumis sativus) with low activity toward p-coumaraldehyde yet exhibiting significant activity toward other phenylpropanoid hydroxycinnamaldehydes. As part of this analysis, we identified and characterized the activity of a hydroxycinnamoyl-coenzyme A:shikimate hydroxycinnamoyl transferase (HCT) capable of utilizing shikimate and p-coumaroyl-coenzyme A to generate p-coumaroyl shikimate. Following pectinase treatment of cucumber, we observed the rapid accumulation of p-coumaraldehyde, likely the result of low aldehyde reductase activity (i.e. alcohol dehydrogenase in the reverse reaction) of CsCAD enzymes on p-coumaraldehyde. In parallel, we noted a concomitant reduction in the activity of CsHCT. Taken together, our findings support the hypothesis that the up-regulation of the phenylpropanoid pathway upon abiotic stress greatly enhances the overall p-coumaryl alcohol branch of the pathway. The data presented here point to a role for CsHCT (as well as, presumably, p-coumarate 3-hydroxylase) as a control point in the regulation of the coniferyl and sinapyl alcohol branches of this pathway. This mechanism represents a potentially evolutionarily conserved process to efficiently and quickly respond to biotic and abiotic stresses in cucurbit plants, resulting in the rapid lignification of affected tissues. PMID:21940999

Cigarette smoke increases Staphylococcus aureus biofilm formation via oxidative stress.

PubMed

Kulkarni, Ritwij; Antala, Swati; Wang, Alice; Amaral, Fábio E; Rampersaud, Ryan; Larussa, Samuel J; Planet, Paul J; Ratner, Adam J

2012-11-01

The strong epidemiological association between cigarette smoke (CS) exposure and respiratory tract infections is conventionally attributed to immunosuppressive and irritant effects of CS on human cells. Since pathogenic bacteria such as Staphylococcus aureus are members of the normal microbiota and reside in close proximity to human nasopharyngeal cells, we hypothesized that bioactive components of CS might affect these organisms and potentiate their virulence. Using Staphylococcus aureus as a model organism, we observed that the presence of CS increased both biofilm formation and host cell adherence. Analysis of putative molecular pathways revealed that CS exposure decreased expression of the quorum-sensing agr system, which is involved in biofilm dispersal, and increased transcription of biofilm inducers such as sarA and rbf. CS contains bioactive compounds, including free radicals and reactive oxygen species, and we observed transcriptional induction of bacterial oxidoreductases, including superoxide dismutase, following exposure. Moreover, pretreatment of CS with an antioxidant abrogated CS-mediated enhancement of biofilms. Exposure of bacteria to hydrogen peroxide alone increased biofilm formation. These observations are consistent with the hypothesis that CS induces staphylococcal biofilm formation in an oxidant-dependent manner. CS treatment induced transcription of fnbA (encoding fibronectin binding protein A), leading to increased binding of CS-treated staphylococci to immobilized fibronectin and increased adherence to human cells. These observations indicate that the bioactive effects of CS may extend to the resident microbiota of the nasopharynx, with implications for the pathogenesis of respiratory infection in CS-exposed humans.

Crystalens HD intraocular lens analysis using an adaptive optics visual simulator.

PubMed

Pérez-Vives, Cari; Montés-Micó, Robert; López-Gil, Norberto; Ferrer-Blasco, Teresa; García-Lázaro, Santiago

2013-12-01

To compare visual and optical quality of the Crystalens HD intraocular lens (IOL) with that of a monofocal IOL. The wavefront aberration patterns of the monocular Akreos Adapt AO IOL and the single-optic accommodating Crystalens HD IOL were measured in a model eye. The Crystalens IOL was measured in its nonaccommodative state and then, after flexing the haptic to produce 1.4 mm of movement, in its accommodative state. Using an adaptive optics system, subjects' aberrations were removed and replaced with those of pseudophakes viewing with either lens. Monocular distance visual acuity (DVA) at high (100%), medium (50%), and low (10%) contrast and contrast sensitivity (CS) were measured for both IOL optics. Near VA (NVA) and CS were measured for the Crystalens HD IOL in its accommodative state. Depth of focus around the distance and near focus was also evaluated for the Crystalens HD IOL. Modulation transfer function (MTF), point spread function (PSF), and Strehl ratio were also calculated. All measures were taken for 3- and 5-mm pupils. The MTF, PSF, and Strehl ratio showed comparable values between IOLs (p > 0.05). There were no significant differences in DVA and CS between IOLs for all contrasts and pupils (p > 0.05). When spherically focused, mean DVA and NVA with the Crystalens HD IOL were ≥20/20 at 100 and 50% contrasts for both pupils. Monocular DVA, NVA, and CS were slightly better with 3- than 5-mm pupils, but without statistically significant differences. The Crystalens HD IOL showed about 0.75 and 0.50 D of depth of focus in its accommodative state and nonaccommodative state, respectively. The optical and visual quality with the nonaccommodatied Crystalens HD IOL was comparable to that of a monofocal IOL. If this lens can move 1.4 mm in the eye, it will provide high-quality optics for near vision as well.

Myeloid-Derived Suppressor Cells Ameliorate Cyclosporine A-Induced Hypertension in Mice.

PubMed

Chiasson, Valorie L; Bounds, Kelsey R; Chatterjee, Piyali; Manandhar, Lochana; Pakanati, Abhinandan R; Hernandez, Marcos; Aziz, Bilal; Mitchell, Brett M

2018-01-01

The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice. Daily interleukin-33 treatment, which increased MDSC levels, completely prevented CsA-induced hypertension and vascular and renal toxicity. Adoptive transfer of MDSCs from control mice into CsA-treated mice after hypertension was established dose-dependently reduced blood pressure and vascular and glomerular injury. CsA treatment of aortas and kidneys isolated from control mice for 24 hours decreased relaxation responses and increased inflammation, respectively, and these effects were prevented by the presence of MDSCs. MDSCs also prevented the CsA-induced increase in fibronectin in microvascular and glomerular endothelial cells. Last, CsA dose-dependently reduced the number of MDSCs by inhibiting calcineurin and preventing cell proliferation, as other direct calcineurin signaling pathway inhibitors had the same dose-dependent effect. These data suggest that augmenting MDSCs can reduce the cardiovascular and renal toxicity and hypertension caused by CsA. © 2017 American Heart Association, Inc.

Clinical implications of parallel visual pathways.

PubMed

Bassi, C J; Lehmkuhle, S

1990-02-01

Visual information travels from the retina to visual cortical areas along at least two parallel pathways. In this paper, anatomical and physiological evidence is presented to demonstrate the existence of, and trace these two pathways throughout the visual systems of the cat, primate, and human. Physiological and behavioral experiments are discussed which establish that these two pathways are differentially sensitive to stimuli that vary in spatial and temporal frequency. One pathway (M-pathway) is more sensitive to coarse visual form that is modulated or moving at fast rates, whereas the other pathway (P-pathway) is more sensitive to spatial detail that is stationary or moving at slow rates. This difference between the M- and P-pathways is related to some spatial and temporal effects observed in humans. Furthermore, evidence is presented that certain diseases selectively comprise the functioning of M- or P-pathways (i.e., glaucoma, Alzheimer's disease, and anisometropic amblyopia), and some of the spatial and temporal deficits observed in these patients are presented within the context of the dysfunction of the M- or P-pathway.

Molecular characterization and expression of Rab7 from Clonorchis sinensis and its potential role in autophagy.

PubMed

Jia, Feifei; Li, Ye; Huang, Yan; Chen, Tingjin; Li, Shan; Xu, Yanquan; Wu, Zhongdao; Li, Xuerong; Yu, Xinbing

2013-07-01

Accumulating evidences suggest that Rab7 GTPase is important for the normal progression of autophagy. However, the role of Rab7 GTPase in regulation of autophagy in Clonorchis sinensis is not known. In this study, a gene encoding Rab7 was isolated from C. sinensis adult cDNA. Recombinant CsRab7 was expressed and purified from Escherichia coli. CsRab7 transcripts were detected in the cDNA of adult worm, metacercaria, cercaria, and egg of C. sinensis, and were highly expressed in the metacercaria. Immunohistochemical localization results revealed that CsRab7 was specifically deposited on the vitellarium and eggs of adult worm. Furthermore, EGFP signal of CsRab7WT and the active mutant CsRab7Q67L were associated with autophagic vesicles in transiently transfected 293T cells. It is concluded from the present study that CsRab7 GTPase possibly contributes to the development of C. sinensis and that the autophagy pathway could be an important site of action with respect to the developmental role of CsRab7 in C. sinensis.

Modeling and Simulation of the Visual Effects of Colored Filters

DTIC Science & Technology

2015-02-01

chromaticity coordinates on the MCC under illuminant C. Measurements were taken with and without filters in front of the colorimeter . Note, for the actual...to measure the chromaticity and luminance values of the different components displayed on the calibrated monitor using a spot colorimeter (Minolta CS...of Illuminant C and the chromaticity values for each of the colored squares were measured using a spot colorimeter (Minolta CS-100). Three

Contingency Awareness Shapes Acquisition and Extinction of Emotional Responses in a Conditioning Model of Pain-Related Fear.

PubMed

Labrenz, Franziska; Icenhour, Adriane; Benson, Sven; Elsenbruch, Sigrid

2015-01-01

As a fundamental learning process, fear conditioning promotes the formation of associations between predictive cues and biologically significant signals. In its application to pain, conditioning may provide important insight into mechanisms underlying pain-related fear, although knowledge especially in interoceptive pain paradigms remains scarce. Furthermore, while the influence of contingency awareness on excitatory learning is subject of ongoing debate, its role in pain-related acquisition is poorly understood and essentially unknown regarding extinction as inhibitory learning. Therefore, we addressed the impact of contingency awareness on learned emotional responses to pain- and safety-predictive cues in a combined dataset of two pain-related conditioning studies. In total, 75 healthy participants underwent differential fear acquisition, during which rectal distensions as interoceptive unconditioned stimuli (US) were repeatedly paired with a predictive visual cue (conditioned stimulus; CS(+)) while another cue (CS(-)) was presented unpaired. During extinction, both CS were presented without US. CS valence, indicating learned emotional responses, and CS-US contingencies were assessed on visual analog scales (VAS). Based on an integrative measure of contingency accuracy, a median-split was performed to compare groups with low vs. high contingency accuracy regarding learned emotional responses. To investigate predictive value of contingency accuracy, regression analyses were conducted. Highly accurate individuals revealed more pronounced negative emotional responses to CS(+) and increased positive responses to CS(-) when compared to participants with low contingency accuracy. Following extinction, highly accurate individuals had fully extinguished pain-predictive cue properties, while exhibiting persistent positive emotional responses to safety signals. In contrast, individuals with low accuracy revealed equally positive emotional responses to both, CS(+) and CS(-). Contingency accuracy predicted variance in the formation of positive responses to safety cues while no predictive value was found for danger cues following acquisition and for neither cue following extinction. Our findings underscore specific roles of learned danger and safety in pain-related acquisition and extinction. Contingency accuracy appears to distinctly impact learned emotional responses to safety and danger cues, supporting aversive learning to occur independently from CS-US awareness. The interplay of cognitive and emotional factors in shaping excitatory and inhibitory pain-related learning may contribute to altered pain processing, underscoring its clinical relevance in chronic pain.

Altered white matter in early visual pathways of humans with amblyopia.

PubMed

Allen, Brian; Spiegel, Daniel P; Thompson, Benjamin; Pestilli, Franco; Rokers, Bas

2015-09-01

Amblyopia is a visual disorder caused by poorly coordinated binocular input during development. Little is known about the impact of amblyopia on the white matter within the visual system. We studied the properties of six major visual white-matter pathways in a group of adults with amblyopia (n=10) and matched controls (n=10) using diffusion weighted imaging (DWI) and fiber tractography. While we did not find significant differences in diffusion properties in cortico-cortical pathways, patients with amblyopia exhibited increased mean diffusivity in thalamo-cortical visual pathways. These findings suggest that amblyopia may systematically alter the white matter properties of early visual pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Segregating the significant from the mundane on a moment-to-moment basis via direct and indirect amygdala contributions

PubMed Central

Lim, Seung-Lark; Padmala, Srikanth; Pessoa, Luiz

2009-01-01

If the amygdala is involved in shaping perceptual experience when affectively significant visual items are encountered, responses in this structure should be correlated with both visual cortex responses and behavioral reports. Here, we investigated how affective significance shapes visual perception during an attentional blink paradigm combined with aversive conditioning. Behaviorally, following aversive learning, affectively significant scenes (CS+) were better detected than neutral (CS−) ones. In terms of mean brain responses, both amygdala and visual cortical responses were stronger during CS+ relative to CS− trials. Increased brain responses in these regions were associated with improved behavioral performance across participants and followed a mediation-like pattern. Importantly, the mediation pattern was observed in a trial-by-trial analysis, revealing that the specific pattern of trial-by-trial variability in brain responses was closely related to single-trial behavioral performance. Furthermore, the influence of the amygdala on visual cortical responses was consistent with a mediation, although partial, via frontal brain regions. Our results thus suggest that affective significance potentially determines the fate of a visual item during competitive interactions by enhancing sensory processing through both direct and indirect paths. In so doing, the amygdala helps separate the significant from the mundane. PMID:19805383

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosoff, B.; Cohn, S.H.; Spencer, H.

The main pathway of Cs/sup 137/ excretion in man following either intravenous or oral administration is via the kidney. The urinary to fecal ratio is approximately 10 : 1. Orally administered Cs/137/ is rapidly and almost completely absorbed. The metabolism of the radioisotope was shown to be similar following either intravenous or oral administration. Cs/sup 137/ disappears very rapidly from plasma and is taken up by red blood cells. The biological half-life of cesium in man deterrained by analyses of excreta of two patients was found to be 50 and 60 days respectively. These values are similar to the biologicalmore » half- lives obtained by long term whole-body counting studies. The distribution of Cs/ sup 137/ in man is fairly uniform in the soft tissues and the concentration decreases with time at different rates. Attempts to enhance the excretion rate of Cs/sup 137/ with diuretics, corticosteroids, and ion exchange resins were unsuccessful. (auth)« less

Calcineurin inhibitors recruit protein kinases JAK2 and JNK, TLR signaling and the UPR to activate NF-κB-mediated inflammatory responses in kidney tubular cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

González-Guerrero, Cristian, E-mail: cristian.gonzalez@fjd.es; Ocaña-Salceda, Carlos, E-mail: carlos.ocana@fjd.es; Berzal, Sergio, E-mail: sberzal@fjd.es

The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are key drugs in current immunosuppressive regimes for solid organ transplantation. However, they are nephrotoxic and promote death and profibrotic responses in tubular cells. Moreover, renal inflammation is observed in CNI nephrotoxicity but the mechanisms are poorly understood. We have now studied molecular pathways leading to inflammation elicited by the CNIs in cultured and kidney tubular cells. Both CsA and tacrolimus elicited a proinflammatory response in tubular cells as evidenced by a transcriptomics approach. Transcriptomics also suggested several potential pathways leading to expression of proinflammatory genes. Validation and functional studies disclosed thatmore » in tubular cells, CNIs activated protein kinases such as the JAK2/STAT3 and TAK1/JNK/AP-1 pathways, TLR4/Myd88/IRAK signaling and the Unfolded Protein Response (UPR) to promote NF-κB activation and proinflammatory gene expression. CNIs also activated an Nrf2/HO-1-dependent compensatory response and the Nrf2 activator sulforaphane inhibited JAK2 and JNK activation and inflammation. A murine model of CsA nephrotoxicity corroborated activation of the proinflammatory pathways identified in cell cultures. Human CNIs nephrotoxicity was also associated with NF-κB, STAT3 and IRE1α activation. In conclusion, CNIs recruit several intracellular pathways leading to previously non-described proinflammatory actions in renal tubular cells. Identification of these pathways provides novel clues for therapeutic intervention to limit CNIs nephrotoxicity. - Highlights: • Molecular mechanisms modulating CNI renal inflammation were investigated. • Kinases, immune receptors and ER stress mediate the inflammatory response to CNIs. • Several intracellular pathways activate NF-κB in CNIs-treated tubular cells. • A NF-κB-dependent cytokine profile characterizes CNIs-induced inflammation. • CNI nephrotoxicity was associated to inflammatory events in mice and human.« less

Audio-visual integration through the parallel visual pathways.

PubMed

Kaposvári, Péter; Csete, Gergő; Bognár, Anna; Csibri, Péter; Tóth, Eszter; Szabó, Nikoletta; Vécsei, László; Sáry, Gyula; Tamás Kincses, Zsigmond

2015-10-22

Audio-visual integration has been shown to be present in a wide range of different conditions, some of which are processed through the dorsal, and others through the ventral visual pathway. Whereas neuroimaging studies have revealed integration-related activity in the brain, there has been no imaging study of the possible role of segregated visual streams in audio-visual integration. We set out to determine how the different visual pathways participate in this communication. We investigated how audio-visual integration can be supported through the dorsal and ventral visual pathways during the double flash illusion. Low-contrast and chromatic isoluminant stimuli were used to drive preferably the dorsal and ventral pathways, respectively. In order to identify the anatomical substrates of the audio-visual interaction in the two conditions, the psychophysical results were correlated with the white matter integrity as measured by diffusion tensor imaging.The psychophysiological data revealed a robust double flash illusion in both conditions. A correlation between the psychophysical results and local fractional anisotropy was found in the occipito-parietal white matter in the low-contrast condition, while a similar correlation was found in the infero-temporal white matter in the chromatic isoluminant condition. Our results indicate that both of the parallel visual pathways may play a role in the audio-visual interaction. Copyright © 2015. Published by Elsevier B.V.

The chlorophyll-deficient golden leaf mutation in cucumber is due to a single nucleotide substitution in CsChlI for magnesium chelatase I subunit.

PubMed

Gao, Meiling; Hu, Liangliang; Li, Yuhong; Weng, Yiqun

2016-10-01

The cucumber chlorophyll-deficient golden leaf mutation is due to a single nucleotide substitution in the CsChlI gene for magnesium chelatase I subunit which plays important roles in the chlorophyll biosynthesis pathway. The Mg-chelatase catalyzes the insertion of Mg(2+) into the protoporphyrin IX in the chlorophyll biosynthesis pathway, which is a protein complex encompassing three subunits CHLI, CHLD, and CHLH. Chlorophyll-deficient mutations in genes encoding the three subunits have played important roles in understanding the structure, function and regulation of this important enzyme. In an EMS mutagenesis population, we identified a chlorophyll-deficient mutant C528 with golden leaf color throughout its development which was viable and able to set fruits and seeds. Segregation analysis in multiple populations indicated that this leaf color mutation was recessively inherited and the green color showed complete dominance over golden color. Map-based cloning identified CsChlI as the candidate gene for this mutation which encoded the CHLI subunit of cucumber Mg-chelatase. The 1757-bp CsChlI gene had three exons and a single nucleotide change (G to A) in its third exon resulted in an amino acid substitution (G269R) and the golden leaf color in C528. This mutation occurred in the highly conserved nucleotide-binding domain of the CHLI protein in which chlorophyll-deficient mutations have been frequently identified. The mutant phenotype, CsChlI expression pattern and the mutated residue in the CHLI protein suggested the mutant allele in C528 is unique among mutations identified so far in different species. This golden leaf mutant not only has its potential in cucumber breeding, but also provides a useful tool in understanding the CHLI function and its regulation in the chlorophyll biosynthesis pathway as well as chloroplast development.

A dual pathways transfer model to account for changes in the radioactive caesium level in demersal and pelagic fish after the Fukushima Daï-ichi nuclear power plant accident

PubMed Central

Bailly-du-Bois, Pascal; Laguionie, Philippe; Morillon, Mehdi; Arnaud, Mireille; Cunin, Pascal

2017-01-01

The Fukushima Daï-ichi nuclear power plant (FDNPP) accident resulted in radioactive Cs being discharged into the local marine environment. While Cs bioaccumulates in biota and slowly depurates, the Cs concentrated in biota constitutes a source of Cs for animals feeding on each other. The marine biota therefore serves as a pool that recycles Cs, and this recycling process delays depuration in the fish feeding on this biota pool. Because the continental shelf is squeezed between the coast and very deep sea, the demersal marine species are confined to a narrow strip along the coast, close to the source of the radioactive input. Unlike demersal species, however, pelagic species are not restricted to the most contaminated area but instead spend some, if not most, of their time and feeding off-shore, far from the input source. We suggest that the feeding pathway for fish is a box whose size depends on their mobility, and that this feeding box is much larger and less contaminated (because of dilution through distance) for pelagic fish than for demersal fish. The aim of this paper is to test this hypothesis and to propose a simple operational model implementing two transfer routes: from seawater and from feeding. The model is then used to match the observational data in the aftermath of the FDNPP accident. PMID:28248982

Comparison of Objective and Subjective Changes Induced by Multiple-Pinhole Glasses and Single-Pinhole Glasses

PubMed Central

2017-01-01

Multiple-pinhole (MPH) glasses are currently sold in many countries with unproven advertisements; however, their objective and subjective effects have not been investigated. Therefore, to investigate the effects of MPH glasses excluding the single-pinhole (SPH) effect, we compared the visual functional changes, reading speed, and ocular discomfort after reading caused by MPH and SPH glasses. Healthy 36 participants with a mean age of 33.1 years underwent examinations of pupil size, visual acuity (VA), depth of focus (DOF), and near point accommodation (NPA); tests for visual field (VF), contrast sensitivity (CS), stereopsis, and reading speed; and a survey of ocular discomfort after reading. Both types of pinhole glasses enlarged pupil diameter and improved VA, DOF, and NPA. However, CS, stereopsis, and VF parameters deteriorated. In comparison with SPH glasses, MPH glasses induced smaller pupil dilation (5.3 and 5.9 mm, P < 0.001) and showed better VF parameters with preserved peripheral VF. However, no significant difference was observed for VA, DOF, NPA, stereopsis, and CS. Reading speed using pinhole glasses was significantly slower than baseline; SPH glasses showed the slowest reading speed. Both types of glasses caused significant ocular discomfort after reading compared with baseline, and symptoms were worst with MPH glasses. In conclusion, both types of pinhole glasses had positive effects due to the pinhole effect; however, they had negative effects on VF, CS, stereopsis, reading speed, and ocular discomfort. In spite of the increased luminance and preserved peripheral VF with MPHs, these glasses caused more severe ocular discomfort than SPH glasses. This clinical trial was registered at www.ClinicalTrials.gov (Identifier: NCT02572544). PMID:28378561

Differential Effects of HRAS Mutation on LTP-Like Activity Induced by Different Protocols of Repetitive Transcranial Magnetic Stimulation.

PubMed

Dileone, Michele; Ranieri, Federico; Florio, Lucia; Capone, Fioravante; Musumeci, Gabriella; Leoni, Chiara; Mordillo-Mateos, Laura; Tartaglia, Marco; Zampino, Giuseppe; Di Lazzaro, Vincenzo

2016-01-01

Costello syndrome (CS) is a rare congenital disorder due to a G12S amino acid substitution in HRAS protoncogene. Previous studies have shown that Paired Associative Stimulation (PAS), a repetitive brain stimulation protocol inducing motor cortex plasticity by coupling peripheral nerve stimulation with brain stimulation, leads to an extremely pronounced motor cortex excitability increase in CS patients. Intermittent Theta Burst Stimulation (iTBS) represents a protocol able to induce motor cortex plasticity by trains of stimuli at 50 Hz. In healthy subjects PAS and iTBS produce similar after-effects in motor cortex excitability. Experimental models showed that HRAS-dependent signalling pathways differently affect LTP induced by different patterns of repetitive synaptic stimulation. We aimed to compare iTBS-induced after-effects on motor cortex excitability with those produced by PAS in CS patients and to observe whether HRAS mutation differentially affects two different forms of neuromodulation protocols. We evaluated in vivo after-effects induced by PAS and iTBS applied over the right motor cortex in 4 CS patients and in 21 healthy age-matched controls. Our findings confirmed HRAS-dependent extremely pronounced PAS-induced after-effects and showed for the first time that iTBS induces no change in MEP amplitude in CS patients whereas both protocols lead to an increase of about 50% in controls. CS patients are characterized by an impairment of iTBS-related LTP-like phenomena besides enhanced PAS-induced after-effects, suggesting that HRAS-dependent signalling pathways have a differential influence on PAS- and iTBS-induced plasticity in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

Goal-Directed Visual Processing Differentially Impacts Human Ventral and Dorsal Visual Representations

PubMed Central

2017-01-01

Recent studies have challenged the ventral/“what” and dorsal/“where” two-visual-processing-pathway view by showing the existence of “what” and “where” information in both pathways. Is the two-pathway distinction still valid? Here, we examined how goal-directed visual information processing may differentially impact visual representations in these two pathways. Using fMRI and multivariate pattern analysis, in three experiments on human participants (57% females), by manipulating whether color or shape was task-relevant and how they were conjoined, we examined shape-based object category decoding in occipitotemporal and parietal regions. We found that object category representations in all the regions examined were influenced by whether or not object shape was task-relevant. This task effect, however, tended to decrease as task-relevant and irrelevant features were more integrated, reflecting the well-known object-based feature encoding. Interestingly, task relevance played a relatively minor role in driving the representational structures of early visual and ventral object regions. They were driven predominantly by variations in object shapes. In contrast, the effect of task was much greater in dorsal than ventral regions, with object category and task relevance both contributing significantly to the representational structures of the dorsal regions. These results showed that, whereas visual representations in the ventral pathway are more invariant and reflect “what an object is,” those in the dorsal pathway are more adaptive and reflect “what we do with it.” Thus, despite the existence of “what” and “where” information in both visual processing pathways, the two pathways may still differ fundamentally in their roles in visual information representation. SIGNIFICANCE STATEMENT Visual information is thought to be processed in two distinctive pathways: the ventral pathway that processes “what” an object is and the dorsal pathway that processes “where” it is located. This view has been challenged by recent studies revealing the existence of “what” and “where” information in both pathways. Here, we found that goal-directed visual information processing differentially modulates shape-based object category representations in the two pathways. Whereas ventral representations are more invariant to the demand of the task, reflecting what an object is, dorsal representations are more adaptive, reflecting what we do with the object. Thus, despite the existence of “what” and “where” information in both pathways, visual representations may still differ fundamentally in the two pathways. PMID:28821655

Copper-Catalyzed Oxidative Reaction of β-Keto Sulfones with Alcohols via C-S Bond Cleavage: Reaction Development and Mechanism Study.

PubMed

Du, Bingnan; Wang, Wenmin; Wang, Yang; Qi, Zhenghang; Tian, Jiaqi; Zhou, Jie; Wang, Xiaochen; Han, Jianlin; Ma, Jing; Pan, Yi

2018-02-16

A Cu-catalyzed cascade oxidative radical process of β-keto sulfones with alcohols has been achieved by using oxygen as an oxidant. In this reaction, β-keto sulfones were converted into sulfinate esters under the oxidative conditions via cleavage of C-S bond. Experimental and computational studies demonstrate that a new pathway is involved in this reaction, which proceeds through the formation of the key four-coordinated Cu II intermediate, O-O bond homolysis induced C-S bond cleavage and Cu-catalyzed esterification to form the final products. This reaction provides a new strategy to sulfonate esters and enriches the research content of C-S bond cleavage and transformations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats.

PubMed

Cardinal, Rudolf N; Parkinson, John A; Lachenal, Guillaume; Halkerston, Katherine M; Rudarakanchana, Nung; Hall, Jeremy; Morrison, Caroline H; Howes, Simon R; Robbins, Trevor W; Everitt, Barry J

2002-08-01

The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an unpaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS+ significantly less often than controls, failing to discriminate between the CS+ and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, Zachary A.; Drager, Andreas; Ebrahim, Ali

Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)—in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics).more » Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools.« less

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

PubMed Central

King, Zachary A.; Dräger, Andreas; Ebrahim, Ali; Sonnenschein, Nikolaus; Lewis, Nathan E.; Palsson, Bernhard O.

2015-01-01

Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)—in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics). Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools. PMID:26313928

Escher: A Web Application for Building, Sharing, and Embedding Data-Rich Visualizations of Biological Pathways

DOE PAGES

King, Zachary A.; Drager, Andreas; Ebrahim, Ali; ...

2015-08-27

Escher is a web application for visualizing data on biological pathways. Three key features make Escher a uniquely effective tool for pathway visualization. First, users can rapidly design new pathway maps. Escher provides pathway suggestions based on user data and genome-scale models, so users can draw pathways in a semi-automated way. Second, users can visualize data related to genes or proteins on the associated reactions and pathways, using rules that define which enzymes catalyze each reaction. Thus, users can identify trends in common genomic data types (e.g. RNA-Seq, proteomics, ChIP)—in conjunction with metabolite- and reaction-oriented data types (e.g. metabolomics, fluxomics).more » Third, Escher harnesses the strengths of web technologies (SVG, D3, developer tools) so that visualizations can be rapidly adapted, extended, shared, and embedded. This paper provides examples of each of these features and explains how the development approach used for Escher can be used to guide the development of future visualization tools.« less

Comparison of radiocesium concentration changes in leguminous and non-leguminous herbaceous plants observed after the Fukushima Dai-ichi Nuclear Power Plant accident.

PubMed

Uchida, Shigeo; Tagami, Keiko

2018-06-01

Transfer of radiocesium from soil to crops is an important pathway for human intake. In the period from one to two years after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, food monitoring results showed that radiocesium concentrations in soybean (a legume) were higher than those in other annual agricultural crops; in these crops, root uptake is the major pathway of radiocesium from soil to plant. However, it was not clear whether or not leguminous and non-leguminous herbaceous plants have different Cs uptake abilities from the same soil because crop sample collection fields were different. In this study, therefore, we compared the concentrations of 137 Cs in seven herbaceous plant species including two leguminous plants (Trifolium pratense L. and Vicia sativa L.) collected in 2012-2016 from the same sampling field in Chiba, Japan that had been affected by the FDNPP accident fallout. Among these species, Petasites japonicus (Siebold & Zucc.) Maxim. showed the highest 137 Cs concentration in 2012-2016. The correlation factor between all concentration data for 137 Cs and those for 40 K in these seven plants was R = 0.54 (p < 0.001) by t-test, thus potassium uptake ability by species would affect radiocesium uptake; however, for each species, no correlation between 137 Cs and 40 K was found. Interestingly, 40 K concentrations in T. pratense, V. sativa and Poaceae family plants did not differ significantly, but 137 Cs data in the Poaceae family plants were significantly lower than those in T. pratense (p < 0.001) and V. sativa (p = 0.017). The results indicated that leguminous species would have higher 137 Cs uptake ability than Poaceae family plants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predicting individual contrast sensitivity functions from acuity and letter contrast sensitivity measurements

PubMed Central

Thurman, Steven M.; Davey, Pinakin Gunvant; McCray, Kaydee Lynn; Paronian, Violeta; Seitz, Aaron R.

2016-01-01

Contrast sensitivity (CS) is widely used as a measure of visual function in both basic research and clinical evaluation. There is conflicting evidence on the extent to which measuring the full contrast sensitivity function (CSF) offers more functionally relevant information than a single measurement from an optotype CS test, such as the Pelli–Robson chart. Here we examine the relationship between functional CSF parameters and other measures of visual function, and establish a framework for predicting individual CSFs with effectively a zero-parameter model that shifts a standard-shaped template CSF horizontally and vertically according to independent measurements of high contrast acuity and letter CS, respectively. This method was evaluated for three different CSF tests: a chart test (CSV-1000), a computerized sine-wave test (M&S Sine Test), and a recently developed adaptive test (quick CSF). Subjects were 43 individuals with healthy vision or impairment too mild to be considered low vision (acuity range of −0.3 to 0.34 logMAR). While each test demands a slightly different normative template, results show that individual subject CSFs can be predicted with roughly the same precision as test–retest repeatability, confirming that individuals predominantly differ in terms of peak CS and peak spatial frequency. In fact, these parameters were sufficiently related to empirical measurements of acuity and letter CS to permit accurate estimation of the entire CSF of any individual with a deterministic model (zero free parameters). These results demonstrate that in many cases, measuring the full CSF may provide little additional information beyond letter acuity and contrast sensitivity. PMID:28006065

The Effect of Simulated Altitude on the Visual Fields of Glaucoma Patients and the Elderly

DTIC Science & Technology

1991-01-01

certification policy does not appear to put pilots or passengers with glaucoma at risk for disease progression. Under short-term exposure to mild hypoxia, we...9. Kobrick JL, Crohn E, Shukitt B, Houston CS, Sutton JR, Cymerman A. Operation Everest II: lack of an effect of extreme altitude on visual contrast

Programming Education with a Blocks-Based Visual Language for Mobile Application Development

ERIC Educational Resources Information Center

Mihci, Can; Ozdener, Nesrin

2014-01-01

The aim of this study is to assess the impact upon academic success of the use of a reference block-based visual programming tool, namely the MIT App Inventor for Android, as an educational instrument for teaching object-oriented GUI-application development (CS2) concepts to students; who have previously completed a fundamental programming course…

Xtalk: a path-based approach for identifying crosstalk between signaling pathways

PubMed Central

Tegge, Allison N.; Sharp, Nicholas; Murali, T. M.

2016-01-01

Motivation: Cells communicate with their environment via signal transduction pathways. On occasion, the activation of one pathway can produce an effect downstream of another pathway, a phenomenon known as crosstalk. Existing computational methods to discover such pathway pairs rely on simple overlap statistics. Results: We present Xtalk, a path-based approach for identifying pairs of pathways that may crosstalk. Xtalk computes the statistical significance of the average length of multiple short paths that connect receptors in one pathway to the transcription factors in another. By design, Xtalk reports the precise interactions and mechanisms that support the identified crosstalk. We applied Xtalk to signaling pathways in the KEGG and NCI-PID databases. We manually curated a gold standard set of 132 crosstalking pathway pairs and a set of 140 pairs that did not crosstalk, for which Xtalk achieved an area under the receiver operator characteristic curve of 0.65, a 12% improvement over the closest competing approach. The area under the receiver operator characteristic curve varied with the pathway, suggesting that crosstalk should be evaluated on a pathway-by-pathway level. We also analyzed an extended set of 658 pathway pairs in KEGG and to a set of more than 7000 pathway pairs in NCI-PID. For the top-ranking pairs, we found substantial support in the literature (81% for KEGG and 78% for NCI-PID). We provide examples of networks computed by Xtalk that accurately recovered known mechanisms of crosstalk. Availability and implementation: The XTALK software is available at http://bioinformatics.cs.vt.edu/~murali/software. Crosstalk networks are available at http://graphspace.org/graphs?tags=2015-bioinformatics-xtalk. Contact: ategge@vt.edu, murali@cs.vt.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26400040

Pedunculopontine tegmental nucleus lesions impair stimulus--reward learning in autoshaping and conditioned reinforcement paradigms.

PubMed

Inglis, W L; Olmstead, M C; Robbins, T W

2000-04-01

The role of the pedunculopontine tegmental nucleus (PPTg) in stimulus-reward learning was assessed by testing the effects of PPTg lesions on performance in visual autoshaping and conditioned reinforcement (CRf) paradigms. Rats with PPTg lesions were unable to learn an association between a conditioned stimulus (CS) and a primary reward in either paradigm. In the autoshaping experiment, PPTg-lesioned rats approached the CS+ and CS- with equal frequency, and the latencies to respond to the two stimuli did not differ. PPTg lesions also disrupted discriminated approaches to an appetitive CS in the CRf paradigm and completely abolished the acquisition of responding with CRf. These data are discussed in the context of a possible cognitive function of the PPTg, particularly in terms of lesion-induced disruptions of attentional processes that are mediated by the thalamus.

Validation of an instrument to assess visual ability in children with visual impairment in China.

PubMed

Huang, Jinhai; Khadka, Jyoti; Gao, Rongrong; Zhang, Sifang; Dong, Wenpeng; Bao, Fangjun; Chen, Haisi; Wang, Qinmei; Chen, Hao; Pesudovs, Konrad

2017-04-01

To validate a visual ability instrument for school-aged children with visual impairment in China by translating, culturally adopting and Rasch scaling the Cardiff Visual Ability Questionnaire for Children (CVAQC). The 25-item CVAQC was translated into Mandarin using a standard protocol. The translated version (CVAQC-CN) was subjected to cognitive testing to ensure a proper cultural adaptation of its content. Then, the CVAQC-CN was interviewer-administered to 114 school-aged children and young people with visual impairment. Rasch analysis was carried out to assess its psychometric properties. The correlation between the CVAQC-CN visual ability scores and clinical measure of vision (visual acuity; VA and contrast sensitivity, CS) were assessed using Spearman's r. Based on cultural adaptation exercise, cognitive testing, missing data and Rasch metrics-based iterative item removal, three items were removed from the original 25. The 22-item CVAQC-CN demonstrated excellent measurement precision (person separation index, 3.08), content validity (item separation, 10.09) and item reliability (0.99). Moreover, the CVAQC-CN was unidimensional and had no item bias. The person-item map indicated good targeting of item difficulty to person ability. The CVAQC-CN had moderate correlations between CS (-0.53, p<0.00001) and VA (0.726, p<0.00001), respectively, indicating its validity. The 22-item CVAQC-CN is a psychometrically robust and valid instrument to measure visual ability in children with visual impairment in China. The instrument can be used as a clinical and research outcome measure to assess the change in visual ability after low vision rehabilitation intervention. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Mechanism of permeability-enhancing effect of EDTA and boric acid on the corneal penetration of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl] methylimidazole-5-carboxylic acid monohydrate (CS-088).

PubMed

Kikuchi, Takayuki; Suzuki, Masahiko; Kusai, Akira; Iseki, Ken; Sasaki, Hitoshi; Nakashima, Kenichiro

2005-08-11

This study was conducted to clarify the penetration properties of 4-[1-hydroxy-1-methylethyl]-2-propyl-1-[4-[2-[tetrazole-5-yl]phenyl]phenyl]methylimidazole-5-carboxylic acid monohydrate (CS-088), an ophthalmic agent, and the mechanism of the permeability-enhancing effect of EDTA and boric acid (EDTA/boric acid) on the corneal penetration of CS-088. In the absence of additives, corneal permeability decreased with increasing concentration of CS-088 as CS-088 monomers self-associate to form dimers. Presence of EDTA/boric acid caused no significant changes in the physicochemical properties of CS-088, the apparent partition coefficient or the mean particle size of CS-088. EDTA/boric acid induced only a slight change in the zeta potential of liposomes used as a model of the biological membrane. On the other hand, EDTA/boric acid significantly increased membrane fluidity of liposomes, whereas other buffering agents tested did not. This effect was synergistic and concentration-dependent for both EDTA and boric acid as was observed in in vitro corneal penetration of CS-088. In accordance with the result, the rate of CS-088 permeation into the liposomes significantly increased by the addition of EDTA/boric acid. Therefore, it was demonstrated that EDTA/boric acid promotes corneal penetration of CS-088 through the transcellular pathway by increasing membrane fluidity. Conversely, other buffering agents decreased corneal permeability of CS-088 by inducing further self-association of CS-088 aggregates.

[Cynomorium songaricum improves sperm count and motility and serum testosterone level and promotes proliferation of undifferentiated spermatogonia in oligoasthenospermia rats].

PubMed

Cao, Yi-Juan; Li, Zhen-Bei; Qi, Yu-Juan; Liu, Ying; Gu, Juan; Hu, Fang-Fang; Zhang, Wen-da; Hao, Lin; Hou, Jian-Quan; Han, Cong-Hui

2016-12-01

To investigate the effects of cynomorium songaricum (CS) decoction on the testis weight, serum testosterone level, and sperm parameters of rats with oligoasthenospermia (OAS), explore its action mechanism of improving the proliferation of undifferentiated spermatogonial cells, and provide some experimental and theoretical evidence for the development of new Chinese drugs for OAS. Thirty 8-week-old male SD rats were randomly divided into five groups of equal number: blank control, model control, high-dose CS, medium-dose CS, and low-dose CS. OAS models were established by intraperitoneal injection of cyclophosphamide and, a month later, treated intragastrically with normal saline or CS at 2, 1, and 0.5 g per kg of the body weight per day, all for 4 weeks. Then, the testes of the animals were harvested to obtain the testicular weight, sperm concentration and motility, and the level of serum testosterone (T), detect the expressions of the transcription factor 1 (Oct4), Thy-1 cell surface antigen (Thy1), promyelocytic leukemia zinc finger (PLZF), KIT proto-oncogene receptor tyrosine kinase (C-kit) and glial cell-derived neurotrophic factor (GDNF) in the testis tissue of the rats in the low-dose CS group by real-time PCR. The testis weights in the blank control, model control, high-dose CS, medium-dose CS, and low-dose CS groups were (1.52±0.06), (1.55±0.06), (1.43±0.30), (1.35±0.40) and (1.34±0.04) g, respectively, not significantly different in the blank and model controls from those in the CS groups (P>0.05). The visual field sperm count per 10 HP was significantly increased in the high-, medium-, and low-dose CS groups (202±20, 196±5 and 216±25) as compared with the blank and model controls (200±15 and 134±30) (P<0.05). The mRNA expressions of the Oct4, Thy1, PLZF and GDNF genes were remarkably higher in the low-dose CS group than in the controls (P<0.05), but that of the C-kit gene showed no significant difference from the latter (P>0.05). The visual field sperm motility per 10 HP was markedly increased in the blank control (［52.1±5.5］%), model control (［38.1±2.5］%), high-dose CS (［59.1±9.5］%), medium-dose CS (［58.7±9.5］%), and low-dose CS (［49.6±1.0］%) groups, and so was the level of serum testosterone (［190±87.5］, ［82.5±25.8］, ［229±75.6］, ［331±86.7］ and ［185±82.4］ mmol/L), both remarkably higher in the CS groups than in the model controls (P<0.05) but with no statistically significant difference between the CS groups and the blank controls (P>0.05). CS can significantly improve sperm concentration, sperm motility and serum T level in OAS rats, probably by inducing the expression of GDNF in the rat Sertoli cells, promoting the proliferation of undifferentiated spermatogonial cells, and enhancing spermatogenesis.

Site-specific identification of heparan and chondroitin sulfate glycosaminoglycans in hybrid proteoglycans.

PubMed

Noborn, Fredrik; Gomez Toledo, Alejandro; Green, Anders; Nasir, Waqas; Sihlbom, Carina; Nilsson, Jonas; Larson, Göran

2016-10-03

Heparan sulfate (HS) and chondroitin sulfate (CS) are complex polysaccharides that regulate important biological pathways in virtually all metazoan organisms. The polysaccharides often display opposite effects on cell functions with HS and CS structural motifs presenting unique binding sites for specific ligands. Still, the mechanisms by which glycan biosynthesis generates complex HS and CS polysaccharides required for the regulation of mammalian physiology remain elusive. Here we present a glycoproteomic approach that identifies and differentiates between HS and CS attachment sites and provides identity to the core proteins. Glycopeptides were prepared from perlecan, a complex proteoglycan known to be substituted with both HS and CS chains, further digested with heparinase or chondroitinase ABC to reduce the HS and CS chain lengths respectively, and thereafter analyzed by nLC-MS/MS. This protocol enabled the identification of three consensus HS sites and one hybrid site, carrying either a HS or a CS chain. Inspection of the amino acid sequence at the hybrid attachment locus indicates that certain peptide motifs may encode for the chain type selection process. This analytical approach will become useful when addressing fundamental questions in basic biology specifically in elucidating the functional roles of site-specific glycosylations of proteoglycans.

Folate-Chitosan Nanoparticles Loaded with Ursolic Acid Confer Anti-Breast Cancer Activities in vitro and in vivo

NASA Astrophysics Data System (ADS)

Jin, Hua; Pi, Jiang; Yang, Fen; Jiang, Jinhuan; Wang, Xiaoping; Bai, Haihua; Shao, Mingtao; Huang, Lei; Zhu, Haiyan; Yang, Peihui; Li, Lihua; Li, Ting; Cai, Jiye; Chen, Zheng W.

2016-07-01

Ursolic acid (UA) has proved to have broad-spectrum anti-tumor effects, but its poor water solubility and incompetent targeting property largely limit its clinical application and efficiency. Here, we synthesized a nanoparticle-based drug carrier composed of chitosan, UA and folate (FA-CS-UA-NPs) and demonstrated that FA-CS-UA-NPs could effectively diminish off-target effects and increase local drug concentrations of UA. Using MCF-7 cells as in vitro model for anti-cancer mechanistic studies, we found that FA-CS-UA-NPs could be easily internalized by cancer cells through a folate receptor-mediated endocytic pathway. FA-CS-UA-NPs entered into lysosome, destructed the permeability of lysosomal membrane, and then got released from lysosomes. Subsequently, FA-CS-UA-NPs localized into mitochondria but not nuclei. The prolonged retention of FA-CS-UA-NPs in mitochondria induced overproduction of ROS and destruction of mitochondrial membrane potential, and resulted in the irreversible apoptosis in cancer cells. In vivo experiments showed that FA-CS-UA-NPs could significantly reduce breast cancer burden in MCF-7 xenograft mouse model. These results suggested that FA-CS-UA-NPs could further be explored as an anti-cancer drug candidate and that our approach might provide a platform to develop novel anti-cancer drug delivery system.

Fear acquisition and extinction in offspring of mothers with anxiety and depressive disorders.

PubMed

Waters, Allison M; Peters, Rosie-Mae; Forrest, Kylee E; Zimmer-Gembeck, Melanie

2014-01-01

Maternal anxiety and depression are significant risk factors for the development of these disorders in offspring. The pathways through which risk is conferred remain unclear. This study examined fear acquisition and extinction in 26 children at high risk for emotional disorders by virtue of maternal psychopathology (n=14 with a mother with a principal anxiety disorder and n=12 with a mother with a principal unipolar depressive disorder) and 31 low risk controls using a discriminative Pavlovian conditioning procedure. Participants, aged between 7 and 14 years, completed 16 trials of discriminative conditioning of two geometric figures, with (CS+) and without (CS-) an aversive tone (US), followed by 8 extinction trials (4×CS+, 4×CS-). In the context of comparable discriminative conditioning, children of anxious mothers showed larger skin conductance responses during extinction to the CS+ compared to the CS-, and to both CSs from the first to the second block of extinction trials, in comparison with low risk controls. Compared to low risk controls, children of depressed mothers showed smaller skin conductance responses to the CS+ than the CS- during acquisition. These findings suggest distinct psychophysiological premorbid risk markers in offspring of anxious and depressed mothers. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Observed Eastward Progression of the Fukushima 134Cs Signal Across the North Pacific

NASA Astrophysics Data System (ADS)

Yoshida, S.; Macdonald, A. M.; Jayne, S. R.; Rypina, I.; Buesseler, K.

2015-12-01

Radionuclide samples taken as part of hydrographic surveys at 30°N in the North Pacific reveal that the easternmost edge of Fukushima-derived 134Cs observed at 174.3°W in 2012 had progressed eastward across the basin to 160.6°W by 2013. The 2013 30°N observations indicate surface 134Cs concentrations of 3-5 Bq/m3 between 160°E and 160°W, slightly lower concentrations west of 160°E and no detectable signal east of 160.6°W. Profile samples show 134Cs penetration to 500 m west of 180° with shoaling penetration depth toward to the east. The near-uniform vertical distribution of 137Cs between 152°W and 121.3°W in the top 500 m is indicative of trace amounts of radionuclides remaining from weapons testing. The physical processes responsible for the deep 134Cs penetration in the western Pacific appear to be related to distinct water mass subduction pathways, however the timing and rapidity of deep penetration over the broad scales observed has yet to be clarified.

Inhibition of the mesoamygdala dopaminergic pathway impairs the retrieval of conditioned fear associations.

PubMed

Nader, K; LeDoux, J E

1999-10-01

Previous findings have demonstrated that systemic dopaminergic manipulations impair the retrieval of Pavlovian conditioned fear. A second-order fear-conditioning paradigm was used to test whether the dopaminergic projection from the ventral tegmental area (VTA) to the lateral and basal amygdala (LBA) can affect conditioned fear. Phase 1 entailed conditioned stimulus-unconditioned stimulus (CS1-US) pairings. In Phase 2, drugs were infused in either the LBA or VTA prior to pairings of CS2 (a second cue) with CS1. In Phase 3, freezing behavior elicited by CS2 was tested without drugs. Infusions of the D2 agonist quinpirole into the VTA or of the D1 antagonist SCH 23390 into the LBA caused a decrease in freezing to CS2. Both manipulations decrease D1 receptor activation in the LBA. Infusions of the D1 agonist SKF 38393 into the LBA had no effect. This pattern of results is consistent with the hypothesis that the VTA-LBA dopaminergic projection modulates the retrieval of an association between a CS and footshock US.

Incorporation of additional radionuclides and the external exposure pathway into the BECAMP (Basic Environmental Compliance and Monitoring Program) radiological assessment model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, Yook C.; Rodean, H.C.; Anspaugh, L.R.

The Nevada Applied Ecology Group (NAEG) Model of transport and dose for transuranic radionuclides was modified and expanded for the analysis of radionuclides other than pure alpha-emitters. Doses from internal and external exposures were estimated for the inventories and soil distributions of the individual radionuclides quantified in Areas 2 and 4 of the Nevada Test Site (NTS). We found that the dose equivalents via inhalation to liver, lungs, bone marrow, and bone surface from the plutonium isotopes and /sup 241/Am, those via ingestion to bone marrow and bone surfaces from /sup 90/Sr, and those via ingestion to all the targetmore » organs from /sup 137/Cs were the highest from internal exposures. The effective dose equivalents from /sup 137/Cs, /sup 152/Eu, and /sup 154/Eu were the highest from the external exposures. The /sup 60/Co, /sup 152/Eu, /sup 154/Eu, and /sup 155/Eu dose estimates for external exposures greatly exceeded those for internal exposures. The /sup 60/Co, /sup 90/Sr, and /sup 137/Cs dose equivalents from internal exposures were underestimated due to the adoption of some of the foodchain parameter values originally selected for /sup 239/Pu. Nonetheless, the ingestion pathway contributed significantly to the dose estimates for /sup 90/Sr and /sup 137/Cs, but contributed very much less than external exposures to the dose estimates for /sup 60/Co. Therefore, the use of more appropriate values would not alter the identification of important radionuclides, pathways, target organs, and exposure modes in this analysis. 19 refs., 13 figs., 12 tabs.« less

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development.

PubMed

Sears, Catherine R; Zhou, Huaxin; Justice, Matthew J; Fisher, Amanda J; Saliba, Jacob; Lamb, Isaac; Wicker, Jessica; Schweitzer, Kelly S; Petrache, Irina

2018-03-01

Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema.

Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers

PubMed Central

Sereno, José; Nunes, Sara; Rodrigues-Santos, Paulo; Rocha-Pereira, Petronila; Fernandes, João; Teixeira, Frederico; Reis, Flávio

2014-01-01

Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (n = 6) were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-β, NF-κ β, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF-β and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL. PMID:24971338

The Sensory Features of a Food Cue Influence Its Ability to Act as an Incentive Stimulus and Evoke Dopamine Release in the Nucleus Accumbens Core

ERIC Educational Resources Information Center

Singer, Bryan F.; Bryan, Myranda A.; Popov, Pavlo; Scarff, Raymond; Carter, Cody; Wright, Erin; Aragona, Brandon J.; Robinson, Terry E.

2016-01-01

The sensory properties of a reward-paired cue (a conditioned stimulus; CS) may impact the motivational value attributed to the cue, and in turn influence the form of the conditioned response (CR) that develops. A cue with multiple sensory qualities, such as a moving lever-CS, may activate numerous neural pathways that process auditory and visual…

Combined analysis of 1,3-benzodioxoles by crystalline sponge X-ray crystallography and laser desorption ionization mass spectrometry.

PubMed

Hayashi, Yukako; Ohara, Kazuaki; Taki, Rika; Saeki, Tomomi; Yamaguchi, Kentaro

2018-03-12

The crystalline sponge (CS) method, which employs single-crystal X-ray diffraction to determine the structure of an analyte present as a liquid or an oil and having a low melting point, was used in combination with laser desorption ionization mass spectrometry (LDI-MS). 1,3-Benzodioxole derivatives were encapsulated in CS and their structures were determined by combining X-ray crystallography and MS. After the X-ray analysis, the CS was subjected to imaging mass spectrometry (IMS) with an LDI spiral-time-of-flight mass spectrometer (TOF-MS). The ion detection area matched the microscopic image of the encapsulated CS. In addition, the accumulated 1D mass spectra showed that fragmentation of the guest molecule (hereafter, guest) can be easily visualized without any interference from the fragment ions of CS except for two strong ion peaks derived from the tridentate ligand TPT (2,4,6-tris(4-pyridyl)-1,3,5-triazine) of the CS and its fragment. X-ray analysis clearly showed the presence of the guest as well as the π-π, CH-halogen, and CH-O interactions between the guest and the CS framework. However, some guests remained randomly diffused in the nanopores of CS. In addition, the detection limit was less than sub-pmol order based on the weight and density of CS determined by X-ray analysis. Spectroscopic data, such as UV-vis and NMR, also supported the encapsulation of the guest through the interaction between the guest and CS components. The results denote that the CS-LDI-MS method, which combines CS, X-ray analysis and LDI-MS, is effective for structure determination.

Radiocesium distribution in sugi (Cryptomeria japonica) in eastern Japan: translocation from needles to pollen.

PubMed

Kanasashi, Tsutomu; Sugiura, Yuki; Takenaka, Chisato; Hijii, Naoki; Umemura, Mitsutoshi

2015-01-01

We assessed the radiocesium contamination of sugi (Cryptomeria japonica) forests in eastern Japan from November 2012 to February 2013, including 80 sites in Fukushima and 35 sites in other regions (Tohoku and Kanto-Koshinetsu), by measuring the (137)Cs concentrations in needles of different ages, male flowers, and pollen. Over a wide geographic area, needles that were present at the time of the Fukushima Dai-ichi Nuclear Power Plant accident contained much higher (137)Cs concentrations than needles that emerged after the accident. This result, together with visual analysis of (137)Cs distribution using autoradiography, indicated that some of the (137)Cs derived from direct fallout remained on the surface of the older needles. Since we also detected (137)Cs in younger needles and male flowers, we concluded that (137)Cs was translocated toward the tips of sugi needles. The (137)Cs concentration in male flowers was higher than and positively correlated with that in the currently growing (2012) needles. Also, a positive relationship was observed between the (137)Cs concentration of male flowers and pollen, and they were found to be nearly identical (137)Cs concentration. These results indicate the occurrence of acropetal translocation of (137)Cs from old needles to young needles, male flowers and pollen. However, the results as related to (137)Cs concentration in the needles of three different ages differed from the results of similar studies conducted more than 4 y after the Chernobyl accident. This suggests that, 2 y after the Fukushima Dai-ichi NPP accident, the distribution of (137)Cs in the sugi forests has not yet reached a steady state. Copyright © 2014 Elsevier Ltd. All rights reserved.

Abnormal white matter tractography of visual pathways detected by high-angular-resolution diffusion imaging (HARDI) corresponds to visual dysfunction in cortical/cerebral visual impairment

PubMed Central

Bauer, Corinna M.; Heidary, Gena; Koo, Bang-Bon; Killiany, Ronald J.; Bex, Peter; Merabet, Lotfi B.

2014-01-01

Cortical (cerebral) visual impairment (CVI) is characterized by visual dysfunction associated with damage to the optic radiations and/or visual cortex. Typically it results from pre- or perinatal hypoxic damage to postchiasmal visual structures and pathways. The neuroanatomical basis of this condition remains poorly understood, particularly with regard to how the resulting maldevelopment of visual processing pathways relates to observations in the clinical setting. We report our investigation of 2 young adults diagnosed with CVI and visual dysfunction characterized by difficulties related to visually guided attention and visuospatial processing. Using high-angular-resolution diffusion imaging (HARDI), we characterized and compared their individual white matter projections of the extrageniculo-striate visual system with a normal-sighted control. Compared to a sighted control, both CVI cases revealed a striking reduction in association fibers, including the inferior frontal-occipital fasciculus as well as superior and inferior longitudinal fasciculi. This reduction in fibers associated with the major pathways implicated in visual processing may provide a neuroanatomical basis for the visual dysfunctions observed in these patients. PMID:25087644

I'll take the low road: the evolutionary underpinnings of visually triggered fear

PubMed Central

Carr, James A.

2015-01-01

Although there is general agreement that the central nucleus of the amygdala (CeA) is critical for triggering the neuroendocrine response to visual threats, there is uncertainty about the role of subcortical visual pathways in this process. Primates in general appear to depend less on subcortical visual pathways than other mammals. Yet, imaging studies continue to indicate a role for the superior colliculus and pulvinar nucleus in fear activation, despite disconnects in how these brain structures communicate not only with each other but with the amygdala. Studies in fish and amphibians suggest that the neuroendocrine response to visual threats has remained relatively unchanged for hundreds of millions of years, yet there are still significant data gaps with respect to how visual information is relayed to telencephalic areas homologous to the CeA, particularly in fish. In fact ray finned fishes may have evolved an entirely different mechanism for relaying visual information to the telencephalon. In part because they lack a pathway homologous to the lateral geniculate-striate cortex pathway of mammals, amphibians continue to be an excellent model for studying how stress hormones in turn modulate fear activating visual pathways. Glucocorticoids, melanocortin peptides, and CRF all appear to play some role in modulating sensorimotor processing in the optic tectum. These observations, coupled with data showing control of the hypothalamus-pituitary-adrenal axis by the superior colliculus, suggest a fear/stress/anxiety neuroendocrine circuit that begins with first order synapses in subcortical visual pathways. Thus, comparative studies shed light not only on how fear triggering visual pathways came to be, but how hormones released as a result of this activation modulate these pathways. PMID:26578871

Entamoeba mitosomes play an important role in encystation by association with cholesteryl sulfate synthesis

PubMed Central

Mi-ichi, Fumika; Miyamoto, Tomofumi; Takao, Shouko; Jeelani, Ghulam; Hashimoto, Tetsuo; Hara, Hiromitsu; Nozaki, Tomoyoshi; Yoshida, Hiroki

2015-01-01

Hydrogenosomes and mitosomes are mitochondrion-related organelles (MROs) that have highly reduced and divergent functions in anaerobic/microaerophilic eukaryotes. Entamoeba histolytica, a microaerophilic, parasitic amoebozoan species, which causes intestinal and extraintestinal amoebiasis in humans, possesses mitosomes, the existence and biological functions of which have been a longstanding enigma in the evolution of mitochondria. We previously demonstrated that sulfate activation, which is not generally compartmentalized to mitochondria, is a major function of E. histolytica mitosomes. However, because the final metabolites of sulfate activation remain unknown, the overall scheme of this metabolism and the role of mitosomes in Entamoeba have not been elucidated. In this study we purified and identified cholesteryl sulfate (CS) as a final metabolite of sulfate activation. We then identified the gene encoding the cholesteryl sulfotransferase responsible for synthesizing CS. Addition of CS to culture media increased the number of cysts, the dormant form that differentiates from proliferative trophozoites. Conversely, chlorate, a selective inhibitor of the first enzyme in the sulfate-activation pathway, inhibited cyst formation in a dose-dependent manner. These results indicate that CS plays an important role in differentiation, an essential process for the transmission of Entamoeba between hosts. Furthermore, we show that Mastigamoeba balamuthi, an anaerobic, free-living amoebozoan species, which is a close relative of E. histolytica, also has the sulfate-activation pathway in MROs but does not possess the capacity for CS production. Hence, we propose that a unique function of MROs in Entamoeba contributes to its adaptation to its parasitic life cycle. PMID:25986376

Cigarette smoke-induced alveolar epithelial-mesenchymal transition is mediated by Rac1 activation.

PubMed

Shen, Hui-juan; Sun, Yan-hong; Zhang, Shui-juan; Jiang, Jun-xia; Dong, Xin-wei; Jia, Yong-liang; Shen, Jian; Guan, Yan; Zhang, Lin-hui; Li, Fen-fen; Lin, Xi-xi; Wu, Xi-mei; Xie, Qiang-min; Yan, Xiao-feng

2014-06-01

Epithelial-mesenchymal transition (EMT) is the major pathophysiological process in lung fibrosis observed in chronic obstructive pulmonary disease (COPD) and lung cancer. Smoking is a risk factor for developing EMT, yet the mechanism remains largely unknown. In this study, we investigated the role of Rac1 in cigarette smoke (CS) induced EMT. EMT was induced in mice and pulmonary epithelial cells by exposure of CS and cigarette smoke extract (CSE) respectively. Treatment of pulmonary epithelial cells with CSE elevated Rac1 expression associated with increased TGF-β1 release. Blocking TGF-β pathway restrained CSE-induced changes in EMT-related markers. Pharmacological inhibition or knockdown of Rac1 decreased the CSE exposure induced TGF-β1 release and ameliorated CSE-induced EMT. In CS-exposed mice, pharmacological inhibition of Rac1 reduced TGF-β1 release and prevented aberrations in expression of EMT markers, suggesting that Rac1 is a critical signaling molecule for induction of CS-stimulated EMT. Furthermore, Rac1 inhibition or knockdown abrogated CSE-induced Smad2 and Akt (PKB, protein kinase B) activation in pulmonary epithelial cells. Inhibition of Smad2, PI3K (phosphatidylinositol 3-kinase) or Akt suppressed CSE-induced changes in epithelial and mesenchymal marker expression. Altogether, these data suggest that CS initiates EMT through Rac1/Smad2 and Rac1/PI3K/Akt signaling pathway. Our data provide new insights into the fundamental basis of EMT and suggest a possible new course of therapy for COPD and lung cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

A unified model for the molecular basis of Xeroderma pigmentosum-Cockayne Syndrome

PubMed Central

Moriel-Carretero, María; Herrera-Moyano, Emilia; Aguilera, Andrés

2015-01-01

Nucleotide Excision Repair (NER) is a pathway that removes lesions distorting the DNA helix. The molecular basis of the rare diseases Xeroderma pigmentosum (XP) and Cockayne Syndrome (CS) are explained based on the defects happening in 2 NER branches: Global-Genome Repair and Transcription-Coupled Repair, respectively. Nevertheless, both afflictions sporadically occur together, giving rise to XP/CS; however, the molecular basis of XP/CS is not understood very well. Many efforts have been made to clarify why mutations in only 4 NER genes, namely XPB, XPD, XPF and XPG, are the basis of this disease. Effort has also been made to unravel why mutations within these genes lead to XP, XP/CS, or other pathologies. We have recently contributed to the disclosure of this puzzle by characterizing Rad3/XPD mutations in Saccharomyces cerevisiae and human cells. Based on our, and others', observations, we propose a model compatible with all XP/CS cases and the current bibliography. PMID:26460500

Central localization of plasticity involved in appetitive conditioning in Lymnaea

PubMed Central

Straub, Volko A.; Styles, Benjamin J.; Ireland, Julie S.; O'Shea, Michael; Benjamin, Paul R.

2004-01-01

Learning to associate a conditioned (CS) and unconditioned stimulus (US) results in changes in the processing of CS information. Here, we address directly the question whether chemical appetitive conditioning of Lymnaea feeding behavior involves changes in the peripheral and/or central processing of the CS by using extracellular recording techniques to monitor neuronal activity at two stages of the sensory processing pathway. Our data show that appetitive conditioning does not affect significantly the overall CS response of afferent nerves connecting chemosensory structures in the lips and tentacles to the central nervous system (CNS). In contrast, neuronal output from the cerebral ganglia, which represent the first central processing stage for chemosensory information, is enhanced significantly in response to the CS after appetitive conditioning. This demonstrates that chemical appetitive conditioning in Lymnaea affects the central, but not the peripheral processing of chemosensory information. It also identifies the cerebral ganglia of Lymnaea as an important site for neuronal plasticity and forms the basis for detailed cellular studies of neuronal plasticity. PMID:15537733

Sensorimotor Integration by Corticospinal System

PubMed Central

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior. PMID:27013985

Sensorimotor Integration by Corticospinal System.

PubMed

Moreno-López, Yunuen; Olivares-Moreno, Rafael; Cordero-Erausquin, Matilde; Rojas-Piloni, Gerardo

2016-01-01

The corticospinal (CS) tract is a complex system which targets several areas of the spinal cord. In particular, the CS descending projection plays a major role in motor command, which results from direct and indirect control of spinal cord pre-motor interneurons as well as motoneurons. But in addition, this system is also involved in a selective and complex modulation of sensory feedback. Despite recent evidence confirms that CS projections drive distinct segmental neural circuits that are part of the sensory and pre-motor pathways, little is known about the spinal networks engaged by the corticospinal tract (CST), the organization of CS projections, the intracortical microcircuitry, and the synaptic interactions in the sensorimotor cortex (SMC) that may encode different cortical outputs to the spinal cord. Here is stressed the importance of integrated approaches for the study of sensorimotor function of CS system, in order to understand the functional compartmentalization and hierarchical organization of layer 5 output neurons, who are key elements for motor control and hence, of behavior.

Parallel cascade selection molecular dynamics for efficient conformational sampling and free energy calculation of proteins

NASA Astrophysics Data System (ADS)

Kitao, Akio; Harada, Ryuhei; Nishihara, Yasutaka; Tran, Duy Phuoc

2016-12-01

Parallel Cascade Selection Molecular Dynamics (PaCS-MD) was proposed as an efficient conformational sampling method to investigate conformational transition pathway of proteins. In PaCS-MD, cycles of (i) selection of initial structures for multiple independent MD simulations and (ii) conformational sampling by independent MD simulations are repeated until the convergence of the sampling. The selection is conducted so that protein conformation gradually approaches a target. The selection of snapshots is a key to enhance conformational changes by increasing the probability of rare event occurrence. Since the procedure of PaCS-MD is simple, no modification of MD programs is required; the selections of initial structures and the restart of the next cycle in the MD simulations can be handled with relatively simple scripts with straightforward implementation. Trajectories generated by PaCS-MD were further analyzed by the Markov state model (MSM), which enables calculation of free energy landscape. The combination of PaCS-MD and MSM is reported in this work.

Human Neural Cells Transiently Express Reelin during Olfactory Placode Development

PubMed Central

Antal, M. Cristina; Samama, Brigitte; Ghandour, M. Said; Boehm, Nelly

2015-01-01

Reelin, an extracellular glycoprotein is essential for migration and correct positioning of neurons during development. Since the olfactory system is known as a source of various migrating neuronal cells, we studied Reelin expression in the two chemosensory olfactory systems, main and accessory, during early developmental stages of human foetuses/embryos from Carnegie Stage (CS) 15 to gestational week (GW) 14. From CS 15 to CS 18, but not at later stages, a transient expression of Reelin was detected first in the presumptive olfactory and then in the presumptive vomeronasal epithelium. During the same period, Reelin-positive cells detach from the olfactory/vomeronasal epithelium and migrate through the mesenchyme beneath the telencephalon. Dab 1, an adaptor protein of the Reelin pathway, was simultaneously expressed in the migratory mass from CS16 to CS17 and, at later stages, in the presumptive olfactory ensheathing cells. Possible involvements of Reelin and Dab 1 in the peripheral migrating stream are discussed. PMID:26270645

Summary of the BIOMOVS A4 scenario: Testing models of the air-pasture-cow milk pathway using Chernobyl fallout data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, S.R.; Hoffman, F.O.; Koehler, H.

1996-08-01

A unique opportunity to test dose assessment models arose after the Chernobyl reactor accident. During the passage of the contaminated plume, concentrations of {sup 131}I and {sup 137}Cs in air, pasture, and cow`s milk were collected at various sites in the northern hemisphere. Afterwards, contaminated pasture and milk samples were analyzed over time. Under the auspices of the Biospheric Model Validation Study (BIOMOVS), data from 13 sites for {sup 131}I and 10 sites for {sup 137}Cs were used to test model predictions for the air-pasture-cow milk pathway. Calculations were submitted for 23 models, 10 of which were quasi-steady state. Themore » others were time-dependent. Daily predictions and predictions of time-integrated concentration of {sup 131}I and {sup 137}Cs in pasture grass and milk for six months post-accident were calculated and compared with observed data. Testing against data from several locations over time for several steps in the air-to-milk pathway resulted in a better understanding of important processes and how they should be modeled. This model testing exercise showed both the strengths and weaknesses of the models and revealed the importance of testing all parts of dose assessment models whenever possible. 19 refs., 14 figs., 4 tabs.« less

Delayed Luminance and Chromatic Contrast Sensitivity in Infants with Spontaneously Regressed Retinopathy of Prematurity

PubMed Central

Bosworth, Rain; Robbins, Shira L.; Granet, David B.; Dobkins, Karen

2013-01-01

Background The current study assessed whether contrast sensitivity is affected in preterm infants with a history of spontaneously regressed retinopathy of prematurity (ROP, Stages 1–3). Specifically, we employed luminance (light/dark) and chromatic (red/green) stimuli, which are mediated by the magnocellular (M) and parvocellular (P) subcortical pathways, respectively. Methods Contrast sensitivity (CS) was measured using forced choice preferential looking testing in 21 infants with a history of ROP and 41 control preterm infants who were born prematurely but did not develop ROP, tested between 8 and 47 weeks (2–11 months) postterm age. Infants were presented with chromatic and luminance drifting sinusoidal gratings, which appeared randomly on the left or right side of the monitor on each trial. The contrast of the stimuli varied across trials and was defined in terms of root mean squared cone contrast for long- and medium-wavelength cones. Results Between 8 and 25 weeks postterm, ROP infants had significantly worse CS, and there was a trend for greater impairment for Luminance than Chromatic CS. This delay was not seen at older ages between 26 and 47 weeks postterm. Conclusions These findings are consistent with the concept that early maturation of the M pathway is vulnerable to biological insult, as in the case of ROP, to a greater extent than is the P pathway. PMID:23744448

Duration of the peak of adolescent growth spurt in class i and ii malocclusion subjects using a cervical vertebrae maturation analysis.

PubMed

Salazar-Lazo, Rodrigo; Arriola-Guillén, Luis E; Flores-Mir, Carlos

2014-01-01

The aim of the present work was to determine the duration of the adolescent peak growth spurt using cervical vertebral maturation analysis in class I and II malocclusion subjects. The study was conducted on a sample which consisted of 154 lateral cephalograms of children and adolescents aged 9-15 years (84 females and 70 males). The evaluation of skeletal maturation stage was performed using a visual morphological analysis of CS3 and CS4 cervical vertebrae. The sagittal skeletal relation was evaluated according to Steiner analysis. Descriptive statistics were used to summarize chronological age in each malocclusion group and for each CS3 and CS4 skeletal maturation stage. Due to a lack of normal distribution, comparisons of CS3 and CS4 age intervals on class I and II subjects were compared using the Mann-Whitney U test for independent samples. The results show that the mean duration of the adolescent peak growth spurt was 10 months between CS3 and CS4 stages in class I malocclusion subjects, whereas in class II malocclusion patients the duration was 6 months. This difference of 4 months was statistically significant (p<0.001). Finally, a clinically significant difference of 4 months in the duration of the adolescent peak growth spurt for class I and II malocclusion subjects was identified.

Compressed-Sensing Multi-Spectral Imaging of the Post-Operative Spine

PubMed Central

Worters, Pauline W.; Sung, Kyunghyun; Stevens, Kathryn J.; Koch, Kevin M.; Hargreaves, Brian A.

2012-01-01

Purpose To apply compressed sensing (CS) to in vivo multi-spectral imaging (MSI), which uses additional encoding to avoid MRI artifacts near metal, and demonstrate the feasibility of CS-MSI in post-operative spinal imaging. Materials and Methods Thirteen subjects referred for spinal MRI were examined using T2-weighted MSI. A CS undersampling factor was first determined using a structural similarity index as a metric for image quality. Next, these fully sampled datasets were retrospectively undersampled using a variable-density random sampling scheme and reconstructed using an iterative soft-thresholding method. The fully- and under-sampled images were compared by using a 5-point scale. Prospectively undersampled CS-MSI data were also acquired from two subjects to ensure that the prospective random sampling did not affect the image quality. Results A two-fold outer reduction factor was deemed feasible for the spinal datasets. CS-MSI images were shown to be equivalent or better than the original MSI images in all categories: nerve visualization: p = 0.00018; image artifact: p = 0.00031; image quality: p = 0.0030. No alteration of image quality and T2 contrast was observed from prospectively undersampled CS-MSI. Conclusion This study shows that the inherently sparse nature of MSI data allows modest undersampling followed by CS reconstruction with no loss of diagnostic quality. PMID:22791572

Correlation between k-space sampling pattern and MTF in compressed sensing MRSI.

PubMed

Heikal, A A; Wachowicz, K; Fallone, B G

2016-10-01

To investigate the relationship between the k-space sampling patterns used for compressed sensing MR spectroscopic imaging (CS-MRSI) and the modulation transfer function (MTF) of the metabolite maps. This relationship may allow the desired frequency content of the metabolite maps to be quantitatively tailored when designing an undersampling pattern. Simulations of a phantom were used to calculate the MTF of Nyquist sampled (NS) 32 × 32 MRSI, and four-times undersampled CS-MRSI reconstructions. The dependence of the CS-MTF on the k-space sampling pattern was evaluated for three sets of k-space sampling patterns generated using different probability distribution functions (PDFs). CS-MTFs were also evaluated for three more sets of patterns generated using a modified algorithm where the sampling ratios are constrained to adhere to PDFs. Strong visual correlation as well as high R 2 was found between the MTF of CS-MRSI and the product of the frequency-dependant sampling ratio and the NS 32 × 32 MTF. Also, PDF-constrained sampling patterns led to higher reproducibility of the CS-MTF, and stronger correlations to the above-mentioned product. The relationship established in this work provides the user with a theoretical solution for the MTF of CS MRSI that is both predictable and customizable to the user's needs.

Ultrafast dynamic contrast-enhanced mri of the breast using compressed sensing: breast cancer diagnosis based on separate visualization of breast arteries and veins.

PubMed

Onishi, Natsuko; Kataoka, Masako; Kanao, Shotaro; Sagawa, Hajime; Iima, Mami; Nickel, Marcel Dominik; Toi, Masakazu; Togashi, Kaori

2018-01-01

To evaluate the feasibility of ultrafast dynamic contrast-enhanced (UF-DCE) magnetic resonance imaging (MRI) with compressed sensing (CS) for the separate identification of breast arteries/veins and perform temporal evaluations of breast arteries and veins with a focus on the association with ipsilateral cancers. Our Institutional Review Board approved this study with retrospective design. Twenty-five female patients who underwent UF-DCE MRI at 3T were included. UF-DCE MRI consisting of 20 continuous frames was acquired using a prototype 3D gradient-echo volumetric interpolated breath-hold sequence including a CS reconstruction: temporal resolution, 3.65 sec/frame; spatial resolution, 0.9 × 1.3 × 2.5 mm. Two readers analyzed 19 maximum intensity projection images reconstructed from subtracted images, separately identified breast arteries/veins and the earliest frame in which they were respectively visualized, and calculated the time interval between arterial and venous visualization (A-V interval) for each breast. In total, 49 breasts including 31 lesions (breast cancer, 16; benign lesion, 15) were identified. In 39 of the 49 breasts (breasts with cancers, 16; breasts with benign lesions, 10; breasts with no lesions, 13), both breast arteries and veins were separately identified. The A-V intervals for breasts with cancers were significantly shorter than those for breasts with benign lesions (P = 0.043) and no lesions (P = 0.007). UF-DCE MRI using CS enables the separate identification of breast arteries/veins. Temporal evaluations calculating the time interval between arterial and venous visualization might be helpful in the differentiation of ipsilateral breast cancers from benign lesions. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:97-104. © 2017 International Society for Magnetic Resonance in Medicine.

Plasticity of the human visual system after retinal gene therapy in patients with Leber’s congenital amaurosis

PubMed Central

Ashtari, Manzar; Zhang, Hui; Cook, Philip A.; Cyckowski, Laura L.; Shindler, Kenneth S.; Marshall, Kathleen A.; Aravand, Puya; Vossough, Arastoo; Gee, James C.; Maguire, Albert M.; Baker, Chris I.; Bennett, Jean

2015-01-01

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber’s congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy. PMID:26180100

PathFinder: reconstruction and dynamic visualization of metabolic pathways.

PubMed

Goesmann, Alexander; Haubrock, Martin; Meyer, Folker; Kalinowski, Jörn; Giegerich, Robert

2002-01-01

Beyond methods for a gene-wise annotation and analysis of sequenced genomes new automated methods for functional analysis on a higher level are needed. The identification of realized metabolic pathways provides valuable information on gene expression and regulation. Detection of incomplete pathways helps to improve a constantly evolving genome annotation or discover alternative biochemical pathways. To utilize automated genome analysis on the level of metabolic pathways new methods for the dynamic representation and visualization of pathways are needed. PathFinder is a tool for the dynamic visualization of metabolic pathways based on annotation data. Pathways are represented as directed acyclic graphs, graph layout algorithms accomplish the dynamic drawing and visualization of the metabolic maps. A more detailed analysis of the input data on the level of biochemical pathways helps to identify genes and detect improper parts of annotations. As an Relational Database Management System (RDBMS) based internet application PathFinder reads a list of EC-numbers or a given annotation in EMBL- or Genbank-format and dynamically generates pathway graphs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zabawa, P.; Wakim, A.; Haruza, M.

We report production of ultracold X {sup 1}{Sigma}{sup +}(v{sup ''}=0) NaCs molecules via photoassociation. We utilize a combination of spectroscopic techniques to determine formation pathways and label ground-state samples. Efficient free-bound excitation occurs due to coupling between B {sup 1}{Pi} and neighboring electronic states in the Na 3S+Cs 6P complex. An f-wave shape resonance contributes to formation of a rotationally pure sample of X {sup 1}{Sigma}{sup +}(v{sup ''}=0,J{sup ''}=1) molecules.

Neuro-inflammatory response in rats chronically exposed to (137)Cesium.

PubMed

Lestaevel, Philippe; Grandcolas, Line; Paquet, François; Voisin, Philippe; Aigueperse, Jocelyne; Gourmelon, Patrick

2008-03-01

After the Chernobyl nuclear accident, behavioural disorders and central nervous system diseases were frequently observed in populations living in the areas contaminated by (137)Cs. Until now, these neurological disturbances were not elucidated, but the presence of a neuro-inflammatory response could be one explanation. Rats were exposed for 3 months to drinking water contaminated with (137)Cs at a dose of 400Bqkg(-1), which is similar to that ingested by the population living in contaminated areas in the former USSR countries. Pro-inflammatory and anti-inflammatory cytokine genes were assessed by real-time PCR in the frontal cortex and the hippocampus. At this level of exposure, gene expression of TNF-alpha and IL-6 increased in the hippocampus and gene expression of IL-10 increased in the frontal cortex. Concentration of TNF-alpha, measured by ELISA assays, was also increased in the hippocampus. The central NO-ergic pathway was also studied: iNOS gene expression and cNOS activity were significantly increased in the hippocampus. In conclusion, this study showed for the first time that sub-chronic exposure with post-accidental doses of (137)Cs leads to molecular modifications of pro- and anti-inflammatory cytokines and NO-ergic pathway in the brain. This neuro-inflammatory response could contribute to the electrophysiological and biochemical alterations observed after chronic exposure to (137)Cs.

Long non-coding RNA expression patterns in lung tissues of chronic cigarette smoke induced COPD mouse model.

PubMed

Zhang, Haiyun; Sun, Dejun; Li, Defu; Zheng, Zeguang; Xu, Jingyi; Liang, Xue; Zhang, Chenting; Wang, Sheng; Wang, Jian; Lu, Wenju

2018-05-15

Long non-coding RNAs (lncRNAs) have critical regulatory roles in protein-coding gene expression. Aberrant expression profiles of lncRNAs have been observed in various human diseases. In this study, we investigated transcriptome profiles in lung tissues of chronic cigarette smoke (CS)-induced COPD mouse model. We found that 109 lncRNAs and 260 mRNAs were significantly differential expressed in lungs of chronic CS-induced COPD mouse model compared with control animals. GO and KEGG analyses indicated that differentially expressed lncRNAs associated protein-coding genes were mainly involved in protein processing of endoplasmic reticulum pathway, and taurine and hypotaurine metabolism pathway. The combination of high throughput data analysis and the results of qRT-PCR validation in lungs of chronic CS-induced COPD mouse model, 16HBE cells with CSE treatment and PBMC from patients with COPD revealed that NR_102714 and its associated protein-coding gene UCHL1 might be involved in the development of COPD both in mouse and human. In conclusion, our study demonstrated that aberrant expression profiles of lncRNAs and mRNAs existed in lungs of chronic CS-induced COPD mouse model. From animal models perspective, these results might provide further clues to investigate biological functions of lncRNAs and their potential target protein-coding genes in the pathogenesis of COPD.

NO CHANGES IN SERUM CONCENTRATIONS OF INTERLEUKIN 10 (IL-10) AND INTERFERON γ (IF-γ) BEFORE AND AFTER TREATMENT OF THE THYROID EYE DISEASE (TED)

PubMed Central

Laban-Gučeva, Nevenka; Antova, Magdalena; Bogoev, Milco

2007-01-01

TED is a severe eye disease leading in rare cases to decrease of sight, optic nerve compression and blindness. Recently, significant progresses in understanding the disease have been done. Nevertheless, the treatment of the disease, especially in its severe form remains challenging. Glucocorticoids (GC) have been the basis of the treatment for a long time. Orbital irradiation (OI) and optical decompression (OD) are also used in managing the severe forms of TED. Somatostatin, intravenous immunoglobulin have been also used, with conflicting results. Regarding the potential for the treatment of TED with cytokine antagonists, controlled clinical studies are not available. Since cytokines play an important role in the pathogenesis of the TED, they seemed to be logical choice for modern TED treatment. It has been shown that both Th1 (interleukin-2, tumor necrosis factor γ, interleukin γ) and Th2 (interleukin-4,-5-,-10) profile T cells are activated in the TED. We therefore measured interleukin-γ, IF-γ and interleukin -10 (IL-10)(Th1 and Th2 pattern) to assess its relationship to the course of the disease. This paper shows that both Th1 (Il-2) and Th2 (If-γ) pathways represented by those two cytokines are not involved (Il-10 before 2,29±5,23 and after treatment 3,77±8,44; IF γ before 0,50±0,24 and after treatment 0,35±0,19). No relationship to the response to treatment was found. GC resulted in positive response in 8/22 patients, OI (12 patients) given after CS therapy, resulted in a response in all patients. Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD in two patients, who both recovered visual acuity and proptosis fell under 25mm Hertel. PMID:18039196

No changes in serum concentrations of interleukin 10 (IL-10) and interferon gamma (IF-gamma) before and after treatment of the thyroid eye disease (TED).

PubMed

Laban-Guceva, Nevenka; Antova, Magdalena; Bogoev, Milco

2007-11-01

TED is a severe eye disease leading in rare cases to decrease of sight, optic nerve compression and blindness. Recently, significant progresses in understanding the disease have been done. Nevertheless, the treatment of the disease, especially in its severe form remains challenging. Glucocorticoids (GC) have been the basis of the treatment for a long time. Orbital irradiation (OI) and optical decompression (OD) are also used in managing the severe forms of TED. Somatostatin, intravenous immunoglobulin have been also used, with conflicting results. Regarding the potential for the treatment of TED with cytokine antagonists, controlled clinical studies are not available. Since cytokines play an important role in the pathogenesis of the TED, they seemed to be logical choice for modern TED treatment. It has been shown that both Th1 (interleukin-2, tumor necrosis factor gamma, interleukin gamma) and Th2 (interleukin -4, -5, -10) profile T cells are activated in the TED. We therefore measured interleukin-gamma, IF-gamma and interleukin -10 (IL-10)(Th1 and Th2 pattern) to assess its relationship to the course of the disease. This paper shows that both Th1 (IL-2) and Th2 (IF-gamma) pathways represented by those two cytokines are not involved (IL-10 before 2.29+/-5.23 and after treatment 3.77+/-8.44; IF gamma before 0.50+/-0.24 and after treatment 0.35+/-0.19). No relationship to the response to treatment was found. GC resulted in positive response in 8/22 patients, OI (12 patients) given after CS therapy, resulted in a response in all patients. Increase in proptosis, loss of visual acuity is spite of CS treatment prompted OD in two patients, who both recovered visual acuity and proptosis fell under 25 mm Hertel.

Femtosecond-Assisted LASIK Versus PRK: Comparison of 6-Month Visual Acuity and Quality Outcome for High Myopia.

PubMed

Hashemi, Hassan; Miraftab, Mohammad; Ghaffari, Reza; Asgari, Soheila

2016-11-01

To compare the results of femtosecond-assisted laser in situ keratomileusis (femto-LASIK) and photorefractive keratectomy with mitomycin C (PRK-MMC) for the correction of myopia more than 7.0 diopters (D). In this comparative nonrandomized trial, 60 eyes (30 eyes in each group) were enrolled. Patients were tested for uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent, ocular and corneal aberrations, and contrast sensitivity (CS) before surgery and at 3 and 6 months postoperatively. Mean preoperative myopia was -8.65±1.51 and -8.04±1.70 D in the femto-LASIK and PRK-MMC groups, respectively (P=0.149). Intergroup differences in baseline indices were not statistically significant. At 6 months after surgery, UDVA showed an improving trend, but it was better in the femto-LASIK group (P=0.026). CDVA in the two groups remained similarly unchanged (P=0.170). For the femto-LASIK and PRK-MMC groups, the safety indices were 1.01±0.05 and 1.01±0.14 (P=0.949), respectively, and the efficacy indices were 0.99±0.07 and 0.93±0.22 (P=0.192), respectively. Comparing CS, only CS18 showed a significantly greater decrease in the femto-LASIK group compared with the PRK-MMC group (P=0.016). Intergroup differences were not statistically significant in other spatial frequencies. Changes in the ocular and corneal higher order aberrations were not statistically different between the two groups except ocular coma, which increased in the femto-LASIK group (P=0.041). Femto-LASIK improves UDVA better than PRK-MMC in high myopia. However, because of increased coma, the quality of vision is reduced. In other words, visual acuity outcome is better with femto-LASIK and visual quality outcome is better with PRK-MMC.

A feasibility study for compressed sensing combined phase contrast MR angiography reconstruction

NASA Astrophysics Data System (ADS)

Lee, Dong-Hoon; Hong, Cheol-Pyo; Lee, Man-Woo; Han, Bong-Soo

2012-02-01

Phase contrast magnetic resonance angiography (PC MRA) is a technique for flow velocity measurement and vessels visualization, simultaneously. The PC MRA takes long scan time because each flow encoding gradients which are composed bipolar gradient type need to reconstruct the angiography image. Moreover, it takes more image acquisition time when we use the PC MRA at the low-tesla MRI system. In this study, we studied and evaluation of feasibility for CS MRI reconstruction combined PC MRA which data acquired by low-tesla MRI system. We used non-linear reconstruction algorithm which named Bregman iteration for CS image reconstruction and validate the usefulness of CS combined PC MRA reconstruction technique. The results of CS reconstructed PC MRA images provide similar level of image quality between fully sampled reconstruction data and sparse sampled reconstruction using CS technique. Although our results used half of sampling ratio and do not used specification hardware device or performance which are improving the temporal resolution of MR image acquisition such as parallel imaging reconstruction using phased array coil or non-cartesian trajectory, we think that CS combined PC MRA technique will be helpful to increase the temporal resolution and at low-tesla MRI system.

Causes of childhood blindness in Ghana: results from a blind school survey in Upper West Region, Ghana, and review of the literature.

PubMed

Huh, Grace J; Simon, Judith; Grace Prakalapakorn, S

2017-06-13

Data on childhood blindness in Ghana are limited. The objectives of this study were to determine the major causes of childhood blindness and severe visual impairment (SVI) at Wa Methodist School for the Blind in Northern Ghana, and to compare our results to those published from other studies conducted in Ghana. In this retrospective study, data from an eye screening at Wa Methodist School in November 2014 were coded according to the World Health Organization/Prevention of Blindness standardized reporting methodology. Causes of blindness/SVI were categorized anatomically and etiologically, and were compared to previously published studies. Of 190 students screened, the major anatomical causes of blindness/SVI were corneal scar/phthisis bulbi (CS/PB) (n = 28, 15%) and optic atrophy (n = 23, 12%). The major etiological causes of blindness/SVI were unknown (n = 114, 60%). Eighty-three (44%) students became blind before age one year. Of four published blind school surveys conducted in Ghana, CS/PB was the most common anatomical cause of childhood blindness. Over time, the prevalence of CS/PB within blind schools decreased in the north and increased in the south. Measles-associated visual loss decreased from 52% in 1987 to 10% in 2014 at Wa Methodist School. In a blind school in northern Ghana, CS/PB was the major anatomical cause of childhood blindness/SVI. While CS/PB has been the most common anatomical cause of childhood blindness reported in Ghana, there may be regional changes in its prevalence over time. Being able to identify regional differences may guide future public health strategies to target specific causes.

Radioecological indexes of fallout measurements from the Fukushima nuclear accident

NASA Astrophysics Data System (ADS)

Manolopoulou, Metaxia; Stoulos, Stylianos; Ioannidou, Alexandra; Vagena, Eleni

2014-05-01

Fallout from the Fukushima nuclear accident has been monitored for about 1 month in Thessaloniki, Northern Greece. Three different radionuclides, one short-lived, one relatively long-lived and one long- lived fission product were identified in air, grass and milk samples. The 131I, 137Cs and 134Cs activity concentrations in air reached 497, 145 and 126 μBqm-3, respectively on 4 April, 2011. These radionuclides are of particular concern regarding their transfer from the environment to population through the ingestion pathways for the assessment of the Fukushima accident consequences. Radioecological indexes (eco-indexes) of fallout measurements in the air-grass-cow-milk-man pathway for 131I were determined, as they are related to radiological impact of the Fukushima derived radionuclides on the public and environment.

Browns Ferry Nuclear Plant low-level radwaste storage facility ground-water pathway analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boggs, J.M.

1982-10-01

The proposed low-level radwaste storage facility (LLRWSF) at Browns Ferry Nuclear Plant is underlain by soils having low hydraulic conductivity and high sorptive capacity which greatly reduce the risks associated with a potential contaminant excursion. A conservative ground-water pathway accident analysis using flow and solute transport modeling techniques indicates that without interdiction the concentrations of the five radionuclides of concern (Sr-90, Cs-137, Cs-134, Co-60, and Mn-54) would be well below 10 CFR Part 20 criteria at downgradient receptors. These receptors include a possible future private water well located near the eastern site boundary and Wheeler Reservoir. Routine ground-water monitoring ismore » not recommended at the LLRWSF except in the unlikely event of an accident.« less

Comparative study of visual pathways in owls (Aves: Strigiformes).

PubMed

Gutiérrez-Ibáñez, Cristián; Iwaniuk, Andrew N; Lisney, Thomas J; Wylie, Douglas R

2013-01-01

Although they are usually regarded as nocturnal, owls exhibit a wide range of activity patterns, from strictly nocturnal, to crepuscular or cathemeral, to diurnal. Several studies have shown that these differences in the activity pattern are reflected in differences in eye morphology and retinal organization. Despite the evidence that differences in activity pattern among owl species are reflected in the peripheral visual system, there has been no attempt to correlate these differences with changes in the visual regions in the brain. In this study, we compare the relative size of nuclei in the main visual pathways in nine species of owl that exhibit a wide range of activity patterns. We found marked differences in the relative size of all visual structures among the species studied, both in the tectofugal and the thalamofugal pathway, as well in other retinorecipient nuclei, including the nucleus lentiformis mesencephali, the nucleus of the basal optic root and the nucleus geniculatus lateralis, pars ventralis. We show that the barn owl (Tyto alba), a species widely used in the study of the integration of visual and auditory processing, has reduced visual pathways compared to strigid owls. Our results also suggest there could be a trade-off between the relative size of visual pathways and auditory pathways, similar to that reported in mammals. Finally, our results show that although there is no relationship between activity pattern and the relative size of either the tectofugal or the thalamofugal pathway, there is a positive correlation between the relative size of both visual pathways and the relative number of cells in the retinal ganglion layer. Copyright © 2012 S. Karger AG, Basel.

Reading impairment in schizophrenia: dysconnectivity within the visual system.

PubMed

Vinckier, Fabien; Cohen, Laurent; Oppenheim, Catherine; Salvador, Alexandre; Picard, Hernan; Amado, Isabelle; Krebs, Marie-Odile; Gaillard, Raphaël

2014-01-01

Patients with schizophrenia suffer from perceptual visual deficits. It remains unclear whether those deficits result from an isolated impairment of a localized brain process or from a more diffuse long-range dysconnectivity within the visual system. We aimed to explore, with a reading paradigm, the functioning of both ventral and dorsal visual pathways and their interaction in schizophrenia. Patients with schizophrenia and control subjects were studied using event-related functional MRI (fMRI) while reading words that were progressively degraded through word rotation or letter spacing. Reading intact or minimally degraded single words involves mainly the ventral visual pathway. Conversely, reading in non-optimal conditions involves both the ventral and the dorsal pathway. The reading paradigm thus allowed us to study the functioning of both pathways and their interaction. Behaviourally, patients with schizophrenia were selectively impaired at reading highly degraded words. While fMRI activation level was not different between patients and controls, functional connectivity between the ventral and dorsal visual pathways increased with word degradation in control subjects, but not in patients. Moreover, there was a negative correlation between the patients' behavioural sensitivity to stimulus degradation and dorso-ventral connectivity. This study suggests that perceptual visual deficits in schizophrenia could be related to dysconnectivity between dorsal and ventral visual pathways. © 2013 Published by Elsevier Ltd.

Direction of attention bias to threat relates to differences in fear acquisition and extinction in anxious children.

PubMed

Waters, Allison M; Kershaw, Rachel

2015-01-01

Anxious children show attention biases towards and away from threat stimuli. Moreover, threat avoidance compared to vigilance predicts a poorer outcome from exposure-based treatments, such as cognitive-behavioural therapy (CBT), yet the mechanisms underlying this differential response are unclear. Pavlovian fear conditioning is a widely accepted theory to explain the acquisition and extinction of fear, including exposure-based treatments, such as CBT. In typical fear conditioning experiments, anxious children have shown larger physiological responses to an aversive unconditional stimulus (i.e., US on CS+ trials) and to non-reinforced stimuli (CS-) during fear acquisition and to both CSs during fear extinction compared to non-anxious peers. This study examined whether threat avoidance compared to threat vigilance was related to differences in fear acquisition and extinction in anxious children. Thirty-four clinically-anxious children completed a visual probe task including angry-neutral face pairs to determine the direction of threat attention bias as well as a discriminant conditioning and extinction task in which a geometric shape CS+ was paired with an aversive tone US, while the CS- geometric shape was always presented alone during acquisition trials. Both CSs were presented alone during extinction trials. Fear acquisition and extinction were indexed by skin conductance responses (SCR) and subjective measures. Children were classified as threat vigilant (N = 18) and threat avoidant (n = 16) based on the direction of threat attention bias on the visual probe task. During acquisition, threat avoidant relative to threat vigilant anxious children displayed larger orienting SCRs to both CSs during the first block of trials and larger third interval SCRs to the US on CS+ trials as well as on CS- trials. During extinction, threat avoidant anxious children showed delayed extinction of SCRs to both the CS+ and CS- and reported higher subjective anxiety ratings after extinction compared to threat vigilant anxious children. Threat avoidant anxious children may be more reactive physiologically to novel cues and to stimuli that become associated with threat and this may interfere with extinction learning. These findings could help explain previous evidence that threat avoidant anxious children do not respond as well as threat vigilant anxious children to exposure-based CBT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Parallel neural pathways in higher visual centers of the Drosophila brain that mediate wavelength-specific behavior

PubMed Central

Otsuna, Hideo; Shinomiya, Kazunori; Ito, Kei

2014-01-01

Compared with connections between the retinae and primary visual centers, relatively less is known in both mammals and insects about the functional segregation of neural pathways connecting primary and higher centers of the visual processing cascade. Here, using the Drosophila visual system as a model, we demonstrate two levels of parallel computation in the pathways that connect primary visual centers of the optic lobe to computational circuits embedded within deeper centers in the central brain. We show that a seemingly simple achromatic behavior, namely phototaxis, is under the control of several independent pathways, each of which is responsible for navigation towards unique wavelengths. Silencing just one pathway is enough to disturb phototaxis towards one characteristic monochromatic source, whereas phototactic behavior towards white light is not affected. The response spectrum of each demonstrable pathway is different from that of individual photoreceptors, suggesting subtractive computations. A choice assay between two colors showed that these pathways are responsible for navigation towards, but not for the detection itself of, the monochromatic light. The present study provides novel insights about how visual information is separated and processed in parallel to achieve robust control of an innate behavior. PMID:24574974

Identification and bioinformatics comparison of two novel phosphatases in monoecious and gynoecious cucumber lines

NASA Astrophysics Data System (ADS)

Pawełkowicz, Magdalena E.; Wojcieszek, Michał; Osipowski, Paweł; Krzywkowski, Tomasz; PlÄ der, Wojciech; Przybecki, Zbigniew

2016-09-01

Two Arabidopsis thaliana genes from the PP2C family of protein phosphatases (AtABI1 and AtABI2) were used to find orthologous genes in the Cucumis sativus L. cv. Borszczagowski (cucumber) genome. Cucumber has been used as a model plant for sex expression studies because although it has been defined as a monoecious species, numerous genotypes are known to produce only female, only male, or hermaphroditic flowers. We identified two new orthologous genes of AtABI1 and AtABI2 in the cucumber genome and named them CsABI1 and CsABI2. To determine the relationships between the regulation of CsABI1 and CsABI2 and flower morphogenesis in cucumber, we performed various computational analyses to define the structure of the genes, and to predict regulatory elements and protein motifs in their sequences. We also performed an expression analysis to identify differences in the expression levels of CsABI1 and CsABI2 in vegetative and generative tissues (leaf, shoot apex, and flower buds) of monoecious (B10) and gynoecious (2gg) cucumber lines. We found that the expressions of CsABI1 and CsABI2 differed in male and female floral buds, and correlated these findings with the abscisic acid signaling pathways in male and female flowers.

Long term behavior of TEPCO FNPP1 derived radiocaesium in the North Pacific Ocean through the end of 2016: A review

NASA Astrophysics Data System (ADS)

Aoyama, Michio; Hamajima, Yasunori; Inomata, Yayoi; Kumamoto, Yuichiro; Oka, Eitarou; Tsubono, Takaki; Tsumune, Daisuke

2017-04-01

1, Two major source terms of radiocaesium to the Ocean There are two major sources of radionuclides to the environment derived by the TEPCO Fukushima Dai-ichi Nuclear Power Plant (FNPP1) accident in 2011. The largest and earliest source of artificial radionuclide was atmospheric release from three melt down cores of FNPP1, which led to atmospheric deposition on both land and in the ocean. Total amount of atmospheric release of 137Cs was estimated to be 15.2-20.4 PBq ( and same amount of 134Cs) (Aoyama et al., 2016). About 20 % of released radiocaesium fell on land and 80% of released radiocaesium fell on the ocean. Therefore 11.7-14.8 PBq of 137Cs was injected in the North Pacific as atmospheric deposition. Second largest source was the direct discharge of contaminated waters to the ocean since 26 March 2011 and peaked on 6 April 2011 (Tsumune et al., 2012). Total amount of directly released 137Cs was estimated to be 3.5 +- 0.7 PBq. A combined input to the North Pacific was therefore 15.2 - 18.3 PBq. 2, Three major pathways of FNPP1 derived radiocaesium in the North Pacific The fastest pathway of radiocaesium might be surface. FNPP1-derived radiocaesium injected at north of Kuroshio front by atmospheric deposition and direct discharge spread eastward in surface water by the North Pacific Current across the mid-latitude North Pacific (Aoyama et al., 2016). A model simulation by Tsubono et al.(2016) also shows good agreement with the observed radiocaesium activities in the North Pacific. The second pathway is formation of central mode water (CMW). A maximum of radiocaesium activity in June/July 2012 was observed at potential densities of 26.1-26.3 at 34 deg. N-39 deg. N along 165 deg. E, which correspond to 400 meters depth. The density is in a range of density of CMW and radiocaesium activity was higher than those in the surrounding waters, including STMW. In June-July 2015 and June 2016 at 36 deg. N-44 deg.N, 165 deg. E - 170 deg. E, we observe very week signal of FNPP1 radiocaesium, which means that subducted radiocaesium might have moved eastward from this region. The third pathway is formation of subtropical mode water (STMW). FNPP1-derived radiocaesium injected at south of Kuroshio front by atmospheric deposition transported to southward rapidly due to formation of STMW at potential densities of 25.1-25.3. In 2015 along 165 deg. E, FNPP1 radiocaesium corresponding STMW spread entire subtropical gyre and a part of them reached 2 deg. N and recirculated in the subtropical gyre and reached Japanese coast. 3, Mass balance of FNPP1 radiocaesium in the North Pacific 134Cs inventory was estimated to be 8 PBq in surface layer in summer 2012 (Inomata unpublished). Kaeriyama et al. (2016) estimated that 134Cs inventory in STWM in 2012 was about 4 PBq. We believe that FNPP1 derived 134Cs injected in the North Pacific was 15.2 - 18.3 PBq. Therefore 134Cs inventory can be estimated 3-6 PBq in CMW at this moment based on a mass balance of FNPP1 radiocaesium.

Long-term decrease of atmospheric test {sup 137}Cs in the soil-prairie plant-milk pathway in southern Chile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuller, P. Ellies, A.; Handl, J.

1998-07-01

The time dependency of nuclear test {sup 137}Cs in soil, prairie plants, and milk was observed on pastures of seven dairy farms in the 10th Region, Chile, from 1982 to 1997, without any appreciable deposition of radioactive fallout after 1983. Whereas the {sup 137}Cs concentration in the soil decreased at a rate close to that of the radionuclide`s physical decay during the whole observation period, the rate of decrease of the {sup 137}Cs concentration in the prairie plants and in the milk, having been very rapid between 1982--1990, became slower between 1991--1997. The effective half-lives of the concentration in plantsmore » were found to be 5.6 y and 12 y during the first and second observation periods, respectively. Similar half-lives of 5.5 y and 13 y were found for the concentration decline in milk during each period. These data clearly demonstrate a reduction in the long-term decrease of the {sup 137}Cs plant uptake, and consequently in the decrease of the {sup 137}Cs concentration in milk, resulting from a decline of {sup 137}Cs availability for prairie plants in the Hapludand soils over the whole 15-y observation period.« less

Novel Cs-Based Upconversion Nanoparticles as Dual-Modal CT and UCL Imaging Agents for Chemo-Photothermal Synergistic Therapy.

PubMed

Liu, Yuxin; Li, Luoyuan; Guo, Quanwei; Wang, Lu; Liu, Dongdong; Wei, Ziwei; Zhou, Jing

2016-01-01

Lanthanide-based contrast agents have attracted increasing attention for their unique properties and potential applications in cancer theranostics. To date, many of these agents have been studied extensively in cells and small animal models. However, performance of these theranostic nanoparticles requires further improvement. In this study, a novel CsLu2F7:Yb,Er,Tm-based visual therapeutic platform was developed for imaging-guided synergistic cancer therapy. Due to the presence of the heavy alkali metal Cesium (Cs) in host lattice, the nanoplatform can provide a higher resolution X-ray CT imaging than many other reported lanthanide-based CT contrast agents. Furthermore, by using the targeted RGD motif, chemotherapy drug alpha-tocopheryl succinate (α-TOS), and photothermal coupling agent ICG, this nanoplatform simultaneously provides multifunctional imaging and targeted synergistic therapy. To demonstrate the theranostic performance of this novel nanoplatform in vivo, visual diagnosis in the small animal model was realized by UCL/CT imaging which was further integrated with targeted chemo-photothermal synergistic therapy. These results provided evidence for the successful construction of a novel lanthanide-based nanoplatform coupled with multimodal imaging diagnosis and potential application in synergistic cancer theranostics.

Extractability of 137Cs in Response to its Input Forms into Fukushima Forest Soils.

NASA Astrophysics Data System (ADS)

Mengistu, T. T.; Carasco, L.; Orjollet, D.; Coppin, F.

2017-12-01

In case of nuclear accidents like Fukushima disaster, the influence of 137Cs depositional forms (soluble and/or solid forms) on mineral soil of forest environment on its availability have not reported yet. Soluble (137Cs tagged ultra-pure water) and solid (137Cs contaminated litter-OL and fragmented litter-OF) input forms were mixed with the mineral soils collected under Fukushima coniferous and broadleaf forests. The mixtures then incubated under controlled laboratory condition to evaluate the extractability of 137Cs in soil over time in the presence of decomposition process through two extracting reagents- water and ammonium acetate. Results show that extracted 137Cs fraction with water was less than 1% for soluble input form and below detection limit for solid input form. On the same way with acetate reagent, the extracted 137Cs fraction ranged from 46 to 56% for soluble input and 2 to 15% for solid input, implying the nature of 137Cs contamination strongly influences the extractability and hence the mobility of 137Cs in soil. Although the degradation rate of the organic materials has been calculated in the range of 0.18 ± 0.1 to 0.24 ± 0.1 y-1, its impact on 137Cs extractability appeared very weak at least within the observation period, probably due to shorter time scale. Concerning the treatments of solid 137Cs input forms through acetate extraction, relatively more 137Cs has been extracted from broadleaf organic materials mixes (BL-OL & BL-OF) than the coniferous counterparts. This probably is due to the fact that the lignified coniferous organic materials (CED-OL & CED-OF) components tend to retain more 137Cs than that of the broadleaf. Generally, by extrapolating these observations in to a field context, one can expect more available 137Cs fraction in forest soil from wet depositional pathways such as throughfall and stemflow than those attached with organic materials like litter (OL) and its eco-processed forms (OF).

The Shape of the Maxillary Central Incisors and Its Correlation with Maxillary Anterior Papillary Display: A Clinical Study.

PubMed

Nichani, Ashish S; Ahmed, Arshia Zainab; Ranganath, V

2016-01-01

The aim of this study was to define shapes of maxillary central incisors and determine their relationship with the visual display of interdental papillae during smiling. A sample of 100 patients aged 20 to 25 years were recruited. Photographs were taken and gingival angle, crown width (CW), crown length (CL), contact surface (CS), CW/CL ratio, CS/CL ratio, gingival smile line (GSL), and interdental smile line (ISL) were measured. The data showed an increase in GA leading to an increase in CW and CS/CL ratio. Women showed a higher percentage of papillary display compared with men. This study reinforces the proposed hypothesis that the shape of the teeth and papilla affect the periodontium.

Active packaging from chitosan-titanium dioxide nanocomposite film for prolonging storage life of tomato fruit.

PubMed

Kaewklin, Patinya; Siripatrawan, Ubonrat; Suwanagul, Anawat; Lee, Youn Suk

2018-06-01

The feasibility of active packaging from chitosan (CS) and chitosan containing nanosized titanium dioxide (CT) to maintain quality and extend storage life of climacteric fruit was investigated. The CT nanocomposite film and CS film were fabricated using a solution casting method and used as active packaging to delay ripening process of cherry tomatoes. Changes in firmness, weight loss, a*/b* color, lycopene content, total soluble solid, ascorbic acid, and concentration of ethylene and carbon dioxide of the tomatoes packaged in CT film, CS film, and control (without CT or CS films) were monitored during storage at 20°C. Classification of fruit quality as a function of different packaging treatments was visualized using linear discriminant analysis. Tomatoes packaged in the CT film evolved lower quality changes than those in the CS film and control. The results suggested that the CT film exhibited ethylene photodegradation activity when exposed to UV light and consequently delayed the ripening process and changes in the quality of the tomatoes. Copyright © 2018 Elsevier B.V. All rights reserved.

The role of abscisic acid in regulating cucumber fruit development and ripening and its transcriptional regulation.

PubMed

Wang, Yanping; Wang, Ya; Ji, Kai; Dai, Shengjie; Hu, Ying; Sun, Liang; Li, Qian; Chen, Pei; Sun, Yufei; Duan, Chaorui; Wu, Yan; Luo, Hao; Zhang, Dian; Guo, Yangdong; Leng, Ping

2013-03-01

Cucumber (Cucumis sativus L.), a kind of fruit usually harvested at the immature green stage, belongs to non-climacteric fruit. To investigate the contribution of abscisic acid (ABA) to cucumber fruit development and ripening, variation in ABA level was investigated and a peak in ABA level was found in pulp before fruit get fully ripe. To clarify this point further, exogenous ABA was applied to cucumber fruits at two different development stages. Results showed that ABA application at the turning stage promotes cucumber fruit ripening, while application at the immature green stage had inconspicuous effects. In addition, with the purpose of understanding the transcriptional regulation of ABA, two partial cDNAs of CsNCED1 and CsNCED2 encoding 9-cis-epoxycarotenoid dioxygenase (NCED), a key enzyme in ABA biosynthetic pathway; one partial cDNA of CsCYP707A1 for 8'-hydroxylase, a key enzyme in the oxidative catabolism of ABA and two partial cDNAs of CsBG1 and CsBG2 for β-glucosidase (BG) that hydrolyzes ABA glucose ester (ABA-GE) to release active ABA were cloned from cucumber. The DNA and deduced amino acid sequences of these obtained genes respectively showed high similarities to their homologous genes in other plants. Real-time PCR analysis revealed that ABA content may be regulated by its biosynthesis (CsNCEDs), catabolism (CsCYP707A1) and reactivation genes (CsBGs) at the transcriptional level during cucumber fruit development and ripening, in response to ABA application, dehydration and pollination, among which CsNCED1, CsCYP707A1 and CsBG1 were highly expressed in pulp and may play more important roles in regulating ABA metabolism. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The high affinity K+ transporter AtHAK5 plays a physiological role in planta at very low K+ concentrations and provides a caesium uptake pathway in Arabidopsis.

PubMed

Qi, Zhi; Hampton, Corrina R; Shin, Ryoung; Barkla, Bronwyn J; White, Philip J; Schachtman, Daniel P

2008-01-01

Caesium (Cs(+)) is a potentially toxic mineral element that is released into the environment and taken up by plants. Although Cs(+) is chemically similar to potassium (K(+)), and much is known about K(+) transport mechanisms, it is not clear through which K(+) transport mechanisms Cs(+) is taken up by plant roots. In this study, the role of AtHAK5 in high affinity K(+) and Cs(+) uptake was characterized. It is demonstrated that AtHAK5 is localized to the plasma membrane under conditions of K(+) deprivation, when it is expressed. Growth analysis showed that AtHAK5 plays a role during severe K(+) deprivation. Under K(+)-deficient conditions in the presence of Cs(+), Arabidopsis seedlings lacking AtHAK5 had increased inhibition of root growth and lower Cs(+) accumulation, and significantly higher leaf chlorophyll concentrations than wild type. These data indicate that, in addition to transporting K(+) in planta, AtHAK5 also transports Cs(+). Further experiments showed that AtHAK5 mediated Cs(+) uptake into yeast cells and that, although the K(+) deficiency-induced expression of AtHAK5 was inhibited by low concentrations of NH(4)(+) in planta, Cs(+) uptake by yeast was stimulated by low concentrations of NH(4)(+). Interestingly, the growth of the Arabidopsis atakt1-1 mutant was more sensitive to Cs(+) than the wild type. This may be explained, in part, by increased expression of AtHAK5 in the atakt1-1 mutant. It is concluded that AtHAK5 is a root plasma membrane uptake mechanism for K(+) and Cs(+) under conditions of low K(+) availability.

Carbon Disulfide (CS2) Interference in Glucose Metabolism from Unconventional Oil and Gas Extraction and Processing Emissions.

PubMed

Rich, Alisa L; Patel, Jay T; Al-Angari, Samiah S

2016-01-01

Carbon disulfide (CS2) has been historically associated with the manufacturing of rayon, cellophane, and carbon tetrachloride production. This study is one of the first to identify elevated atmospheric levels of CS2 above national background levels and its mechanisms to dysregulate normal glucose metabolism. Interference in glucose metabolism can indirectly cause other complications (diabetes, neurodegenerative disease, and retinopathy), which may be preventable if proper precautions are taken. Rich et al found CS2 and 12 associated sulfide compounds present in the atmosphere in residential areas where unconventional shale oil and gas extraction and processing operations were occurring. Ambient atmospheric concentrations of CS2 ranged from 0.7 parts per billion by volume (ppbv) to 103 ppbv over a continuous 24-hour monitoring period. One-hour ambient atmospheric concentrations ranged from 3.4 ppbv to 504.6 ppbv. Using the U.S. Environmental Protection Agency Urban Air Toxic Monitoring Program study as a baseline comparison for atmospheric CS2 concentrations found in this study, it was determined that CS2 atmospheric levels were consistently elevated in areas where unconventional oil and gas extraction and processing occurred. The mechanisms by which CS2 interferes in normal glucose metabolism by dysregulation of the tryptophan metabolism pathway are presented in this study. The literature review found an increased potential for alteration of normal glucose metabolism in viscose rayon occupational workers exposed to CS2. Occupational workers in the energy extraction industry exposed to CS2 and other sulfide compounds may have an increased potential for glucose metabolism interference, which has been an indicator for diabetogenic effect and other related health impacts. The recommendation of this study is for implementation of regular monitoring of blood glucose levels in CS2-exposed populations as a preventative health measure.

Anomalous visual experiences, negative symptoms, perceptual organization and the magnocellular pathway in schizophrenia: a shared construct?

PubMed

Kéri, Szabolcs; Kiss, Imre; Kelemen, Oguz; Benedek, György; Janka, Zoltán

2005-10-01

Schizophrenia is associated with impaired visual information processing. The aim of this study was to investigate the relationship between anomalous perceptual experiences, positive and negative symptoms, perceptual organization, rapid categorization of natural images and magnocellular (M) and parvocellular (P) visual pathway functioning. Thirty-five unmedicated patients with schizophrenia and 20 matched healthy control volunteers participated. Anomalous perceptual experiences were assessed with the Bonn Scale for the Assessment Basic Symptoms (BSABS). General intellectual functions were evaluated with the revised version of the Wechsler Adult Intelligence Scale. The 1-9 version of the Continuous Performance Test (CPT) was used to investigate sustained attention. The following psychophysical tests were used: detection of Gabor patches with collinear and orthogonal flankers (perceptual organization), categorization of briefly presented natural scenes (rapid visual processing), low-contrast and frequency-doubling vernier threshold (M pathway functioning), isoluminant colour vernier threshold and high spatial frequency discrimination (P pathway functioning). The patients with schizophrenia were impaired on test of perceptual organization, rapid visual processing and M pathway functioning. There was a significant correlation between BSABS scores, negative symptoms, perceptual organization, rapid visual processing and M pathway functioning. Positive symptoms, IQ, CPT and P pathway measures did not correlate with these parameters. The best predictor of the BSABS score was the perceptual organization deficit. These results raise the possibility that multiple facets of visual information processing deficits can be explained by M pathway dysfunctions in schizophrenia, resulting in impaired attentional modulation of perceptual organization and of natural image categorization.

Cerebral Visual Impairment: Which Perceptive Visual Dysfunctions Can Be Expected in Children with Brain Damage? A Systematic Review

ERIC Educational Resources Information Center

Boot, F. H.; Pel, J. J. M.; van der Steen, J.; Evenhuis, H. M.

2010-01-01

The current definition of Cerebral Visual Impairment (CVI) includes all visual dysfunctions caused by damage to, or malfunctioning of, the retrochiasmatic visual pathways in the absence of damage to the anterior visual pathways or any major ocular disease. CVI is diagnosed by exclusion and the existence of many different causes and symptoms make…

Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

PubMed

Ashtari, Manzar; Zhang, Hui; Cook, Philip A; Cyckowski, Laura L; Shindler, Kenneth S; Marshall, Kathleen A; Aravand, Puya; Vossough, Arastoo; Gee, James C; Maguire, Albert M; Baker, Chris I; Bennett, Jean

2015-07-15

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy. Copyright © 2015, American Association for the Advancement of Science.

Cardio‐facio‐cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype–phenotype relationships and overlap with Costello syndrome

PubMed Central

Nava, Caroline; Hanna, Nadine; Michot, Caroline; Pereira, Sabrina; Pouvreau, Nathalie; Niihori, Tetsuya; Aoki, Yoko; Matsubara, Yoichi; Arveiler, Benoit; Lacombe, Didier; Pasmant, Eric; Parfait, Béatrice; Baumann, Clarisse; Héron, Delphine; Sigaudy, Sabine; Toutain, Annick; Rio, Marlène; Goldenberg, Alice; Leheup, Bruno; Verloes, Alain; Cavé, Hélène

2007-01-01

Cardio‐facio‐cutaneous (CFC) syndrome, Noonan syndrome (NS), and Costello syndrome (CS) are clinically related developmental disorders that have been recently linked to mutations in the RAS/MEK/ERK signalling pathway. This study was a mutation analysis of the KRAS, BRAF, MEK1 and MEK2 genes in a total of 130 patients (40 patients with a clinical diagnosis of CFC, 20 patients without HRAS mutations from the French Costello family support group, and 70 patients with NS without PTPN11 or SOS1 mutations). BRAF mutations were found in 14/40 (35%) patients with CFC and 8/20 (40%) HRAS‐negative patients with CS. KRAS mutations were found in 1/40 (2.5%) patients with CFC, 2/20 (10%) HRAS‐negative patients with CS and 4/70 patients with NS (5.7%). MEK1 mutations were found in 4/40 patients with CFC (10%), 4/20 (20%) HRAS‐negative patients with CS and 3/70 (4.3%) patients with NS, and MEK2 mutations in 4/40 (10%) patients with CFC. Analysis of the major phenotypic features suggests significant clinical overlap between CS and CFC. The phenotype associated with MEK mutations seems less severe, and is compatible with normal mental development. Features considered distinctive for CS were also found to be associated with BRAF or MEK mutations. Because of its particular cancer risk, the term “Costello syndrome” should only be used for patients with proven HRAS mutation. These results confirm that KRAS is a minor contributor to NS and show that MEK is involved in some cases of NS, demonstrating a phenotypic continuum between the clinical entities. Although some associated features appear to be characteristic of a specific gene, no simple rule exists to distinguish NS from CFC easily. PMID:17704260

HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette smoke and lipopolysaccharide.

PubMed

Shin, Na-Rae; Kim, Sung-Ho; Ko, Je-Won; Park, Sung-Hyeuk; Lee, In-Chul; Ryu, Jung-Min; Kim, Jong-Choon; Shin, In-Sik

2017-03-01

HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-α, interleukin (IL)-6 and IL-1β in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD.

Cyclosporin A reduces matrix metalloproteinases and collagen expression in dermal fibroblasts from regenerative FOXN1 deficient (nude) mice

PubMed Central

2013-01-01

Background Cyclosporin A (CsA), an immunosuppressive agent modifies the wound healing process through an influence on extracellular matrix metabolism. We have compared the effects of CsA on dermal fibroblasts from nude (FOXN1 deficient) mice, a genetic model of skin scarless healing, and from control (C57BL/6 J (B6) mice to evaluate metabolic pathways that appear to have important roles in the process of scarless healing/regeneration. Results High levels of matrix metalloproteinases (MMPs) and collagen III expression in dermal fibroblasts from nude (regenerative) mice were down-regulated by CsA treatment to the levels observed in dermal fibroblasts from B6 (non-regenerative) mice. In contrast, dermal fibroblasts from control mice respond to CsA treatment with a minor reduction of Mmps mRNA and 2.5-fold increase expression of collagen I mRNA. An in vitro migratory assay revealed that CsA treatment profoundly delayed the migratory behavior of dermal fibroblasts from both nude and control mice. Conclusion The data suggest that by alternation of the accumulation of extracellular matrix components CsA treatment stimulates the transition from a scarless to a scar healing. PMID:23547542

HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette smoke and lipopolysaccharide

PubMed Central

Shin, Na-Rae; Kim, Sung-Ho; Ko, Je-Won; Park, Sung-Hyeuk; Lee, In-Chul; Ryu, Jung-Min; Kim, Jong-Choon

2017-01-01

HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-α, interleukin (IL)-6 and IL-1β in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD. PMID:28400838

Regio-selectivity of the Oxidative C-S Bond Formation in Ergothioneine and Ovothiol Biosyntheses

PubMed Central

Song, Heng; Leninger, Maureen; Lee, Norman

2014-01-01

Ergothioneine (5) and ovothiol (8) are two novel thiol-containing natural products. Their C-S bonds are formed by oxidative coupling reactions catalyzed by EgtB and OvoA enzymes, respectively. In this work, it was discovered that besides catalyzing the oxidative coupling between histidine and cysteine (1 → 6 conversion), OvoA can also catalyze a direct oxidative coupling between hercynine (2) and cysteine (2 → 4 conversion), which can shorten the ergothioneine biosynthetic pathway by two steps. PMID:24016264

Long-Term Synaptic Changes in Two Input Pathways into the Lateral Nucleus of the Amygdala Underlie Fear Extinction

ERIC Educational Resources Information Center

Park, Junchol; Choi, June-Seek

2010-01-01

Plasticity in two input pathways into the lateral nucleus of the amygdala (LA), the medial prefrontal cortex (mPFC) and the sensory thalamus, have been suggested to underlie extinction, suppression of a previously acquired conditioned response (CR) following repeated presentations of the conditioned stimulus (CS). However, little is known about…

Protective effects of aspirin and vitamin C against corn syrup consumption-induced cardiac damage through sirtuin-1 and HIF-1α pathway.

PubMed

Aşcı, Halil; Saygın, Mustafa; Yeşilot, Şükriye; Topsakal, Şenay; Cankara, Fatma Nihan; Özmen, Özlem; Savran, Mehtap

2016-09-01

The aim of this study was to investigate the protective effects of aspirin (AS) and vitamin C (VC) against cardiac damage induced by chronic corn syrup (CS) consumption via a mechanism involving sirtuin-1 (ST-1), hypoxia-inducible factor-1α (HIF-1α), and the caspase-3 pathway in rats. Forty male Sprague-Dawley rats (14-16 weeks) that weighed 250-300 g were randomly distributed into 5 groups, each containing 8 rats: control group, CS+AS group, CS+VC group, CS+AS+VC group, and CS group. AS (10 mg/kg/day) and VC (200 mg/kg/day) were orally given to the rats. F30 (30% fructose syrup solution) was given to the rats in drinking water for 6 weeks. The rats were sacrificed by exsanguination 24 h after the last administration. Blood samples and tissue were collected for biochemical, histopathological, and immunohistochemical examinations. Non-parametric Kruskal-Wallis test and Mann-Whitney U test used for the parameters without normal distribution and ANOVA and post-hoc LSD tests were used for parameters with a normal distribution to compare groups. Uric acid, creatine kinase (CKMB), and lactate dehydrogenase (LDH) levels were increased in the CS group compared with the control group (1.45±0.39 and p=0.011; 3225.64±598.25 and p=0.004; 3906.83±1064.22 and p=0.002, respectively) and decreased in all the treatment groups. In addition, increased levels of MDA and decreased activity of CAT in the CS group (0.172±0.03 and p=0.000; 0.070±0.005 and p=0.007, respectively) were reversed with AS and VC therapy. A decrease in ST-1 activity and increases in caspase-3 and HIF-1 activities corrected by VC and AS therapy were observed. AS and VC, which display antioxidant and antiapoptotic activities, ameliorated cardiac damage induced by chronic fructose consumption by increasing the levels of ST-1 and decreasing the levels of HIF-1α and caspase-3.

Probiotic Bifidobacterium species stimulate human SLC26A3 gene function and expression in intestinal epithelial cells

PubMed Central

Kumar, Anoop; Hecht, Cameron; Priyamvada, Shubha; Anbazhagan, Arivarasu N.; Alakkam, Anas; Borthakur, Alip; Alrefai, Waddah A.; Gill, Ravinder K.

2014-01-01

SLC26A3, or downregulated in adenoma (DRA), plays a major role in mediating Cl− absorption in the mammalian intestine. Disturbances in DRA function and expression have been implicated in intestinal disorders such as congenital Cl− diarrhea and gut inflammation. We previously showed that an increase in DRA function and expression by Lactobacillus acidophilus and its culture supernatant (CS) might underlie antidiarrheal effects of this probiotic strain. However, the effects of Bifidobacterium species, important inhabitants of the human colon, on intestinal Cl−/HCO3− exchange activity are not known. Our current results demonstrate that CS derived from Bifidobacterium breve, Bifidobacterium infantis, and Bifidobacterium bifidum increased anion exchange activity in Caco-2 cells (∼1.8- to 2.4-fold). Consistent with the increase in DRA function, CS also increased the protein, as well as the mRNA, level of DRA (but not putative anion transporter 1). CS of all three Bifidobacterium sp. increased DRA promoter activity (−1,183/+114 bp) in Caco-2 cells (1.5- to 1.8-fold). Furthermore, the increase in DRA mRNA expression by CS of B. breve and B. infantis was blocked in the presence of the transcription inhibitor actinomycin D (5 μM) and the ERK1/2 MAPK pathway inhibitor U0126 (10 μM). Administration of live B. breve, B. infantis, and B. bifidum by oral gavage to mice for 24 h increased DRA mRNA and protein levels in the colon. These data demonstrate an upregulation of DRA via activation of the ERK1/2 pathway that may underlie potential antidiarrheal effects of Bifidobacterium sp. PMID:25143346

SHORT HYPOCOTYL1 Encodes a SMARCA3-Like Chromatin Remodeling Factor Regulating Elongation1[OPEN

PubMed Central

Bo, Kailiang; Behera, Tusar K.; Pandey, Sudhakar; Wen, Changlong; Wang, Yuhui; Simon, Philipp W.; Li, Yuhong

2016-01-01

In Arabidopsis (Arabidopsis thaliana), the UVR8-mediated signaling pathway is employed to attain UVB protection and acclimation to deal with low-dosage UVB (LDUVB)-induced stresses. Here, we identified SHORT HYPOCOTYL1 (SH1) in cucumber (Cucumis sativus), which regulates LDUVB-dependent hypocotyl elongation by modulating the UVR8 signaling pathway. We showed that hypocotyl elongation in cucumbers carrying the recessive sh1 allele was LDUVB insensitive and that Sh1 encoded a human SMARCA3-like chromatin remodeling factor. The allele frequency and distribution pattern at this locus among natural populations supported the wild cucumber origin of sh1 for local adaptation, which was under selection during domestication. The cultivated cucumber carries predominantly the Sh1 allele; the sh1 allele is nearly fixed in the semiwild Xishuangbanna cucumber, and the wild cucumber population is largely at Hardy-Weinberg equilibrium for the two alleles. The SH1 protein sequence was highly conserved among eukaryotic organisms, but its regulation of hypocotyl elongation in cucumber seems to be a novel function. While Sh1 expression was inhibited by LDUVB, its transcript abundance was highly correlated with hypocotyl elongation rate and the expression level of cell-elongation-related genes. Expression profiling of key regulators in the UVR8 signaling pathway revealed significant differential expression of CsHY5 between two near isogenic lines of Sh1. Sh1 and CsHY5 acted antagonistically at transcriptional level. A working model was proposed in which Sh1 regulates LDUVB-dependent hypocotyl elongation in cucumber through changing the chromatin states and thus the accessibility of CsHY5 in the UVR8 signaling pathway to promoters of LDUVB-responsive genes for hypocotyl elongation. PMID:27559036

Accessory pathway location affects brain natriuretic peptide level in patients with Wolff-Parkinson-White syndrome.

PubMed

Nakatani, Yosuke; Kumagai, Koji; Naito, Shigeto; Nakamura, Kohki; Minami, Kentaro; Nakano, Masahiro; Sasaki, Takehito; Kinugawa, Koichiro; Oshima, Shigeru

2017-01-01

The purpose of this study was to investigate the relationship between the accessory pathway location and brain natriuretic peptide (BNP) level in patients with Wolff-Parkinson-White (WPW) syndrome. We divided 102 WPW syndrome patients with normal left ventricular systolic function into four groups: those with manifest right (MR, n = 14), manifest septal (MS, n = 11), manifest left (ML, n = 30), and concealed (C, n = 47) accessory pathways. BNP level and electrophysiological properties, including difference in timing of the ventricular electrogram between the His bundle area and the distal coronary sinus area (His-CS delay), which indicate intraventricular dyssynchrony, were compared. BNP levels (pg/dl) were higher in the MR and MS groups than in the ML and C groups (MR, 64 ± 58; MS, 55 ± 45; ML, 17 ± 15; C, 25 ± 21; P < 0.001). AV intervals (ms) were shorter in the MR and MS groups than in the ML and C groups (MR, 76 ± 16; MS, 83 ± 6; ML, 101 ± 19; C, 136 ± 20; P < 0.001). His-CS delay (ms) was longer in the MR group than in the other groups (MR, 50 ± 15; MS, 21 ± 7; ML, 23 ± 10; C, 19 ± 8; P < 0.001). The AV interval (P < 0.01) and the His-CS delay (P < 0.001) were negatively and positively correlated, respectively, with the BNP level. Anterograde conduction with a right or septal accessory pathway increased the BNP level in WPW syndrome patients with normal cardiac function.

Chromatic and achromatic visual fields in relation to choroidal thickness in patients with high myopia: A pilot study.

PubMed

García-Domene, M C; Luque, M J; Díez-Ajenjo, M A; Desco-Esteban, M C; Artigas, J M

2018-02-01

To analyse the relationship between the choroidal thickness and the visual perception of patients with high myopia but without retinal damage. All patients underwent ophthalmic evaluation including a slit lamp examination and dilated ophthalmoscopy, subjective refraction, best corrected visual acuity, axial length, optical coherence tomography, contrast sensitivity function and sensitivity of the visual pathways. We included eleven eyes of subjects with high myopia. There are statistical correlations between choroidal thickness and almost all the contrast sensitivity values. The sensitivity of magnocellular and koniocellular pathways is the most affected, and the homogeneity of the sensibility of the magnocellular pathway depends on the choroidal thickness; when the thickness decreases, the sensitivity impairment extends from the center to the periphery of the visual field. Patients with high myopia without any fundus changes have visual impairments. We have found that choroidal thickness correlates with perceptual parameters such as contrast sensitivity or mean defect and pattern standard deviation of the visual fields of some visual pathways. Our study shows that the magnocellular and koniocellular pathways are the most affected, so that these patients have impairment in motion perception and blue-yellow contrast perception. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

User-centered evaluation of Arizona BioPathway: an information extraction, integration, and visualization system.

PubMed

Quiñones, Karin D; Su, Hua; Marshall, Byron; Eggers, Shauna; Chen, Hsinchun

2007-09-01

Explosive growth in biomedical research has made automated information extraction, knowledge integration, and visualization increasingly important and critically needed. The Arizona BioPathway (ABP) system extracts and displays biological regulatory pathway information from the abstracts of journal articles. This study uses relations extracted from more than 200 PubMed abstracts presented in a tabular and graphical user interface with built-in search and aggregation functionality. This paper presents a task-centered assessment of the usefulness and usability of the ABP system focusing on its relation aggregation and visualization functionalities. Results suggest that our graph-based visualization is more efficient in supporting pathway analysis tasks and is perceived as more useful and easier to use as compared to a text-based literature-viewing method. Relation aggregation significantly contributes to knowledge-acquisition efficiency. Together, the graphic and tabular views in the ABP Visualizer provide a flexible and effective interface for pathway relation browsing and analysis. Our study contributes to pathway-related research and biological information extraction by assessing the value of a multiview, relation-based interface that supports user-controlled exploration of pathway information across multiple granularities.

Morphogenesis and three-dimensional movement of the stomach during the human embryonic period.

PubMed

Kaigai, N; Nako, A; Yamada, S; Uwabe, C; Kose, K; Takakuwa, T

2014-05-01

The stomach develops as the local widening of the foregut after Carnegie stage (CS) 13 that moves in a dramatic and dynamic manner during the embryonic period. Using the magnetic resonance images of 377 human embryos, we present the morphology, morphometry, and three-dimensional movement of the stomach during CS16 and CS23. The stomach morphology revealed stage-specific features. The angular incisura and the cardia were formed at CS18. The change in the angular incisura angle was approximately 90° during CS19 and CS20, and was <90° after CS 21. The prominent formations of the fundus and the pylorus differentiate at around CS20. Morphometry of the stomach revealed that the stomach gradually becomes "deflected" during development. The stomach may appear to move to the left laterally and caudally due to its deflection and differential growth. The track of the reference points in the stomach may reflect the visual three-dimensional movement. The movement of point M, representing the movement of the greater curvature, was different from that of points C (cardia) and P (pyloric antrum). The P and C were located just around the midsagittal plane in all the stages observed. Point M moved in the caudal-left lateral direction until CS22. Moreover, the vector CP does not rotate around the dorsoventral axis, as widely believed, but around the transverse axis. The plane CPM rotated mainly around the longitudinal axis. The data obtained will be useful for prenatal diagnosis in the near future. Copyright © 2013 Wiley Periodicals, Inc.

Optimising Extinction of Conditioned Disgust.

PubMed

Bosman, Renske C; Borg, Charmaine; de Jong, Peter J

2016-01-01

Maladaptive disgust responses are tenacious and resistant to exposure-based interventions. In a similar vein, laboratory studies have shown that conditioned disgust is relatively insensitive to Conditioned Stimulus (CS)-only extinction procedures. The relatively strong resistance to extinction might be explained by disgust's adaptive function to motivate avoidance from contamination threats (pathogens) that cannot be readily detected and are invisible to the naked eye. Therefore, the mere visual presentation of unreinforced disgust eliciting stimuli might not be sufficient to correct a previously acquired threat value of the CS+. Following this, the current study tested whether the efficacy of CS-only exposure can be improved by providing additional safety information about the CS+. For the CSs we included two neutral items a pea soup and a sausage roll, whereas for the Unconditioned Stimulus (US) we used one video clip of a woman vomiting and a neutral one about glass blowing. The additional safety information was conveyed by allowing actual contact with the CS+ or by observing an actress eating the food items representing the CS+. When additional safety information was provided via allowing direct contact with the CS+, there was a relatively strong post-extinction increase in participants' willingness-to-eat the CS+. This beneficial effect was still evident at one-week follow up. Also self-reported disgust was lower at one-week follow up when additional safety information was provided. The current findings help explain why disgust is relatively insensitive to CS-only extinction procedures, and provide helpful starting points to improve interventions that are aimed to reduce distress in disgust-related psychopathology.

Changing facial phenotype in Cohen syndrome: towards clues for an earlier diagnosis.

PubMed

El Chehadeh-Djebbar, Salima; Blair, Edward; Holder-Espinasse, Muriel; Moncla, Anne; Frances, Anne-Marie; Rio, Marlène; Debray, François-Guillaume; Rump, Patrick; Masurel-Paulet, Alice; Gigot, Nadège; Callier, Patrick; Duplomb, Laurence; Aral, Bernard; Huet, Frédéric; Thauvin-Robinet, Christel; Faivre, Laurence

2013-07-01

Cohen syndrome (CS) is a rare autosomal recessive condition caused by mutations and/or large rearrangements in the VPS13B gene. CS clinical features, including developmental delay, the typical facial gestalt, chorioretinal dystrophy (CRD) and neutropenia, are well described. CS diagnosis is generally raised after school age, when visual disturbances lead to CRD diagnosis and to VPS13B gene testing. This relatively late diagnosis precludes accurate genetic counselling. The aim of this study was to analyse the evolution of CS facial features in the early period of life, particularly before school age (6 years), to find clues for an earlier diagnosis. Photographs of 17 patients with molecularly confirmed CS were analysed, from birth to preschool age. By comparing their facial phenotype when growing, we show that there are no special facial characteristics before 1 year. However, between 2 and 6 years, CS children already share common facial features such as a short neck, a square face with micrognathia and full cheeks, a hypotonic facial appearance, epicanthic folds, long ears with an everted upper part of the auricle and/or a prominent lobe, a relatively short philtrum, a small and open mouth with downturned corners, a thick lower lip and abnormal eye shapes. These early transient facial features evolve to typical CS facial features with aging. These observations emphasize the importance of ophthalmological tests and neutrophil count in children in preschool age presenting with developmental delay, hypotonia and the facial features we described here, for an earlier CS diagnosis.

One year follow-up of contrast sensitivity following conventional laser in situ keratomileusis and laser epithelial keratomileusis.

PubMed

Townley, Deirdre; Kirwan, Caitriona; O'Keefe, Michael

2012-02-01

To determine the effect of conventional laser in situ keratomileusis (LASIK) and laser epithelial keratomileusis (LASEK) for myopia on contrast sensitivity (CS) using the Pelli-Robson and Vector Vision CSV-1000E CS tests. A prospective, comparative study was conducted on 36 eyes of 36 patients with myopia undergoing LASIK (18 eyes) and LASEK (18 eyes). Surgery was performed using the Technolas 217z laser (Bausch & Lomb). CS was recorded preoperatively and at 3, 6 and 12 months postoperatively. No statistically significant difference was found in LogMAR uncorrected visual acuity post-LASIK (-0.02 ± 0.16) and LASEK (-0.04 ± 0.14). Using the Pelli-Robson, CS was significantly lower in the LASIK group 3 and 6 months postoperatively. No significant postoperative reduction in CS was observed in either treatment group. Using the CSV-1000E test, CS was significantly reduced post-LASIK at 3 (p = 0.05) and 6 (p = 0.05) cycles/degree under photopic conditions. No significant postoperative change occurred in the LASEK group under photopic or scotopic conditions. There was no significant difference in postoperative CS between the LASIK and LASEK groups at 3, 6, 12 or 18 cycles/degree using the CSV-1000E test. One year postoperatively, there was no difference in CS between both treatment groups using the Pelli-Robson and CSV-1000E tests. CS was reduced postoperatively in the LASIK group at the lower spatial frequencies under photopic conditions. No postoperative change was detected in CS following LASIK or LASEK using the Pelli-Robson test. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

GPU-accelerated compressed-sensing (CS) image reconstruction in chest digital tomosynthesis (CDT) using CUDA programming

NASA Astrophysics Data System (ADS)

Choi, Sunghoon; Lee, Haenghwa; Lee, Donghoon; Choi, Seungyeon; Shin, Jungwook; Jang, Woojin; Seo, Chang-Woo; Kim, Hee-Joung

2017-03-01

A compressed-sensing (CS) technique has been rapidly applied in medical imaging field for retrieving volumetric data from highly under-sampled projections. Among many variant forms, CS technique based on a total-variation (TV) regularization strategy shows fairly reasonable results in cone-beam geometry. In this study, we implemented the TV-based CS image reconstruction strategy in our prototype chest digital tomosynthesis (CDT) R/F system. Due to the iterative nature of time consuming processes in solving a cost function, we took advantage of parallel computing using graphics processing units (GPU) by the compute unified device architecture (CUDA) programming to accelerate our algorithm. In order to compare the algorithmic performance of our proposed CS algorithm, conventional filtered back-projection (FBP) and simultaneous algebraic reconstruction technique (SART) reconstruction schemes were also studied. The results indicated that the CS produced better contrast-to-noise ratios (CNRs) in the physical phantom images (Teflon region-of-interest) by factors of 3.91 and 1.93 than FBP and SART images, respectively. The resulted human chest phantom images including lung nodules with different diameters also showed better visual appearance in the CS images. Our proposed GPU-accelerated CS reconstruction scheme could produce volumetric data up to 80 times than CPU programming. Total elapsed time for producing 50 coronal planes with 1024×1024 image matrix using 41 projection views were 216.74 seconds for proposed CS algorithms on our GPU programming, which could match the clinically feasible time ( 3 min). Consequently, our results demonstrated that the proposed CS method showed a potential of additional dose reduction in digital tomosynthesis with reasonable image quality in a fast time.

The ventral visual pathway: an expanded neural framework for the processing of object quality.

PubMed

Kravitz, Dwight J; Saleem, Kadharbatcha S; Baker, Chris I; Ungerleider, Leslie G; Mishkin, Mortimer

2013-01-01

Since the original characterization of the ventral visual pathway, our knowledge of its neuroanatomy, functional properties, and extrinsic targets has grown considerably. Here we synthesize this recent evidence and propose that the ventral pathway is best understood as a recurrent occipitotemporal network containing neural representations of object quality both utilized and constrained by at least six distinct cortical and subcortical systems. Each system serves its own specialized behavioral, cognitive, or affective function, collectively providing the raison d'être for the ventral visual pathway. This expanded framework contrasts with the depiction of the ventral visual pathway as a largely serial staged hierarchy culminating in singular object representations and more parsimoniously incorporates attentional, contextual, and feedback effects. Published by Elsevier Ltd.

Comparing laser induced plasmas formed in diode and excimer pumped alkali lasers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markosyan, Aram H.

Here, lasing on the D 1 transition (6 2P 1/2 → 6 2S 1/2) of cesium can be reached in both diode and excimer pumped alkali lasers. The first uses D 2 transition (6 2S 1/2 → 6 2P 3/2) for pumping, whereas the second is pumped by photoexcitation of ground state Cs-Ar collisional pairs and subsequent dissociation of diatomic, electronically-excited CsAr molecules (excimers). Despite lasing on the same D 1 transition, differences in pumping schemes enables chemical pathways and characteristic timescales unique for each system. We investigate unavoidable plasma formation during operation of both systems side by side inmore » Ar/C 2H 6/Cs.« less

Comparing laser induced plasmas formed in diode and excimer pumped alkali lasers

DOE PAGES

Markosyan, Aram H.

2018-01-05

Here, lasing on the D 1 transition (6 2P 1/2 → 6 2S 1/2) of cesium can be reached in both diode and excimer pumped alkali lasers. The first uses D 2 transition (6 2S 1/2 → 6 2P 3/2) for pumping, whereas the second is pumped by photoexcitation of ground state Cs-Ar collisional pairs and subsequent dissociation of diatomic, electronically-excited CsAr molecules (excimers). Despite lasing on the same D 1 transition, differences in pumping schemes enables chemical pathways and characteristic timescales unique for each system. We investigate unavoidable plasma formation during operation of both systems side by side inmore » Ar/C 2H 6/Cs.« less

Comparing laser induced plasmas formed in diode and excimer pumped alkali lasers.

PubMed

Markosyan, Aram H

2018-01-08

Lasing on the D 1 transition (6 2 P 1/2 → 6 2 S 1/2 ) of cesium can be reached in both diode and excimer pumped alkali lasers. The first uses D 2 transition (6 2 S 1/2 → 6 2 P 3/2 ) for pumping, whereas the second is pumped by photoexcitation of ground state Cs-Ar collisional pairs and subsequent dissociation of diatomic, electronically-excited CsAr molecules (excimers). Despite lasing on the same D 1 transition, differences in pumping schemes enables chemical pathways and characteristic timescales unique for each system. We investigate unavoidable plasma formation during operation of both systems side by side in Ar/C 2 H 6 /Cs.

A procedure to observe context-induced renewal of pavlovian-conditioned alcohol-seeking behavior in rats.

PubMed

Maddux, Jean-Marie; Lacroix, Franca; Chaudhri, Nadia

2014-09-19

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

On the importance of electron impact processes in excimer-pumped alkali laser-induced plasmas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markosyan, Aram H.

We present that the excimer-pumped alkali laser (XPAL) system has recently been demonstrated in several different mixtures of alkali vapor and rare gas. Without special preventive measures, plasma formation during operation of XPAL is unavoidable. Some recent advancements in the availability of reliable data for electron impact collisions with atoms and molecules have enabled development of a complete reaction mechanism to investigate XPAL-induced plasmas. Here, we report on pathways leading to plasma formation in an Ar/C 2H 6/CsAr/C2H6/Cs XPAL sustained at different cell temperatures. We find that depending on the operating conditions, the contribution of electron impact processes can bemore » as little as bringing the excitation of Cs(P 2) states to higher level Cs** states, and can be as high as bringing Cs(P 2) excited states to a full ionization. Increasing the input pumping power or cell temperature, or decreasing the C 2H 6 mole fraction leads to electron impact processes dominating in plasma formation over the energy pooling mechanisms previously reported in literature.« less

On the importance of electron impact processes in excimer-pumped alkali laser-induced plasmas

DOE PAGES

Markosyan, Aram H.

2017-10-18

We present that the excimer-pumped alkali laser (XPAL) system has recently been demonstrated in several different mixtures of alkali vapor and rare gas. Without special preventive measures, plasma formation during operation of XPAL is unavoidable. Some recent advancements in the availability of reliable data for electron impact collisions with atoms and molecules have enabled development of a complete reaction mechanism to investigate XPAL-induced plasmas. Here, we report on pathways leading to plasma formation in an Ar/C 2H 6/CsAr/C2H6/Cs XPAL sustained at different cell temperatures. We find that depending on the operating conditions, the contribution of electron impact processes can bemore » as little as bringing the excitation of Cs(P 2) states to higher level Cs** states, and can be as high as bringing Cs(P 2) excited states to a full ionization. Increasing the input pumping power or cell temperature, or decreasing the C 2H 6 mole fraction leads to electron impact processes dominating in plasma formation over the energy pooling mechanisms previously reported in literature.« less

Intracellular Cs+ activates the PKA pathway, revealing a fast, reversible, Ca2+-dependent inactivation of L-type Ca2+ current.

PubMed

Brette, Fabien; Lacampagne, Alain; Sallé, Laurent; Findlay, Ian; Le Guennec, Jean-Yves

2003-08-01

Inactivation of the L-type Ca2+ current (ICaL) was studied in isolated guinea pig ventricular myocytes with different ionic solutions. Under basal conditions, ICaL of 82% of cells infused with Cs+-based intracellular solutions showed enhanced amplitude with multiphasic decay and diastolic depolarization-induced facilitation. The characteristics of ICaL in this population of cells were not due to contamination by other currents or an artifact. These phenomena were reduced by ryanodine, caffeine, cyclopiazonic acid, the protein kinase A inhibitor H-89, and the cAMP-dependent protein kinase inhibitor. Forskolin and isoproterenol increased ICaL by only approximately 60% in these cells. Cells infused with either N-methyl-d-glucamine or K+-based intracellular solutions did not show multiphasic decay or facilitation under basal conditions. Isoproterenol increased ICaL by approximately 200% in these cells. In conclusion, we show that multiphasic inactivation of ICaL is due to Ca2+-dependent inactivation that is reversible on a time scale of tens of milliseconds. Cs+ seems to activate the cAMP-dependent protein kinase pathway when used as a substitute for K+ in the pipette solution.

Diverse Distributions of Extraocular Opsins in Crustaceans, Cephalopods, and Fish.

PubMed

Kingston, Alexandra C N; Cronin, Thomas W

2016-11-01

Non-visual and extraocular photoreceptors are common among animals, but current understanding linking molecular pathways to physiological function of these receptors is lacking. Opsin diversity in extraocular tissues suggests that many putative extraocular photoreceptors utilize the "visual" phototransduction pathway-the same phototransduction pathway as photoreceptors within the retina dedicated to light detection for image sensing. Here, we provide a brief overview of the current understanding of non-visual and extraocular photoreceptors, and contribute a synopsis of several novel putative extraocular photoreceptors that use both visual and non-visual phototransduction pathways. Crayfish, cephalopods, and flat fish express opsins in diverse tissues, suggesting the presence of extraocular photoreceptors. In most cases, we find that these animals use the same phototransduction pathway that is utilized in the retinas for image-formation. However, we also find the presence of non-visual phototransduction components in the skin of flounders. Our evidence suggests that extraocular photoreceptors may employ a number of phototransduction pathways that do not appear to correlate with purpose or location of the photoreceptor. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Cigarette Smoke Upregulates PDE3 and PDE4 to Decrease cAMP in Airway Cells.

PubMed

Zuo, Haoxiao; Han, Bing; Poppinga, Wilfred J; Ringnalda, Lennard; Kistemaker, Loes E M; Halayko, Andrew J; Gosens, Reinoud; Nikolaev, Viacheslav O; Schmidt, Martina

2018-05-03

3', 5'-cyclic adenosine monophosphate (cAMP) is a central second messenger that broadly regulates cell function and can underpin pathophysiology. In chronic obstructive pulmonary disease (COPD), a lung disease primarily provoked by cigarette smoke (CS), the induction of cAMP-dependent pathways, via inhibition of hydrolyzing phosphodiesterases (PDEs), is a prime therapeutic strategy. Mechanisms that disrupt cAMP signaling in airway cells, in particular regulation of endogenous PDEs are poorly understood. We used a novel Förster resonance energy transfer (FRET) based cAMP biosensor in mouse in vivo, ex vivo precision cut lung slices (PCLS), and in human in vitro cell models to track the effects of CS exposure. Under fenoterol stimulated conditions, FRET responses to cilostamide were significantly increased in in vivo, ex vivo PCLS exposed to CS and in human airway smooth muscle cells exposed to CS extract. FRET signals to rolipram were only increased in the in vivo CS model. Under basal conditions, FRET responses to cilostamide and rolipram were significantly increased in in vivo, ex vivo PCLS exposed to CS. Elevated FRET signals to rolipram correlated with a protein upregulation of PDE4 subtypes. In ex vivo PCLS exposed to CS extract, rolipram reversed downregulation of ciliary beating frequency, whereas only cilostamide significantly increased airway relaxation of methacholine pre-contracted airways. We show that CS upregulates expression and activity of both PDE3 and PDE4, which regulate real-time cAMP dynamics. These mechanisms determine the availability of cAMP and can contribute to CS-induced pulmonary pathophysiology. This article is protected by copyright. All rights reserved.

Arctigenin Inhibits Osteoclast Differentiation and Function by Suppressing Both Calcineurin-Dependent and Osteoblastic Cell-Dependent NFATc1 Pathways

PubMed Central

Yamashita, Teruhito; Uehara, Shunsuke; Udagawa, Nobuyuki; Li, Feng; Kadota, Shigetoshi; Esumi, Hiroyasu; Kobayashi, Yasuhiro; Takahashi, Naoyuki

2014-01-01

Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM) cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA), a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the pit-forming activity of osteoclast-like cells cultured on dentin slices. These results suggest that arctigenin induces a dominant negative species of NFATc1, which inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways. PMID:24465763

Arctigenin inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.

PubMed

Yamashita, Teruhito; Uehara, Shunsuke; Udagawa, Nobuyuki; Li, Feng; Kadota, Shigetoshi; Esumi, Hiroyasu; Kobayashi, Yasuhiro; Takahashi, Naoyuki

2014-01-01

Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM) cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA), a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the pit-forming activity of osteoclast-like cells cultured on dentin slices. These results suggest that arctigenin induces a dominant negative species of NFATc1, which inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.

Emotional conditioning to masked stimuli and modulation of visuospatial attention.

PubMed

Beaver, John D; Mogg, Karin; Bradley, Brendan P

2005-03-01

Two studies investigated the effects of conditioning to masked stimuli on visuospatial attention. During the conditioning phase, masked snakes and spiders were paired with a burst of white noise, or paired with an innocuous tone, in the conditioned stimulus (CS)+ and CS- conditions, respectively. Attentional allocation to the CSs was then assessed with a visual probe task, in which the CSs were presented unmasked (Experiment 1) or both unmasked and masked (Experiment 2), together with fear-irrelevant control stimuli (flowers and mushrooms). In Experiment 1, participants preferentially allocated attention to CS+ relative to control stimuli. Experiment 2 suggested that this attentional bias depended on the perceived aversiveness of the unconditioned stimulus and did not require conscious recognition of the CSs during both acquisition and expression. Copyright 2005 APA, all rights reserved.

Functional Role of N- and C-Terminal Amino Acids in the Structural Subunits of Colonization Factor CS6 Expressed by Enterotoxigenic Escherichia coli

PubMed Central

Debnath, Anusuya; Sabui, Subrata; Wajima, Takeaki; Hamabata, Takashi; Banerjee, Rajat

2016-01-01

ABSTRACT CS6 is a common colonization factor expressed by enterotoxigenic Escherichia coli. It is a two-subunit protein consisting of CssA and CssB in an equal stoichiometry, assembled via the chaperone-usher pathway into an afimbrial, oligomeric assembly on the bacterial cell surface. A recent structural study has predicted the involvement of the N- and C-terminal regions of the CS6 subunits in its assembly. Here, we identified the functionally important residues in the N- and C-terminal regions of the CssA and CssB subunits during CS6 assembly by alanine scanning mutagenesis. Bacteria expressing mutant proteins were tested for binding with Caco-2 cells, and the results were analyzed with respect to the surface expression of mutant CS6. In this assay, many mutant proteins were not expressed on the surface while some showed reduced expression. It appeared that some, but not all, of the residues in both the N and C termini of CssA and CssB played an important role in the intermolecular interactions between these two structural subunits, as well as chaperone protein CssC. Our results demonstrated that T20, K25, F27, S36, Y143, and V147 were important for the stability of CssA, probably through interaction of CssC. We also found that I22, V29, and I33 of CssA and G154, Y156, L160, V162, F164, and Y165 of CssB were responsible for CssA-CssB intermolecular interactions. In addition, some of the hydrophobic residues in the C terminus of CssA and the N terminus of CssB were involved in the stabilization of higher-order complex formation. Overall, the results presented here might help in understanding the pathway used to assemble CS6 and predict its structure. IMPORTANCE Unlike most other colonization factors, CS6 is nonfimbrial, and in a sense, its subunit composition and assembly are also unique. Here we report that both the N- and C-terminal amino acid residues of CssA and CssB play a critical role in the intermolecular interactions between them and assembly proteins. We found mainly that alternate hydrophobic residues present in these motifs are essential for the interaction between the structural subunits, as well as the chaperone and usher assembly proteins. Our results indicate the involvement of the side chains of identified amino acids in CS6 assembly. This study adds a step toward understanding the interactions between structural subunits of CS6 and assembly proteins during CS6 biogenesis. PMID:26929298

[Efficacy of chondroitin sulphate in the treatment of elderly patients with gonarthrosis and coxarthrosis].

PubMed

Lazebnik, L B; Drozdov, V N

2005-01-01

To study chondroitin sulphate (CS) efficacy, tolerance and response duration in elderly patients with osteoarthrosis (OA) with consideration of OA duration and stage. A total of 97 patients aged 65-85 years with stage II-IV OA by Kellgren-Lawrence received CS treatment. The treatment efficacy was assessed by functional Lecken's index, pain intensity at walking and rest, general functional condition, need in nonsteroid anti-inflammatory (NSAI) drugs. Standardization was achieved with visual analogue scale (VAS). Positive effects (pain relief, better functional parameters, lower intake of NSAI drugs) were more pronounced and stable in patients with OA stage 1 and 2. In OA of stage 3 and 4, a beneficial effect of a 6-month CS course was unstable. Side effects were at the level of mean statistics. CS (structum) is recommended for treatment of OA stage 1-4 by Kellgren-Lawrence. Duration of the treatment depends on severity of x-ray symptoms of the disease.

Lung Cancer and Lung Injury: The Dual Role of Ceramide

PubMed Central

Goldkorn, Tzipora; Chung, Samuel; Filosto, Simone

2015-01-01

Sphingolipids play key roles in cancer, yet our current understanding of sphingolipid function in lung cancer is limited to a few key players. The best characterized of these are sphingosine-1-phoshate and ceramide which are described for their opposing roles in cell fate. However, because sphingolipids as a whole are readily interconverted by a complex enzymatic machinery, no single sphingolipid appears to have exactly one role. Instead, the roles of specific sphingolipids appear to be context specific as demonstrated by findings that ceramide-1-phosphate has both proliferative and apoptotic effects depending on its concentration. Therefore, we present herein several years of research on ceramide, a sphingolipid linked to apoptotic signaling, that is emerging in cancer research for its potential roles in proliferation and cell-to-cell communication via exosomes. Ceramide is a well-studied sphingolipid in both normal and pathological conditions ranging from skin development to lung cancer. Interestingly, several groups have previously reported its increased levels in emphysema patients who are smokers, a patient subpopulation greatly susceptible to lung cancer. However, the molecular mechanisms through which cigarette smoke (CS) and ceramide accumulation lead to lung cancer, non-small cell lung cancer (NSCLC) specifically, are unknown. Interestingly, recent studies clearly establish that two signaling pathways are activated during CS exposure in the lung airway. One centers on the activation of neutral sphingomyelinase2 (nSMase2), an enzyme that hydrolyzes sphingomyelin to ceramide. The other pathway focuses on the oncogenic EGF receptor (EGFR), which becomes aberrantly activated but not degraded, leading to prolonged proliferative signaling. Recent studies show that these two signaling pathways may actually converge and integrate. Specifically, Goldkorn et al. demonstrated that during CS exposure, EGFR is favorably co-localized in ceramide-enriched regions of the plasma membrane, proposing that nSMase2/ceramide plays a role in the aberrant EGFR activation, leading to augmented tumorigenic signaling. Moreover, new findings indicate that CS exposure may induce resistance to the tyrosine kinase inhibitors (TKIs), used for treatment of NSCLC, merely through posttranslational molecular alterations. Furthermore, structural anomalies of the CS-activated EGFR appear to be supported by the excess ceramide produced by the CS-activated nSMase2 in the plasma membrane of lung epithelial cells. We present in this chapter the progression of the sphingolipid field in lung cancer using ceramide as an example. However, many crucial questions remain to be answered regarding the role of sphingolipids in lung cancer because of the glut of promising observations. PMID:23563653

Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models

PubMed Central

Shen, Xiujin; Jiang, Hong; Ying, Meike; Xie, Zhoutao; Li, Xiayu; Wang, Haibing; Zhao, Jie; Lin, Chuan; Wang, Yucheng; Feng, Shi; Shen, Jia; Weng, Chunhua; Lin, Weiqiang; Wang, Huiping; Zhou, Qin; Bi, Yan; Li, Meng; Wang, Lingyan; Zhu, Tongyu; Huang, Xiaoru; Lan, Hui-Yao; Zhou, Jing; Chen, Jianghua

2016-01-01

Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway. PMID:27580845

Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet-fed rat.

PubMed

Han, Ying; Lin, Min; Wang, Xiaobin; Guo, Keke; Wang, Shanshan; Sun, Mengfei; Wang, Jiao; Han, Xiaoyu; Fu, Ting; Hu, Yang; Fu, Jihua

2015-03-01

Our previous study has demonstrated that long-term stress, known as chronic stress (CS), can aggravate nonalcoholic fatty liver disease in high-fat diet (HFD)-fed rat. In this study, we tried to figure out which lipid metabolic pathways were impacted by CS in the HFD-fed rat. Male Sprague-Dawley rats (6 weeks of age, n = 8 per group) were fed with either standard diet or HFD with or without CS exposure for 8 weeks. Hepatic lipidosis, biochemical, hormonal, and lipid profile markers in serum and liver, and enzymes involved in de novo lipogenesis (DNL) of fatty acids (FAs) and cholesterol, β-oxidation, FAs uptake, triglycerides synthesis, and very low-density lipoprotein (VLDL) assembly in the liver were detected. CS exposure reduced hepatic lipidosis but further elevated hepatic VLDL content with aggravated dyslipidemia in the HFD-fed rats. There was a synergism between CS and HFD on VLDL production and dyslipidemia. PCR and western blot assays showed that CS exposure significantly promoted hepatic VLDL assembly in rats, especially in the HFD-fed rats, while it had little impact on DNL, β-oxidation, FAs uptake, and triglycerides synthesis in the HFD-fed rats. This phenomenon was in accordance with elevated serum glucocorticoid level. The critical influence of CS exposure on hepatic lipid metabolism in the HFD-fed rats is VLDL assembly which might be regulated by glucocorticoid.

VisANT 3.0: new modules for pathway visualization, editing, prediction and construction.

PubMed

Hu, Zhenjun; Ng, David M; Yamada, Takuji; Chen, Chunnuan; Kawashima, Shuichi; Mellor, Joe; Linghu, Bolan; Kanehisa, Minoru; Stuart, Joshua M; DeLisi, Charles

2007-07-01

With the integration of the KEGG and Predictome databases as well as two search engines for coexpressed genes/proteins using data sets obtained from the Stanford Microarray Database (SMD) and Gene Expression Omnibus (GEO) database, VisANT 3.0 supports exploratory pathway analysis, which includes multi-scale visualization of multiple pathways, editing and annotating pathways using a KEGG compatible visual notation and visualization of expression data in the context of pathways. Expression levels are represented either by color intensity or by nodes with an embedded expression profile. Multiple experiments can be navigated or animated. Known KEGG pathways can be enriched by querying either coexpressed components of known pathway members or proteins with known physical interactions. Predicted pathways for genes/proteins with unknown functions can be inferred from coexpression or physical interaction data. Pathways produced in VisANT can be saved as computer-readable XML format (VisML), graphic images or high-resolution Scalable Vector Graphics (SVG). Pathways in the format of VisML can be securely shared within an interested group or published online using a simple Web link. VisANT is freely available at http://visant.bu.edu.

The ventral visual pathway: An expanded neural framework for the processing of object quality

PubMed Central

Kravitz, Dwight J.; Saleem, Kadharbatcha S.; Baker, Chris I.; Ungerleider, Leslie G.; Mishkin, Mortimer

2012-01-01

Since the original characterization of the ventral visual pathway our knowledge of its neuroanatomy, functional properties, and extrinsic targets has grown considerably. Here we synthesize this recent evidence and propose that the ventral pathway is best understood as a recurrent occipitotemporal network containing neural representations of object quality both utilized and constrained by at least six distinct cortical and subcortical systems. Each system serves its own specialized behavioral, cognitive, or affective function, collectively providing the raison d’etre for the ventral visual pathway. This expanded framework contrasts with the depiction of the ventral visual pathway as a largely serial staged hierarchy that culminates in singular object representations for utilization mainly by ventrolateral prefrontal cortex and, more parsimoniously than this account, incorporates attentional, contextual, and feedback effects. PMID:23265839

Voluntary exercise during extinction of auditory fear conditioning reduces the relapse of fear associated with potentiated activity of striatal direct pathway neurons

PubMed Central

Mika, Agnieszka; Bouchet, Courtney A.; Bunker, Preston; Hellwinkel, Justin E.; Spence, Katie G.; Day, Heidi E.W.; Campeau, Serge; Fleshner, Monika

2015-01-01

Relapse of previously extinguished fear presents a significant, pervasive obstacle to the successful long-term treatment of anxiety and trauma-related disorders. Thus, identification of a novel means to enhance fear extinction to stand the passage of time and generalize across contexts is of the utmost importance. Acute bouts of exercise can be used as inexpensive, noninvasive treatment strategies to reduce anxiety, and have been shown to enhance memory for extinction when performed in close temporal proximity to the extinction session. However, it is unclear whether acute exercise can be used to prevent relapse of fear, and the neural mechanisms underlying this potential effect are unknown. The current study therefore examined whether acute exercise during extinction of auditory fear can protect against the later relapse of fear. Male, F344 rats lacking an extended history of wheel running were conditioned to fear a tone CS and subsequently extinguished within either a freely mobile running wheel, a locked wheel, or a control context lacking a wheel. Rats exposed to fear extinction within a freely mobile wheel ran during fear extinction, and demonstrated reduced fear as well as attenuated corticosterone levels during re-exposure to the extinguished CS during the relapse test in a novel context 1 week later. Examination of cfos mRNA patterns elicited by re-exposure to the extinguished CS during the relapse test revealed that acute exercise during extinction decreased activation of brain circuits classically involved in driving fear expression and interestingly, increased activity within neurons of the direct striatal pathway involved in reward signaling. These data suggest that exercise during extinction reduces relapse through a mechanism involving the direct pathway of the striatum. It is suggested that a positive affective state could become associated with the CS during exercise during extinction, thus resulting in a relapse-resistant extinction memory. PMID:26454156

Voluntary exercise during extinction of auditory fear conditioning reduces the relapse of fear associated with potentiated activity of striatal direct pathway neurons.

PubMed

Mika, Agnieszka; Bouchet, Courtney A; Bunker, Preston; Hellwinkel, Justin E; Spence, Katie G; Day, Heidi E W; Campeau, Serge; Fleshner, Monika; Greenwood, Benjamin N

2015-11-01

Relapse of previously extinguished fear presents a significant, pervasive obstacle to the successful long-term treatment of anxiety and trauma-related disorders. Thus, identification of a novel means to enhance fear extinction to stand the passage of time and generalize across contexts is of the utmost importance. Acute bouts of exercise can be used as inexpensive, noninvasive treatment strategies to reduce anxiety, and have been shown to enhance memory for extinction when performed in close temporal proximity to the extinction session. However, it is unclear whether acute exercise can be used to prevent relapse of fear, and the neural mechanisms underlying this potential effect are unknown. The current study therefore examined whether acute exercise during extinction of auditory fear can protect against the later relapse of fear. Male F344 rats lacking an extended history of wheel running were conditioned to fear a tone CS and subsequently extinguished within either a freely mobile running wheel, a locked wheel, or a control context lacking a wheel. Rats exposed to fear extinction within a freely mobile wheel ran during fear extinction, and demonstrated reduced fear as well as attenuated corticosterone levels during re-exposure to the extinguished CS during the relapse test in a novel context 1week later. Examination of cfos mRNA patterns elicited by re-exposure to the extinguished CS during the relapse test revealed that acute exercise during extinction decreased activation of brain circuits classically involved in driving fear expression and interestingly, increased activity within neurons of the direct striatal pathway involved in reward signaling. These data suggest that exercise during extinction reduces relapse through a mechanism involving the direct pathway of the striatum. It is suggested that a positive affective state could become associated with the CS during exercise during extinction, thus resulting in a relapse-resistant extinction memory. Copyright © 2015 Elsevier Inc. All rights reserved.

Entourage: Visualizing Relationships between Biological Pathways using Contextual Subsets

PubMed Central

Lex, Alexander; Partl, Christian; Kalkofen, Denis; Streit, Marc; Gratzl, Samuel; Wassermann, Anne Mai; Schmalstieg, Dieter; Pfister, Hanspeter

2014-01-01

Biological pathway maps are highly relevant tools for many tasks in molecular biology. They reduce the complexity of the overall biological network by partitioning it into smaller manageable parts. While this reduction of complexity is their biggest strength, it is, at the same time, their biggest weakness. By removing what is deemed not important for the primary function of the pathway, biologists lose the ability to follow and understand cross-talks between pathways. Considering these cross-talks is, however, critical in many analysis scenarios, such as judging effects of drugs. In this paper we introduce Entourage, a novel visualization technique that provides contextual information lost due to the artificial partitioning of the biological network, but at the same time limits the presented information to what is relevant to the analyst’s task. We use one pathway map as the focus of an analysis and allow a larger set of contextual pathways. For these context pathways we only show the contextual subsets, i.e., the parts of the graph that are relevant to a selection. Entourage suggests related pathways based on similarities and highlights parts of a pathway that are interesting in terms of mapped experimental data. We visualize interdependencies between pathways using stubs of visual links, which we found effective yet not obtrusive. By combining this approach with visualization of experimental data, we can provide domain experts with a highly valuable tool. We demonstrate the utility of Entourage with case studies conducted with a biochemist who researches the effects of drugs on pathways. We show that the technique is well suited to investigate interdependencies between pathways and to analyze, understand, and predict the effect that drugs have on different cell types. Fig. 1Entourage showing the Glioma pathway in detail and contextual information of multiple related pathways. PMID:24051820

Fine-grained temporal coding of visually-similar categories in the ventral visual pathway and prefrontal cortex

PubMed Central

Xu, Yang; D'Lauro, Christopher; Pyles, John A.; Kass, Robert E.; Tarr, Michael J.

2013-01-01

Humans are remarkably proficient at categorizing visually-similar objects. To better understand the cortical basis of this categorization process, we used magnetoencephalography (MEG) to record neural activity while participants learned–with feedback–to discriminate two highly-similar, novel visual categories. We hypothesized that although prefrontal regions would mediate early category learning, this role would diminish with increasing category familiarity and that regions within the ventral visual pathway would come to play a more prominent role in encoding category-relevant information as learning progressed. Early in learning we observed some degree of categorical discriminability and predictability in both prefrontal cortex and the ventral visual pathway. Predictability improved significantly above chance in the ventral visual pathway over the course of learning with the left inferior temporal and fusiform gyri showing the greatest improvement in predictability between 150 and 250 ms (M200) during category learning. In contrast, there was no comparable increase in discriminability in prefrontal cortex with the only significant post-learning effect being a decrease in predictability in the inferior frontal gyrus between 250 and 350 ms (M300). Thus, the ventral visual pathway appears to encode learned visual categories over the long term. At the same time these results add to our understanding of the cortical origins of previously reported signature temporal components associated with perceptual learning. PMID:24146656

Compromised Integrity of Central Visual Pathways in Patients With Macular Degeneration.

PubMed

Malania, Maka; Konrad, Julia; Jägle, Herbert; Werner, John S; Greenlee, Mark W

2017-06-01

Macular degeneration (MD) affects the central retina and leads to gradual loss of foveal vision. Although, photoreceptors are primarily affected in MD, the retinal nerve fiber layer (RNFL) and central visual pathways may also be altered subsequent to photoreceptor degeneration. Here we investigate whether retinal damage caused by MD alters microstructural properties of visual pathways using diffusion-weighted magnetic resonance imaging. Six MD patients and six healthy control subjects participated in the study. Retinal images were obtained by spectral-domain optical coherence tomography (SD-OCT). Diffusion tensor images (DTI) and high-resolution T1-weighted structural images were collected for each subject. We used diffusion-based tensor modeling and probabilistic fiber tractography to identify the optic tract (OT) and optic radiations (OR), as well as nonvisual pathways (corticospinal tract and anterior fibers of corpus callosum). Fractional anisotropy (FA) and axial and radial diffusivity values (AD, RD) were calculated along the nonvisual and visual pathways. Measurement of RNFL thickness reveals that the temporal circumpapillary retinal nerve fiber layer was significantly thinner in eyes with macular degeneration than normal. While we did not find significant differences in diffusion properties in nonvisual pathways, patients showed significant changes in diffusion scalars (FA, RD, and AD) both in OT and OR. The results indicate that the RNFL and the white matter of the visual pathways are significantly altered in MD patients. Damage to the photoreceptors in MD leads to atrophy of the ganglion cell axons and to corresponding changes in microstructural properties of central visual pathways.

A multi-pathway hypothesis for human visual fear signaling

PubMed Central

Silverstein, David N.; Ingvar, Martin

2015-01-01

A hypothesis is proposed for five visual fear signaling pathways in humans, based on an analysis of anatomical connectivity from primate studies and human functional connectvity and tractography from brain imaging studies. Earlier work has identified possible subcortical and cortical fear pathways known as the “low road” and “high road,” which arrive at the amygdala independently. In addition to a subcortical pathway, we propose four cortical signaling pathways in humans along the visual ventral stream. All four of these traverse through the LGN to the visual cortex (VC) and branching off at the inferior temporal area, with one projection directly to the amygdala; another traversing the orbitofrontal cortex; and two others passing through the parietal and then prefrontal cortex, one excitatory pathway via the ventral-medial area and one regulatory pathway via the ventral-lateral area. These pathways have progressively longer propagation latencies and may have progressively evolved with brain development to take advantage of higher-level processing. Using the anatomical path lengths and latency estimates for each of these five pathways, predictions are made for the relative processing times at selective ROIs and arrival at the amygdala, based on the presentation of a fear-relevant visual stimulus. Partial verification of the temporal dynamics of this hypothesis might be accomplished using experimental MEG analysis. Possible experimental protocols are suggested. PMID:26379513

Combined electric and pressure cuff pain stimuli for assessing conditioning pain modulation (CPM).

PubMed

Tsukamoto, M; Petersen, K K; Mørch, C D; Arendt-Nielsen, L

2017-12-29

Aims Traditionally, conditioning pain modulation (CPM) can be assessed by applying a test stimulus (TS) before and after application of a conditioning stimulus (CS), which is normally applied extra-segmental. Currently, no studies have attempted to apply the TS and CS to the same site using different stimuli modalities. The aim of this study was to evaluate electrical TS and cuff pressure CS applied to the same experimental site for studying CPM. Methods 20 male volunteers participated in this study, which consisted of stimulations applied by a cuff-algometer (NociTech and Aalborg University, Denmark) and current stimulator (Digitimer DS5, UK), through two Ag/AgCl electrodes (Ambu® Neuroline 700, Denmark). The cuff was wrapped around the lower leg and stimulation electrodes were placed under the cuff and to the same location on the contralateral leg. Electrical TS were applied to the non-dominant leg with or without cuff pressure CS on the dominant (CS1) or the same (non-dominant) leg (CS2, electrode under cuff). The subjects were instructed to rate the electrical evoked pain intensity on a 10-cm continuous visual analog scale (VAS, "0" represented "no pain", and "10" represented "maximal pain"). The pain detection threshold (PDT) was defined as "1" on the VAS scale. Results There was no significant deference in PDT for neither CS1 nor CS2. A median split subanalysis on CPM-responders versus CPM-nonresponders to the TS + CS1 combination. Using this grouping, there was significant increase in PDT when comparing TS to TS + CS1 or TS + CS2 (4.0 mA vs 5.6 mA; P < 0.05, 4.0 mA vs 5.1 mA; P < 0.05). Conclusions The study indicates that CPM can be evoked in a subgroup of subjects by applying the electrical test stimulus and cuff pressure conditioning stimuli to the same experimental site.

Altered Pain Perception and Fear-Learning Deficits in Subjects With Posttraumatic Stress Disorder.

PubMed

Jenewein, Josef; Erni, Jeannine; Moergeli, Hanspeter; Grillon, Christian; Schumacher, Sonja; Mueller-Pfeiffer, Christoph; Hassanpour, Katayun; Seiler, Annina; Wittmann, Lutz; Schnyder, Ulrich; Hasler, Gregor

2016-12-01

There is growing evidence that fear-learning abnormalities are involved in the development of posttraumatic stress disorder (PTSD) and chronic pain. More than 50% of PTSD patients suffer from chronic pain. This study aimed to examine the role of fear-learning deficits in the link between pain perception and PTSD. We included 19 subjects with PTSD and 21 age- and sex-matched healthy control subjects in a fear-conditioning experiment. The conditioned stimulus (CS) consisted of visual signs flashed upon a screen in front of each subject. The unconditioned stimulus was either a low or high temperature impulse delivered through a thermal contact thermode on the subjects' hand. A designation of 'CS-' was assigned to CS always followed by nonpainful low-temperature stimuli; a designation of 'CS+' was given to CS that were randomly followed by either a low or a more painful high temperature. Skin conductance was used as a physiological marker of fear. In healthy control subjects, CS+ induced more fear than CS-, and a low-temperature stimulus induced less subjective pain after CS- than after CS+. PTSD subjects failed to demonstrate such adaptive conditioning. Fear ratings after CS presentation were significantly higher in the PTSD group than in the control group. There were significant interaction effects between group and the type of CS on fear and pain ratings. Fear-learning deficits are a potentially promising, specific psychopathological factor in altered pain perception associated with PTSD. Deficits in safety learning may increase fear and, consequently, pain sensations. These findings may contribute to elucidating the pathogenesis behind the highly prevalent comorbidity that exists between PTSD and pain disorders, and to developing new treatments. This study provides new insights into the pathogenesis of chronic pain in patients with PTSD. The findings may help to develop new treatment strategies for this highly prevalent comorbidity in PTSD. Copyright © 2016 American Pain Society. All rights reserved.

Effects of visual attention on chromatic and achromatic detection sensitivities.

PubMed

Uchikawa, Keiji; Sato, Masayuki; Kuwamura, Keiko

2014-05-01

Visual attention has a significant effect on various visual functions, such as response time, detection and discrimination sensitivity, and color appearance. It has been suggested that visual attention may affect visual functions in the early visual pathways. In this study we examined selective effects of visual attention on sensitivities of the chromatic and achromatic pathways to clarify whether visual attention modifies responses in the early visual system. We used a dual task paradigm in which the observer detected a peripheral test stimulus presented at 4 deg eccentricities while the observer concurrently carried out an attention task in the central visual field. In experiment 1, it was confirmed that peripheral spectral sensitivities were reduced more for short and long wavelengths than for middle wavelengths with the central attention task so that the spectral sensitivity function changed its shape by visual attention. This indicated that visual attention affected the chromatic response more strongly than the achromatic response. In experiment 2 it was obtained that the detection thresholds increased in greater degrees in the red-green and yellow-blue chromatic directions than in the white-black achromatic direction in the dual task condition. In experiment 3 we showed that the peripheral threshold elevations depended on the combination of color-directions of the central and peripheral stimuli. Since the chromatic and achromatic responses were separately processed in the early visual pathways, the present results provided additional evidence that visual attention affects responses in the early visual pathways.

Contingency Awareness Shapes Acquisition and Extinction of Emotional Responses in a Conditioning Model of Pain-Related Fear

PubMed Central

Labrenz, Franziska; Icenhour, Adriane; Benson, Sven; Elsenbruch, Sigrid

2015-01-01

As a fundamental learning process, fear conditioning promotes the formation of associations between predictive cues and biologically significant signals. In its application to pain, conditioning may provide important insight into mechanisms underlying pain-related fear, although knowledge especially in interoceptive pain paradigms remains scarce. Furthermore, while the influence of contingency awareness on excitatory learning is subject of ongoing debate, its role in pain-related acquisition is poorly understood and essentially unknown regarding extinction as inhibitory learning. Therefore, we addressed the impact of contingency awareness on learned emotional responses to pain- and safety-predictive cues in a combined dataset of two pain-related conditioning studies. In total, 75 healthy participants underwent differential fear acquisition, during which rectal distensions as interoceptive unconditioned stimuli (US) were repeatedly paired with a predictive visual cue (conditioned stimulus; CS+) while another cue (CS−) was presented unpaired. During extinction, both CS were presented without US. CS valence, indicating learned emotional responses, and CS-US contingencies were assessed on visual analog scales (VAS). Based on an integrative measure of contingency accuracy, a median-split was performed to compare groups with low vs. high contingency accuracy regarding learned emotional responses. To investigate predictive value of contingency accuracy, regression analyses were conducted. Highly accurate individuals revealed more pronounced negative emotional responses to CS+ and increased positive responses to CS− when compared to participants with low contingency accuracy. Following extinction, highly accurate individuals had fully extinguished pain-predictive cue properties, while exhibiting persistent positive emotional responses to safety signals. In contrast, individuals with low accuracy revealed equally positive emotional responses to both, CS+ and CS−. Contingency accuracy predicted variance in the formation of positive responses to safety cues while no predictive value was found for danger cues following acquisition and for neither cue following extinction. Our findings underscore specific roles of learned danger and safety in pain-related acquisition and extinction. Contingency accuracy appears to distinctly impact learned emotional responses to safety and danger cues, supporting aversive learning to occur independently from CS-US awareness. The interplay of cognitive and emotional factors in shaping excitatory and inhibitory pain-related learning may contribute to altered pain processing, underscoring its clinical relevance in chronic pain. PMID:26640433

Hybrid composite membranes of chitosan/sulfonated polyaniline/silica as polymer electrolyte membrane for fuel cells.

PubMed

Vijayakumar, Vijayalekshmi; Khastgir, Dipak

2018-01-01

A series of novel ionic cross-linked chitosan (CS) based hybrid nanocomposites were prepared by using polyaniline/nano silica (PAni/SiO 2 ) as inorganic filler and sulfuric acid as an ionic cross-linking agent. The CS-PAni/SiO 2 nanocomposites show enhanced mechanical properties and improved oxidative stabilities. These nanocomposites can be effectively used as environmental friendly proton exchange membranes. Incorporation of PAni/SiO 2 into CS matrix enhances water uptake and facilitates the phase separation which enables the formation of hydrophilic domains and improves the proton transport. Moreover, the doped polyaniline also provides some additional pathways for proton conduction. The membrane containing 3wt% loading of PAni/SiO 2 in chitosan (CS-PAni/SiO 2 -3) exhibits high proton conductivity at 80°C (8.39×10 -3 Scm -1 ) in fully hydrated state due to its excellent water retention properties. Moreover, methanol permeability of the ionic cross-linked CS-PAni/SiO 2 nanocomposite membranes significantly reduces with the addition of PAni/SiO 2 nano particles. The CS-PAni/SiO 2 -3 composite membrane displays the best overall performance as a polymer electrolyte membrane. Copyright © 2017 Elsevier Ltd. All rights reserved.

Salt stress encourages proline accumulation by regulating proline biosynthesis and degradation in Jerusalem artichoke plantlets.

PubMed

Huang, Zengrong; Zhao, Long; Chen, Dandan; Liang, Mingxiang; Liu, Zhaopu; Shao, Hongbo; Long, Xiaohua

2013-01-01

Proline accumulation is an important mechanism for osmotic regulation under salt stress. In this study, we evaluated proline accumulation profiles in roots, stems and leaves of Jerusalem artichoke (Helianthus tuberosus L.) plantlets under NaCl stress. We also examined HtP5CS, HtOAT and HtPDH enzyme activities and gene expression patterns of putative HtP5CS1, HtP5CS2, HtOAT, HtPDH1, and HtPDH2 genes. The objective of our study was to characterize the proline regulation mechanisms of Jerusalem artichoke, a moderately salt tolerant species, under NaCl stress. Jerusalem artichoke plantlets were observed to accumulate proline in roots, stems and leaves during salt stress. HtP5CS enzyme activities were increased under NaCl stress, while HtOAT and HtPDH activities generally repressed. Transcript levels of HtP5CS2 increased while transcript levels of HtOAT, HtPDH1 and HtPDH2 generally decreased in response to NaCl stress. Our results supports that for Jerusalem artichoke, proline synthesis under salt stress is mainly through the Glu pathway, and HtP5CS2 is predominant in this process while HtOAT plays a less important role. Both HtPDH genes may function in proline degradation.

Modulation of Complex-Spike Duration and Probability during Cerebellar Motor Learning in Visually Guided Smooth-Pursuit Eye Movements of Monkeys

PubMed Central

2017-01-01

Abstract Activation of an inferior olivary neuron powerfully excites Purkinje cells via its climbing fiber input and triggers a characteristic high-frequency burst, known as the complex spike (CS). The theory of cerebellar learning postulates that the CS induces long-lasting depression of the strength of synapses from active parallel fibers onto Purkinje cells, and that synaptic depression leads to changes in behavior. Prior reports showed that a CS on one learning trial is linked to a properly timed depression of simple spikes on the subsequent trial, as well as a learned change in pursuit eye movement. Further, the duration of a CS is a graded instruction for single-trial plasticity and behavioral learning. We now show across multiple learning paradigms that both the probability and duration of CS responses are correlated with the magnitudes of neural and behavioral learning in awake behaving monkeys. When the direction of the instruction for learning repeatedly was in the same direction or alternated directions, the duration and probability of CS responses decreased over a learning block along with the magnitude of trial-over-trial neural learning. When the direction of the instruction was randomized, CS duration, CS probability, and neural and behavioral learning remained stable across time. In contrast to depression, potentiation of simple-spike firing rate for ON-direction learning instructions follows a longer time course and plays a larger role as depression wanes. Computational analysis provides a model that accounts fully for the detailed statistics of a complex set of data. PMID:28698888

Neural circuitry of abdominal pain-related fear learning and reinstatement in irritable bowel syndrome.

PubMed

Icenhour, A; Langhorst, J; Benson, S; Schlamann, M; Hampel, S; Engler, H; Forsting, M; Elsenbruch, S

2015-01-01

Altered pain anticipation likely contributes to disturbed central pain processing in chronic pain conditions like irritable bowel syndrome (IBS), but the learning processes shaping the expectation of pain remain poorly understood. We assessed the neural circuitry mediating the formation, extinction, and reactivation of abdominal pain-related memories in IBS patients compared to healthy controls (HC) in a differential fear conditioning paradigm. During fear acquisition, predictive visual cues (CS(+)) were paired with rectal distensions (US), while control cues (CS(-)) were presented unpaired. During extinction, only CSs were presented. Subsequently, memory reactivation was assessed with a reinstatement procedure involving unexpected USs. Using functional magnetic resonance imaging, group differences in neural activation to CS(+) vs CS(-) were analyzed, along with skin conductance responses (SCR), CS valence, CS-US contingency, state anxiety, salivary cortisol, and alpha-amylase activity. The contribution of anxiety symptoms was addressed in covariance analyses. Fear acquisition was altered in IBS, as indicated by more accurate contingency awareness, greater CS-related valence change, and enhanced CS(+)-induced differential activation of prefrontal cortex and amygdala. IBS patients further revealed enhanced differential cingulate activation during extinction and greater differential hippocampal activation during reinstatement. Anxiety affected neural responses during memory formation and reinstatement. Abdominal pain-related fear learning and memory processes are altered in IBS, mediated by amygdala, cingulate cortex, prefrontal areas, and hippocampus. Enhanced reinstatement may contribute to hypervigilance and central pain amplification, especially in anxious patients. Preventing a 'relapse' of learned fear utilizing extinction-based interventions may be a promising treatment goal in IBS. © 2014 John Wiley & Sons Ltd.

Visual acuity, contrast sensitivity, and range performance with compressed motion video

NASA Astrophysics Data System (ADS)

Bijl, Piet; de Vries, Sjoerd C.

2010-10-01

Video of visual acuity (VA) and contrast sensitivity (CS) test charts in a complex background was recorded using a CCD color camera mounted on a computer-controlled tripod and was fed into real-time MPEG-2 compression/decompression equipment. The test charts were based on the triangle orientation discrimination (TOD) test method and contained triangle test patterns of different sizes and contrasts in four possible orientations. In a perception experiment, observers judged the orientation of the triangles in order to determine VA and CS thresholds at the 75% correct level. Three camera velocities (0, 1.0, and 2.0 deg/s, or 0, 4.1, and 8.1 pixels/frame) and four compression rates (no compression, 4 Mb/s, 2 Mb/s, and 1 Mb/s) were used. VA is shown to be rather robust to any combination of motion and compression. CS, however, dramatically decreases when motion is combined with high compression ratios. The measured thresholds were fed into the TOD target acquisition model to predict the effect of motion and compression on acquisition ranges for tactical military vehicles. The effect of compression on static performance is limited but strong with motion video. The data suggest that with the MPEG2 algorithm, the emphasis is on the preservation of image detail at the cost of contrast loss.

Effect of Grade I and II Intraventricular Hemorrhage on Visuocortical Function in Very Low Birth Weight Infants

PubMed Central

Madan, Ashima; Norcia, Anthony M.; Hou, Chuan; Pettet, Mark W.; Good, William V.

2015-01-01

The neurological outcome for infants with Grade I/II intraventricular hemorrhage (IVH) is debated. The aim of this study was to determine whether very low birth weight infants (VLBW, < 1500 g) with Grade I /II (IVH) have altered visuocortical activity compared with infants with no IVH. We assessed the quantitative swept parameter Visual Evoked Potential (sVEP) responses evoked by three different visual stimuli. Data from 52 VLBW infants were compared with data from 13 infants with Grade I or II IVH, enrolled at 5 – 7 months corrected age. Acuity thresholds and suprathreshold response amplitudes were compared. Grating Acuity (GA), Contrast Sensitivity (CS) and Vernier Acuity (VA) were each worse in the Grade I/ II IVH compared with the no IVH groups (8.24 cpd in IVH group vs 13.07 cpd in no IVH group for GA; 1.44% vs 1.18% for CS and 1.55 arcmin vs 0.58 arcmin for VA). The slopes of the response amplitude for CS and VA were significantly lower in IVH infants. The spatial frequency tuning function was shifted downward on the spatial frequency axis, without a change in slope. These results indicate that Grade I/II IVH are associated with deleterious effects on cortical vision development and function. PMID:22371027

Ontology-driven data integration and visualization for exploring regional geologic time and paleontological information

NASA Astrophysics Data System (ADS)

Wang, Chengbin; Ma, Xiaogang; Chen, Jianguo

2018-06-01

Initiatives of open data promote the online publication and sharing of large amounts of geologic data. How to retrieve information and discover knowledge from the big data is an ongoing challenge. In this paper, we developed an ontology-driven data integration and visualization pilot system for exploring information of regional geologic time, paleontology, and fundamental geology. The pilot system (http://www2.cs.uidaho.edu/%7Emax/gts/)

[The Cotard syndrome in schizophrenic disorders].

PubMed

Stompe, Thomas; Schanda, Hans

2013-01-01

The Cotard-Syndrome (CS), the belief of being dead, was described for the first time in 1880. Since then it met the interest not only of psychopathologists but also of philosophers. With a few exceptions, the literature is mainly restricted to case reports of anxious-depressive, demented or paranoid patients. It was the aim of our study to investigate the prevalence and the psychopathological context of the CS. We analyzed the Austrian data (N = 346) of the International Study of Psychotic Symptoms in Schizophrenia. A CS could be diagnosed in three cases (0.87%). In all of them, CS developed on the basis of nihilistic-hypochondriac delusions and a progressive loss of energy. Two patients bridged the logical inconsistencies between obviously being alive and the belief of being dead by visual illusions, the third patient, however, by locating himself in an intermediate region between this world and the afterworld. On the one hand the CS can be considered as a special manifestation of the topic of death in schizophrenic delusions, on the other as a nihilistic delusional identity. Without doubt, this uncommon and bizarre psychotic phenomenon will be an object of interest for general psychopathology as well as for the philosophy of mind also in future.

Cockayne syndrome: Clinical features, model systems and pathways

PubMed Central

Karikkineth, Ajoy C.; Scheibye-Knudsen, Morten; Fivenson, Elayne; Croteau, Deborah L.; Bohr, Vilhelm A.

2016-01-01

Cockayne syndrome (CS) is a disorder characterized by a variety of clinical features including cachectic dwarfism, severe neurological manifestations including microcephaly and cognitive deficits, pigmentary retinopathy, cataracts, sensorineural deafness, and ambulatory and feeding difficulties, leading to death by 12 years of age on average. It is an autosomal recessive disorder, with a prevalence of approximately 2.5 per million. There are several phenotypes (1, 2 and 3) and complementation groups (CSA and CSB), and overlaps with xeroderma pigmentosum (XP). It has been considered a progeria, and many of the clinical features resemble accelerated aging. As such, the study of CS affords an opportunity to better understand the underlying mechanisms of aging. The molecular basis of CS has traditionally been considered to be due to defects in transcription and transcription-coupled nucleotide excision repair (TC-NER). However, recent work suggests that defects in base excision DNA repair and mitochondrial functions may also play key roles. This opens up the possibility of molecular interventions in CS, and by extrapolation, possibly in aging. PMID:27507608

Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A.

PubMed

Antunes, Ricardo F; Brandão, Cláudia; Carvalho, Gonçalo; Girão, Cristina; Arosa, Fernando A

2009-10-01

Red blood cells (RBC) have emerged as a novel regulatory cell type endowed with bioactivities toward activated human T cells. Herein we show that the RBC bioactivities act on intracellular pathways initiated by T cell receptor (TCR)-dependent and -independent stimuli,including IL-2, IL-15, and the mixture of phorbol dibutyrate and ionomycin. The RBC bioactivities preserve the antioxidant status and are capable of rescuing activated T cells from cell death induced by serum deprivation. They are not mediated by glycosylphosphatidylinositol-linked receptors or sialic acids, and kinetic studies revealed that they hasten the entrance into the cell cycle. By using cyclosporine A (CsA) and rapamycin (Rapa) we show that the RBC bioactivities are calcineurin-dependent. Thus, treatment of T cells with CsA, but not Rapa, impaired RBC bioactivities, and preincubation of RBC with CsA completely abolished their bioactivities. We have demonstrated that RBC carry out bioactivities that are sensitive to CsA.

Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse.

PubMed

Tomie, Arthur; Grimes, Kathryn L; Pohorecky, Larissa A

2008-06-01

Drug abuse researchers have noted striking similarities between behaviors elicited by Pavlovian sign-tracking procedures and prominent symptoms of drug abuse. In Pavlovian sign-tracking procedures, repeated paired presentations of a small object (conditioned stimulus, CS) with a reward (unconditioned stimulus, US) elicits a conditioned response (CR) that typically consists of approaching the CS, contacting the CS, and expressing consummatory responses at the CS. Sign-tracking CR performance is poorly controlled and exhibits spontaneous recovery and long-term retention, effects that resemble relapse. Sign-tracking resembles psychomotor activation, a syndrome of behavioral responses evoked by addictive drugs, and the effects of sign-tracking on corticosterone levels and activation of dopamine pathways resemble the neurobiological effects of abused drugs. Finally, the neurobiological profile of individuals susceptible to sign-tracking resembles the pathophysiological profile of vulnerability to drug abuse, and vulnerability to sign-tracking predicts vulnerability to impulsive responding and alcohol self-administration. Implications of sign-tracking for models of drug addiction are considered.

Perinatal features of the RASopathies: Noonan syndrome, cardiofaciocutaneous syndrome and Costello syndrome.

PubMed

Myers, Angela; Bernstein, Jonathan A; Brennan, Marie-Luise; Curry, Cynthia; Esplin, Edward D; Fisher, Jamie; Homeyer, Margaret; Manning, Melanie A; Muller, Eric A; Niemi, Anna-Kaisa; Seaver, Laurie H; Hintz, Susan R; Hudgins, Louanne

2014-11-01

The RASopathies are a family of developmental disorders caused by heritable defects of the RAS/MAPK signaling pathway. While the postnatal presentation of this group of disorders is well known, the prenatal and neonatal findings are less widely recognized. We report on the perinatal presentation of 10 patients with Noonan syndrome (NS), nine with Cardiofaciocutaneous syndrome (CFCS) and three with Costello syndrome (CS), in conjunction with the results of a comprehensive literature review. The majority of perinatal findings in NS, CS, and CFCS are shared: polyhydramnios; prematurity; lymphatic dysplasia; macrosomia; relative macrocephaly; respiratory distress; hypotonia, as well as cardiac and renal anomalies. In contrast, fetal arrhythmia and neonatal hypoglycemia are relatively specific to CS. NS, CS, and CFCS should all be considered as a possible diagnosis in pregnancies with a normal karyotype and ultrasound findings of a RASopathy. Recognition of the common perinatal findings of these disorders should facilitate both their prenatal and neonatal diagnosis. © 2014 Wiley Periodicals, Inc.

Behavioral Characteristics and Neurobiological Substrates Shared by Pavlovian Sign-Tracking and Drug Abuse

PubMed Central

Tomie, Arthur; Grimes, Kathryn L.; Pohorecky, Larissa A.

2008-01-01

Drug abuse researchers have noted striking similarities between behaviors elicited by Pavlovian sign-tracking procedures and prominent symptoms of drug abuse. In Pavlovian sign-tracking procedures, repeated paired presentations of a small object (conditioned stimulus, CS) with a reward (unconditioned stimulus, US) elicits a conditioned response (CR) that typically consists of approaching the CS, contacting the CS, and expressing consummatory responses at the CS. Sign-tracking CR performance is poorly controlled and exhibits spontaneous recovery and long-term retention, effects that resemble relapse. Sign-tracking resembles psychomotor activation, a syndrome of behavioral responses evoked by addictive drugs, and the effects of sign-tracking on corticosterone levels and activation of dopamine pathways resemble the neurobiological effects of abused drugs. Finally, the neurobiological profile of individuals susceptible to sign-tracking resembles the pathophysiological profile of vulnerability to drug abuse, and vulnerability to sign-tracking predicts vulnerability to impulsive responding and alcohol self-administration. Implications of sign-tracking for models of drug addiction are considered. PMID:18234349

Structure and function of Enterotoxigenic Escherichia coli fimbriae from differing assembly pathways

PubMed Central

Mortezaei, Narges; Epler, Chelsea R.; Shao, Paul P.; Shirdel, Mariam; Singh, Bhupender; McVeigh, Annette; Uhlin, Bernt Eric; Savarino, Stephen J.; Andersson, Magnus; Bullitt, Esther

2014-01-01

Pathogenic enterotoxigenic Escherichia coli (ETEC) are the major bacterial cause of diarrhea in young children in developing countries and in travelers, causing significant mortality in children. Adhesive fimbriae are a prime virulence factor for ETEC, initiating colonization of the small intestinal epithelium. Similar to other Gram-negative bacteria, ETEC express one or more diverse fimbriae, some assembled by the chaperone-usher pathway and others by the alternate chaperone pathway. Here we elucidate structural and biophysical aspects and adaptations of each fimbrial type to its respective host niche. CS20 fimbriae are compared to CFA/I fimbriae, which are two ETEC fimbriae assembled via different pathways, and to P-fimbriae from uropathogenic E. coli. Many fimbriae unwind from their native helical filament to an extended linear conformation under force, thereby sustaining adhesion by reducing load at the point of contact between the bacterium and the target cell. CFA/I fimbriae require the least force to unwind, followed by CS20 fimbriae and then P-fimbriae, which require the highest unwinding force. We conclude from our electron microscopy reconstructions, modeling, and force spectroscopy data that the target niche plays a central role in the biophysical properties of fimbriae that are critical for bacterial pathophysiology. PMID:25355550

Delayed Early Primary Visual Pathway Development in Premature Infants: High Density Electrophysiological Evidence

PubMed Central

Tremblay, Emmanuel; Vannasing, Phetsamone; Roy, Marie-Sylvie; Lefebvre, Francine; Kombate, Damelan; Lassonde, Maryse; Lepore, Franco; McKerral, Michelle; Gallagher, Anne

2014-01-01

In the past decades, multiple studies have been interested in developmental patterns of the visual system in healthy infants. During the first year of life, differential maturational changes have been observed between the Magnocellular (P) and the Parvocellular (P) visual pathways. However, few studies investigated P and M system development in infants born prematurely. The aim of the present study was to characterize P and M system maturational differences between healthy preterm and fullterm infants through a critical period of visual maturation: the first year of life. Using a cross-sectional design, high-density electroencephalogram (EEG) was recorded in 31 healthy preterms and 41 fullterm infants of 3, 6, or 12 months (corrected age for premature babies). Three visual stimulations varying in contrast and spatial frequency were presented to stimulate preferentially the M pathway, the P pathway, or both systems simultaneously during EEG recordings. Results from early visual evoked potentials in response to the stimulation that activates simultaneously both systems revealed longer N1 latencies and smaller P1 amplitudes in preterm infants compared to fullterms. Moreover, preterms showed longer N1 and P1 latencies in response to stimuli assessing the M pathway at 3 months. No differences between preterms and fullterms were found when using the preferential P system stimulation. In order to identify the cerebral generator of each visual response, distributed source analyses were computed in 12-month-old infants using LORETA. Source analysis demonstrated an activation of the parietal dorsal region in fullterm infants, in response to the preferential M pathway, which was not seen in the preterms. Overall, these findings suggest that the Magnocellular pathway development is affected in premature infants. Although our VEP results suggest that premature children overcome, at least partially, the visual developmental delay with time, source analyses reveal abnormal brain activation of the Magnocellular pathway at 12 months of age. PMID:25268226

More than blindsight: Case report of a child with extraordinary visual capacity following perinatal bilateral occipital lobe injury.

PubMed

Mundinano, Inaki-Carril; Chen, Juan; de Souza, Mitchell; Sarossy, Marc G; Joanisse, Marc F; Goodale, Melvyn A; Bourne, James A

2017-11-13

Injury to the primary visual cortex (V1, striate cortex) and the geniculostriate pathway in adults results in cortical blindness, abolishing conscious visual perception. Early studies by Larry Weiskrantz and colleagues demonstrated that some patients with an occipital-lobe injury exhibited a degree of unconscious vision and visually-guided behaviour within the blind field. A more recent focus has been the observed phenomenon whereby early-life injury to V1 often results in the preservation of visual perception in both monkeys and humans. These findings initiated a concerted effort on multiple fronts, including nonhuman primate studies, to uncover the neural substrate/s of the spared conscious vision. In both adult and early-life cases of V1 injury, evidence suggests the involvement of the Middle Temporal area (MT) of the extrastriate visual cortex, which is an integral component area of the dorsal stream and is also associated with visually-guided behaviors. Because of the limited number of early-life V1 injury cases for humans, the outstanding question in the field is what secondary visual pathways are responsible for this extraordinary capacity? Here we report for the first time a case of a child (B.I.) who suffered a bilateral occipital-lobe injury in the first two weeks postnatally due to medium-chain acyl-Co-A dehydrogenase deficiency. At 6 years of age, B.I. underwent a battery of neurophysiological tests, as well as structural and diffusion MRI and ophthalmic examination at 7 years. Despite the extensive bilateral occipital cortical damage, B.I. has extensive conscious visual abilities, is not blind, and can use vision to navigate his environment. Furthermore, unlike blindsight patients, he can readily and consciously identify happy and neutral faces and colors, tasks associated with ventral stream processing. These findings suggest significant re-routing of visual information. To identify the putative visual pathway/s responsible for this ability, MRI tractography of secondary visual pathways connecting MT with the lateral geniculate nucleus (LGN) and the inferior pulvinar (PI) were analysed. Results revealed an increased PI-MT pathway in the left hemisphere, suggesting that this pulvinar relay could be the neural pathway affording the preserved visual capacity following an early-life lesion of V1. These findings corroborate anatomical evidence from monkeys showing an enhanced PI-MT pathway following an early-life lesion of V1, compared to adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

The role of human ventral visual cortex in motion perception

PubMed Central

Saygin, Ayse P.; Lorenzi, Lauren J.; Egan, Ryan; Rees, Geraint; Behrmann, Marlene

2013-01-01

Visual motion perception is fundamental to many aspects of visual perception. Visual motion perception has long been associated with the dorsal (parietal) pathway and the involvement of the ventral ‘form’ (temporal) visual pathway has not been considered critical for normal motion perception. Here, we evaluated this view by examining whether circumscribed damage to ventral visual cortex impaired motion perception. The perception of motion in basic, non-form tasks (motion coherence and motion detection) and complex structure-from-motion, for a wide range of motion speeds, all centrally displayed, was assessed in five patients with a circumscribed lesion to either the right or left ventral visual pathway. Patients with a right, but not with a left, ventral visual lesion displayed widespread impairments in central motion perception even for non-form motion, for both slow and for fast speeds, and this held true independent of the integrity of areas MT/V5, V3A or parietal regions. In contrast with the traditional view in which only the dorsal visual stream is critical for motion perception, these novel findings implicate a more distributed circuit in which the integrity of the right ventral visual pathway is also necessary even for the perception of non-form motion. PMID:23983030

CsWRKY46, a WRKY transcription factor from cucumber, confers cold resistance in transgenic-plant by regulating a set of cold-stress responsive genes in an ABA-dependent manner.

PubMed

Zhang, Ying; Yu, Hongjun; Yang, Xueyong; Li, Qiang; Ling, Jian; Wang, Hong; Gu, Xingfang; Huang, Sanwen; Jiang, Weijie

2016-11-01

Plant WRKY transcription factors are trans-regulatory proteins that are involved in plant immune responses, development and senescence; however, their roles in abiotic stress are still not well understood, especially in the horticultural crop cucumber. In this study, a novel cucumber WRKY gene, CsWRKY46 was cloned and identified, which was up-regulated in response to cold stress and exogenous abscisic acid (ABA) treatment. CsWRKY46 is belonging to group II of the WRKY family, CsWRKY46 was found exclusively in the nucleus, as indicated by a transient expression assay. Yeast one-hybrid assay shown that CsWRKY46 interact with the W-box in the promoter of ABI5. Transgenic Arabidopsis lines over-expressing CsWRKY46, WRK46-OE1 and WRK46-OE5 had higher seedling survival rates upon freezing treatment compared with that of the wild-type. The above over-expression lines also showed much a higher proline accumulation, less electrolyte leakage and lower malondialdehyde (MDA) levels. Furthermore, the CsWRKY46 overexpression lines were hypersensitive to ABA during seed germination, but the seedlings were not. Quantitative RT-PCR analyses revealed that the expression levels of the ABA-responsive transcription factor ABI5 were higher in the WRKY46-OE lines than in wild-type and that the overexpression of CsWRKY46 increased the expression of stress-inducible genes, including RD29A and COR47. Taken together, our results demonstrated that CsWRKY46 from cucumber conferred cold tolerance to transgenic plants and positively regulated the cold signaling pathway in an ABA-dependent manner. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Spatiotemporal expression of chondroitin sulfate sulfotransferases in the postnatal developing mouse cerebellum.

PubMed

Ishii, Maki; Maeda, Nobuaki

2008-08-01

Chondroitin sulfate (CS) proteoglycans are major components of the cell surface and the extracellular matrix in the developing brain and bind to various proteins via CS chains in a CS structure-dependent manner. This study demonstrated the expression pattern of three CS sulfotransferase genes, dermatan 4-O-sulfotransferase (D4ST), uronyl 2-O-sulfotransferase (UST), and N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST), in the mouse postnatal cerebellum. These sulfotransferases are responsible for the biosynthesis of oversulfated structures in CS chains such as B, D, and E units, which constitute the binding sites for various heparin-binding proteins. Real-time reverse transcription-polymerase chain reaction analysis indicated that the expression of UST increased remarkably during cerebellar development. The amounts of B and D units, which are generated by UST activity, in the cerebellar CS chains also increased during development. In contrast, the expression of GalNAc4S-6ST and its biosynthetic product, E unit, decreased during postnatal development. In situ hybridization experiments revealed the levels of UST and GalNAc4S-6ST mRNAs to correlate inversely in many cells including Purkinje cells, granule cells in the external granular layer, and inhibitory interneurons. In these neurons, the expression of UST increased and that of GalNAc4S-6ST decreased during development and/or maturation. D4ST was also expressed by many neurons, but its expression was not simply correlated with development, which might contribute to the diversification of CS structures expressed by distinct neurons. These results suggest that the CS structures of various cerebellar neurons change during development and such changes of CS are involved in the regulation of various signaling pathways.

A smart pH-responsive nano-carrier as a drug delivery system for the targeted delivery of ursolic acid: suppresses cancer growth and metastasis by modulating P53/MMP-9/PTEN/CD44 mediated multiple signaling pathways.

PubMed

Jiang, Kai; Chi, Ting; Li, Tao; Zheng, Guirong; Fan, Lulu; Liu, Yajun; Chen, Xiufen; Chen, Sijia; Jia, Lee; Shao, Jingwei

2017-07-13

Ursolic acid (UA) has been recently used as a promising anti-tumor and cancer metastatic chemo-preventive agent due to its low toxicity and liver-protecting property. However, the low bioavailability and nonspecific tumor targeting restrict its further clinical application. To address the problem, a silica-based mesoporous nanosphere (MSN) controlled-release drug delivery system (denoted UA@M-CS-FA) was designed and successfully synthesized, and was functionalized with folic acid (FA) and pH-sensitive chitosan (CS) for the targeted delivery of UA to folate receptor (FR) positive tumor cells. UA@M-CS-FA were spherical with mean diameter below 150 nm, and showed about -20 mV potential. Meanwhile, UA@M-CS-FA exhibited a pH-sensitive release manner and high cellular uptake in FR over-expressing HeLa cancer cells. Also, in vitro cellular assays suggested that UA@M-CS-FA inhibited cancer cell growth, invasion and migration. Mechanistically, UA@M-CS-FA induced cancer cell apoptosis and inhibited migration via cell cycle arrest in the G0/G1 stage, regulating the PARP/Bcl-2/MMP-9/CD44/PTEN/P53. Importantly, in vivo experiments further confirmed that UA@M-CS-FA significantly suppressed the tumor progression and lung metastasis in tumor-bearing nude mice. Immunohistochemical analysis revealed that UA@M-CS-FA treatment regulated CD44, a biomarker of cancer metastasis. Overall, our data demonstrated that a CS and FA modified MSN controlled-release drug delivery system could help broaden the usage of UA and reflect the great application potential of the UA as an anticancer or cancer metastatic chemopreventive agent.

A Mouse Model of Visual Perceptual Learning Reveals Alterations in Neuronal Coding and Dendritic Spine Density in the Visual Cortex.

PubMed

Wang, Yan; Wu, Wei; Zhang, Xian; Hu, Xu; Li, Yue; Lou, Shihao; Ma, Xiao; An, Xu; Liu, Hui; Peng, Jing; Ma, Danyi; Zhou, Yifeng; Yang, Yupeng

2016-01-01

Visual perceptual learning (VPL) can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF) for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS) and a 55% gain in visual acuity (VA). Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1) than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.

Usefulness of high-speed rotational coronary venous angiography during cardiac resynchronization therapy.

PubMed

Blendea, Dan; Mansour, Moussa; Shah, Ravi V; Chung, Jeffrey; Nandigam, Veena; Heist, E Kevin; Mela, Theofanie; Reddy, Vivek Y; Manzke, Robert; McPherson, Craig A; Ruskin, Jeremy N; Singh, Jagmeet P

2007-11-15

Standard coronary venous angiography (SCVA) provides a static, fixed projection of the coronary venous (CV) tree. High-speed rotational coronary venous angiography (RCVA) is a novel method of mapping CV anatomy using dynamic, multiangle visualization. The purpose of this study was to assess the value of RCVA during cardiac resynchronization therapy. Digitally acquired rotational CV angiograms from 49 patients (mean age 69 +/- 11 years) who underwent left ventricular lead implantation were analyzed. RCVA, which uses rapid isocentric rotation over a 110 degrees arc, acquiring 120 frames/angiogram, was compared with SCVA, defined as 2 static orthogonal views: right anterior oblique 45 degrees and left anterior oblique 45 degrees . RCVA demonstrated that the posterior vein-to-coronary sinus (CS) angle and the left marginal vein-to-CS angle were misclassified in 5 and 11 patients, respectively, using SCVA. RCVA identified a greater number of second-order tributaries with diameters >1.5 mm than SCVA. The CV branch selected for lead placement was initially identified in 100% of patients using RCVA but in only 74% of patients using SCVA. RCVA showed that the best angiographic view for visualizing the CS and its tributaries differed significantly among different areas of the CV tree and among patients. The area of the CV tree that showed less variability was the CS ostium, which had a fairly constant relation with the spine in shallow right anterior oblique and left anterior oblique projections. In conclusion, RCVA provided a more precise map of CV anatomy and the spatial relation of venous branches. It allowed the identification of fluoroscopic views that could facilitate cannulation of the CS. The final x-ray view displaying the appropriate CV branch for left ventricular lead implantation was often different from the conventional left anterior oblique and right anterior oblique views. RCVA identified the target branch for lead implantation more often than SCVA.

Electrophoretic separation of alginic sodium diester and sodium hexametaphosphate in chondroitin sulfate that interfere with the cetylpyridinium chloride titration assay.

PubMed

Weiguo, Zhang; Giancaspro, Gabriel; Adams, Kristie M; Neal-Kababick, James; Hildreth, Jana; Li, Aishan; Roman, Mark C; Betz, Joseph M

2014-01-01

The most commonly used chondroitin sulfate (CS) assay method is cetylpyridinium chloride (CPC) titration. Cellulose acetate membrane electrophoresis (CAME) is the technique used for detection of impurities in the U.S. Pharmacopeia's CS monograph. Because CPC titration is a relatively nonspecific quantitative technique, the apparent amount of CS as determined by CPC titration alone may not reflect the true amount of CS due to possible interference with the CPC assay by impurities that contain CPC titratable functional groups. When CAME is used in conjunction with CPC titration, certain non-CS and adulterants can be visualized and estimated, and a true value for CS can be assigned once the presence of these non-CS impurities has been ruled out. This study examines conjunct application of CPC and CAME in ascertaining CS assay and purity in the presence of certain adulterants. These include propylene glycol alginate sulfate sodium, known in commerce as alginic sodium diester (ASD), and Zero One (Z1), a water-soluble agent newly reported in the CS marketplace and subsequently identified as sodium hexametaphosphate. ASD, Z1, and CS are similar in physical appearance and solubility in water and ethanol. They are also titratable anions and form ionic pairs with CPC, therefore interfering with the CPC titration assay for CS CAME separates these adulterants from each other and from CS by differences in their electrophoretic mobility. CAME is able to detect these impurities in CS at levels as low as 0.66% by weight. Although it is recommended that a method for detecting impurities (e.g., CAME) be used in cormbination with relatively nonspecific assay methods such as CPC titration, this is seldom done in practice. Assay results for CS derived fromn CPC titration may, therefore, be misleading, leaving the CS supply chain vulnerable to adulteration. In this study, the authors investigated ASD and Z1 adulteration of CS and developed an electrophoretic separation of these adulterants in CS and procedures to isolate ASD from CS matrixes containing these adulterants. The authors describe in this paper utilization of an orthogonal approach to establish the identity of Z1 as sodium hexametaphosphate and to confirm the identity of ASD, including ethanol fractionation, FTIR spectroscopy, differential scanning calorimetry, and NMR spectroscopy. The authors suggest that CAME is a cost-effective and easy to use methodfor detecting certain impurities in CS raw ingredients and recommend that CPC and CAME be used in combination by QC laboratories as a means of effectively deterring the practice of adulterating CS raw materials with the known adulterants ASD and Z1 and/or other non-chondroitin substances that can be separated from CSby CAME and that exhibit CPC titration behavior similar to CS.

Complete genome sequence of the phenanthrene-degrading soil bacterium Delftia acidovorans Cs1-4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shetty, Ameesha R.; de Gannes, Vidya; Obi, Chioma C.

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants and microbial biodegradation is an important means of remediation of PAH-contaminated soil. Delftia acidovorans Cs1-4 (formerly Delftia sp. Cs1-4) was isolated by using phenanthrene as the sole carbon source from PAH contaminated soil in Wisconsin. Its full genome sequence was determined to gain insights into a mechanisms underlying biodegradation of PAH. Three genomic libraries were constructed and sequenced: an Illumina GAii shotgun library (916,416,493 reads), a 454 Titanium standard library (770,171 reads) and one paired-end 454 library (average insert size of 8 kb, 508,092 reads). The initial assembly contained 40 contigs inmore » two scaffolds. The 454 Titanium standard data and the 454 paired end data were assembled together and the consensus sequences were computationally shredded into 2 kb overlapping shreds. Illumina sequencing data was assembled, and the consensus sequence was computationally shredded into 1.5 kb overlapping shreds. Gaps between contigs were closed by editing in Consed, by PCR and by Bubble PCR primer walks. A total of 182 additional reactions were needed to close gaps and to raise the quality of the finished sequence. The final assembly is based on 253.3 Mb of 454 draft data (averaging 38.4 X coverage) and 590.2 Mb of Illumina draft data (averaging 89.4 X coverage). The genome of strain Cs1-4 consists of a single circular chromosome of 6,685,842 bp (66.7 %G+C) containing 6,028 predicted genes; 5,931 of these genes were protein-encoding and 4,425 gene products were assigned to a putative function. Genes encoding phenanthrene degradation were localized to a 232 kb genomic island (termed the phn island), which contained near its 3’ end a bacteriophage P4-like integrase, an enzyme often associated with chromosomal integration of mobile genetic elements. Other biodegradation pathways reconstructed from the genome sequence included: benzoate (by the acetyl-CoA pathway), styrene, nicotinic acid (by the maleamate pathway) and the pesticides Dicamba and Fenitrothion. Lastly, determination of the complete genome sequence of D. acidovorans Cs1-4 has provided new insights the microbial mechanisms of PAH biodegradation that may shape the process in the environment.« less

Complete genome sequence of the phenanthrene-degrading soil bacterium Delftia acidovorans Cs1-4

DOE PAGES

Shetty, Ameesha R.; de Gannes, Vidya; Obi, Chioma C.; ...

2015-08-15

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants and microbial biodegradation is an important means of remediation of PAH-contaminated soil. Delftia acidovorans Cs1-4 (formerly Delftia sp. Cs1-4) was isolated by using phenanthrene as the sole carbon source from PAH contaminated soil in Wisconsin. Its full genome sequence was determined to gain insights into a mechanisms underlying biodegradation of PAH. Three genomic libraries were constructed and sequenced: an Illumina GAii shotgun library (916,416,493 reads), a 454 Titanium standard library (770,171 reads) and one paired-end 454 library (average insert size of 8 kb, 508,092 reads). The initial assembly contained 40 contigs inmore » two scaffolds. The 454 Titanium standard data and the 454 paired end data were assembled together and the consensus sequences were computationally shredded into 2 kb overlapping shreds. Illumina sequencing data was assembled, and the consensus sequence was computationally shredded into 1.5 kb overlapping shreds. Gaps between contigs were closed by editing in Consed, by PCR and by Bubble PCR primer walks. A total of 182 additional reactions were needed to close gaps and to raise the quality of the finished sequence. The final assembly is based on 253.3 Mb of 454 draft data (averaging 38.4 X coverage) and 590.2 Mb of Illumina draft data (averaging 89.4 X coverage). The genome of strain Cs1-4 consists of a single circular chromosome of 6,685,842 bp (66.7 %G+C) containing 6,028 predicted genes; 5,931 of these genes were protein-encoding and 4,425 gene products were assigned to a putative function. Genes encoding phenanthrene degradation were localized to a 232 kb genomic island (termed the phn island), which contained near its 3’ end a bacteriophage P4-like integrase, an enzyme often associated with chromosomal integration of mobile genetic elements. Other biodegradation pathways reconstructed from the genome sequence included: benzoate (by the acetyl-CoA pathway), styrene, nicotinic acid (by the maleamate pathway) and the pesticides Dicamba and Fenitrothion. Lastly, determination of the complete genome sequence of D. acidovorans Cs1-4 has provided new insights the microbial mechanisms of PAH biodegradation that may shape the process in the environment.« less

Resilience to the contralateral visual field bias as a window into object representations

PubMed Central

Garcea, Frank E.; Kristensen, Stephanie; Almeida, Jorge; Mahon, Bradford Z.

2016-01-01

Viewing images of manipulable objects elicits differential blood oxygen level-dependent (BOLD) contrast across parietal and dorsal occipital areas of the human brain that support object-directed reaching, grasping, and complex object manipulation. However, it is unknown which object-selective regions of parietal cortex receive their principal inputs from the ventral object-processing pathway and which receive their inputs from the dorsal object-processing pathway. Parietal areas that receive their inputs from the ventral visual pathway, rather than from the dorsal stream, will have inputs that are already filtered through object categorization and identification processes. This predicts that parietal regions that receive inputs from the ventral visual pathway should exhibit object-selective responses that are resilient to contralateral visual field biases. To test this hypothesis, adult participants viewed images of tools and animals that were presented to the left or right visual fields during functional magnetic resonance imaging (fMRI). We found that the left inferior parietal lobule showed robust tool preferences independently of the visual field in which tool stimuli were presented. In contrast, a region in posterior parietal/dorsal occipital cortex in the right hemisphere exhibited an interaction between visual field and category: tool-preferences were strongest contralateral to the stimulus. These findings suggest that action knowledge accessed in the left inferior parietal lobule operates over inputs that are abstracted from the visual input and contingent on analysis by the ventral visual pathway, consistent with its putative role in supporting object manipulation knowledge. PMID:27160998

CsSCL1 is differentially regulated upon maturation in chestnut microshoots and is specifically expressed in rooting-competent cells.

PubMed

Vielba, Jesús M; Díaz-Sala, Carmen; Ferro, Enrique; Rico, Saleta; Lamprecht, María; Abarca, Dolores; Ballester, Antonio; Sánchez, Conchi

2011-10-01

The Castanea sativa SCL1 gene (CsSCL1) has previously been shown to be induced by auxin during adventitious root (AR) formation in rooting-competent microshoots. However, its expression has not previously been analyzed in rooting-incompetent shoots. This study focuses on the regulation of CsSCL1 during maturation and the role of the gene in the formation of AR. The expression of CsSCL1 in rooting-incompetent microshoots and other tissues was investigated by quantitative reverse transcriptase--polymerase chain reaction. The analysis was complemented by in situ hybridization of the basal segments of rooting-competent and --incompetent microshoots during AR induction, as well as in AR and lateral roots. It was found that CsSCL1 is upregulated by auxin in a cell-type- and phase-dependent manner during the induction of AR. In root-forming shoots, CsSCL1 mRNA was specifically located in the cambial zone and derivative cells, which are rooting-competent cells, whereas in rooting-incompetent shoots the hybridization signal was more diffuse and evenly distributed through the phloem and parenchyma. CsSCL1 expression was also detected in lateral roots and axillary buds. The different CsSCL1 expression patterns in rooting-competent and -incompetent microshoots, together with the specific location of transcripts in cell types involved in root meristem initiation and in the root primordia of AR and lateral roots, indicate an important role for the gene in determining whether certain cells will enter the root differentiation pathway and its involvement in meristem maintenance.

Not all glucocorticoid-induced obesity is the same: differences in adiposity among various diagnostic groups of Cushing syndrome.

PubMed

London, E; Lodish, M; Keil, M; Lyssikatos, C; de la Luz Sierra, M; Nesterova, M; Stratakis, C A

2014-11-01

The cAMP signaling pathway is implicated in bilateral adrenocortical hyperplasias (BAHs), which are often associated with ACTH-independent Cushing syndrome (CS). Although CS is invariably associated with obesity and is frequently associated with PKA signaling defects, we recently reported that its different forms appear to also present with variable weight gain and adiposity. The present study was aimed at characterizing further the phenotypic and molecular differences in periadrenal adipose tissue (PAT) among patients with subtypes of CS, by anthropometric/biochemical analyses and quantification of PKA expression and activity in BAHs in comparison to a non-CS group with aldosterone producing adenomas (APAs). Glucocorticoid levels, serum parameters, and BMI were analyzed among a larger patient cohort including those with different forms of CS, APAs, and Cushing disease. Abdominal CT scans were available for a small subset of patients examined for fat distribution. PAT collected during adrenalectomy was assayed for PKA activity, cAMP, and PKA expression. BMI and BMI z-score were lower in adults with PPNAD with PRKAR1A mutations and in pediatric patients with PPNAD with and without PRKAR1A mutations, respectively. Patients with PPNAD had higher cAMP levels in PAT and different fat distribution. Thus, PKA activity in PAT differed between CS diagnostic groups. Increased cAMP and PKA activity may have contributed to phenotypic differences among subtypes of CS. In agreement with the known roles of cAMP signaling in the regulation of adiposity, patients with PPNAD were less obese than other patients with CS. © Georg Thieme Verlag KG Stuttgart · New York.

Advanced enzymology, expression profile and immune response of Clonorchis sinensis hexokinase show its application potential for prevention and control of clonorchiasis.

PubMed

Chen, Tingjin; Yu, Jinyun; Tang, Zeli; Xie, Zhizhi; Lin, Zhipeng; Sun, Hengchang; Wan, Shuo; Li, Xuerong; Huang, Yan; Yu, Xinbing; Xu, Jin

2015-03-01

Approximately 35 million people are infected with Clonorchis sinensis (C. sinensis) globally, of whom 15 million are in China. Glycolytic enzymes are recognized as crucial molecules for trematode survival and have been targeted for vaccine and drug development. Hexokinase of C. sinensis (CsHK), as the first key regulatory enzyme of the glycolytic pathway, was investigated in the current study. There were differences in spatial structure and affinities for hexoses and phosphate donors between CsHK and HKs from humans or rats, the definitive hosts of C. sinensis. Effectors (AMP, PEP, and citrate) and a small molecular inhibitor regulated the enzymatic activity of rCsHK, and various allosteric systems were detected. CsHK was distributed in the worm extensively as well as in liver tissue and serum from C. sinensis infected rats. Furthermore, high-level specific IgG1 and IgG2a were induced in rats by immunization with rCsHK. The enzymatic activity of CsHK was suppressed by the antibody in vitro. Additionally, the survival of C. sinensis was inhibited by the antibody in vivo and in vitro. Due to differences in putative spatial structure and enzymology between CsHK and HK from the host, its extensive distribution in adult worms, and its expression profile as a component of excretory/secretory products, together with its good immunogenicity and immunoreactivity, as a key glycolytic enzyme, CsHK shows potential as a vaccine and as a promising drug target for Clonorchiasis.

Advanced Enzymology, Expression Profile and Immune Response of Clonorchis sinensis Hexokinase Show Its Application Potential for Prevention and Control of Clonorchiasis

PubMed Central

Tang, Zeli; Xie, Zhizhi; Lin, Zhipeng; Sun, Hengchang; Wan, Shuo; Li, Xuerong; Huang, Yan; Yu, Xinbing; Xu, Jin

2015-01-01

Background Approximately 35 million people are infected with Clonorchis sinensis (C. sinensis) globally, of whom 15 million are in China. Glycolytic enzymes are recognized as crucial molecules for trematode survival and have been targeted for vaccine and drug development. Hexokinase of C. sinensis (CsHK), as the first key regulatory enzyme of the glycolytic pathway, was investigated in the current study. Principal Findings There were differences in spatial structure and affinities for hexoses and phosphate donors between CsHK and HKs from humans or rats, the definitive hosts of C. sinensis. Effectors (AMP, PEP, and citrate) and a small molecular inhibitor regulated the enzymatic activity of rCsHK, and various allosteric systems were detected. CsHK was distributed in the worm extensively as well as in liver tissue and serum from C. sinensis infected rats. Furthermore, high-level specific IgG1 and IgG2a were induced in rats by immunization with rCsHK. The enzymatic activity of CsHK was suppressed by the antibody in vitro. Additionally, the survival of C. sinensis was inhibited by the antibody in vivo and in vitro. Conclusions/Significance Due to differences in putative spatial structure and enzymology between CsHK and HK from the host, its extensive distribution in adult worms, and its expression profile as a component of excretory/secretory products, together with its good immunogenicity and immunoreactivity, as a key glycolytic enzyme, CsHK shows potential as a vaccine and as a promising drug target for Clonorchiasis. PMID:25799453

Emotional eating and Pavlovian learning: does negative mood facilitate appetitive conditioning?

PubMed

Bongers, Peggy; van den Akker, Karolien; Havermans, Remco; Jansen, Anita

2015-06-01

Emotional eating has been suggested to be a learned behaviour; more specifically, classical conditioning processes might be involved in its development. In the present study we investigated whether a negative mood facilitates appetitive conditioning and whether trait impulsivity influences this process. After undergoing either a negative or neutral mood induction, participants were subjected to a differential classical conditioning procedure, using neutral stimuli and appetizing food. Two initially neutral distinctive vases with flowers were (CS+) or were not (CS-) paired with chocolate mousse intake. We measured participants' expectancy and desire to eat (4 CS+ and 4 CS- trials), salivation response, and actual food intake. The BIS-11 was administered to assess trait impulsivity. In both mood conditions, participants showed a classically conditioned appetite. Unexpectedly, there was no evidence of facilitated appetitive learning in a negative mood with regard to expectancy, desire, salivation, or intake. However, immediately before the taste test, participants in the negative mood condition reported a stronger desire to eat in the CS+ compared to the CS- condition, while no such effect occurred in the neutral group. An effect of impulsivity was found with regard to food intake in the neutral mood condition: high-impulsive participants consumed less food when presented with the CS+ compared to the CS-, and also less than low-impulsive participants. An alternative pathway to appetitive conditioning with regard to emotions is that it is not the neutral stimuli, but the emotions themselves that become conditioned stimuli and elicit appetitive responses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unexpected source of Fukushima-derived radiocesium to the coastal ocean of Japan

PubMed Central

Sanial, Virginie; Buesseler, Ken O.; Charette, Matthew A.; Nagao, Seiya

2017-01-01

There are 440 operational nuclear reactors in the world, with approximately one-half situated along the coastline. This includes the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), which experienced multiple reactor meltdowns in March 2011 followed by the release of radioactivity to the marine environment. While surface inputs to the ocean via atmospheric deposition and rivers are usually well monitored after a nuclear accident, no study has focused on subterranean pathways. During our study period, we found the highest cesium-137 (137Cs) levels (up to 23,000 Bq⋅m−3) outside of the FDNPP site not in the ocean, rivers, or potable groundwater, but in groundwater beneath sand beaches over tens of kilometers away from the FDNPP. Here, we present evidence of a previously unknown, ongoing source of Fukushima-derived 137Cs to the coastal ocean. We postulate that these beach sands were contaminated in 2011 through wave- and tide-driven exchange and sorption of highly radioactive Cs from seawater. Subsequent desorption of 137Cs and fluid exchange from the beach sands was quantified using naturally occurring radium isotopes. This estimated ocean 137Cs source (0.6 TBq⋅y−1) is of similar magnitude as the ongoing releases of 137Cs from the FDNPP site for 2013–2016, as well as the input of Fukushima-derived dissolved 137Cs via rivers. Although this ongoing source is not at present a public health issue for Japan, the release of Cs of this type and scale needs to be considered in nuclear power plant monitoring and scenarios involving future accidents. PMID:28973919

Enhanced paracellular and transcellular paclitaxel permeation by chitosan-vitamin E succinate- N-acetyl- l-cysteine copolymer on Caco-2 cell monolayer

NASA Astrophysics Data System (ADS)

Lian, He; Zhang, Tianhong; Sun, Jin; Pu, Xiaohui; Tang, Yilin; Zhang, Youxi; He, Zhonggui

2014-04-01

The aim of this study was to evaluate the underlying mechanism of enhanced oral absorption of paclitaxel (PTX)-loaded chitosan-vitamin E succinate- N-acetyl- l-cysteine (CS-VES-NAC) nanomicelles from the cellular level. In aqueous solution, CS-VES-NAC copolymer self-assembled into the polymeric nanomicelles, with the size ranging from 190 to 240 nm and the drug loading content as high as 20.5 %. Cytotoxicity results showed that the PTX-loaded nanomicelles exhibited the similar effect to PTX solution (PTX-Sol) on Caco-2 cells, but no toxicity observed for blank CS-VES-NAC nanomicelles. The cellular uptake of PTX was significantly increased by CS-VES-NAC nanomicelles, compared with that of PTX-Sol, due to the possible escapement of P-glycoprotein (P-gp) efflux pumps by endocytosis pathway. Confocal laser scanning microscope (CLSM) images also confirmed CS-VES-NAC nanomicelles could be effectively internalized by Caco-2 cells. More importantly, P app value of PTX-loaded CS-VES-NAC nanomicelles was 2.3-fold higher than that of PTX-Sol, and the efflux ratio decreased by more than 10.8-fold for the nanomicelles. As a consequence of opening of tight junctions and P-gp inhibition induced by free CS-VES-NAC copolymer, the P app value of PTX was almost increased up to 19.5-fold. All the results indicate that CS-VES-NAC copolymer hold great promises as nanocarrier for antitumor drug oral delivery by improving paracellular and transcellular permeation.

Emergence of Orientation Selectivity in the Mammalian Visual Pathway

PubMed Central

Scholl, Benjamin; Tan, Andrew Y. Y.; Corey, Joseph

2013-01-01

Orientation selectivity is a property of mammalian primary visual cortex (V1) neurons, yet its emergence along the visual pathway varies across species. In carnivores and primates, elongated receptive fields first appear in V1, whereas in lagomorphs such receptive fields emerge earlier, in the retina. Here we examine the mouse visual pathway and reveal the existence of orientation selectivity in lateral geniculate nucleus (LGN) relay cells. Cortical inactivation does not reduce this orientation selectivity, indicating that cortical feedback is not its source. Orientation selectivity is similar for LGN relay cells spiking and subthreshold input to V1 neurons, suggesting that cortical orientation selectivity is inherited from the LGN in mouse. In contrast, orientation selectivity of cat LGN relay cells is small relative to subthreshold inputs onto V1 simple cells. Together, these differences show that although orientation selectivity exists in visual neurons of both rodents and carnivores, its emergence along the visual pathway, and thus its underlying neuronal circuitry, is fundamentally different. PMID:23804085

SPV: a JavaScript Signaling Pathway Visualizer.

PubMed

Calderone, Alberto; Cesareni, Gianni

2018-03-24

The visualization of molecular interactions annotated in web resources is useful to offer to users such information in a clear intuitive layout. These interactions are frequently represented as binary interactions that are laid out in free space where, different entities, cellular compartments and interaction types are hardly distinguishable. SPV (Signaling Pathway Visualizer) is a free open source JavaScript library which offers a series of pre-defined elements, compartments and interaction types meant to facilitate the representation of signaling pathways consisting of causal interactions without neglecting simple protein-protein interaction networks. freely available under Apache version 2 license; Source code: https://github.com/Sinnefa/SPV_Signaling_Pathway_Visualizer_v1.0. Language: JavaScript; Web technology: Scalable Vector Graphics; Libraries: D3.js. sinnefa@gmail.com.

Visual Outcomes in Pediatric Optic Pathway Glioma After Conformal Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Awdeh, Richard M.; Kiehna, Erin N.; Drewry, Richard D.

Purpose: To assess visual outcome prospectively after conformal radiation therapy (CRT) in children with optic pathway glioma. Methods and Materials: We used CRT to treat optic pathway glioma in 20 children (median age 9.3 years) between July 1997 and January 2002. We assessed changes in visual acuity using the logarithm of the minimal angle of resolution after CRT (54 Gy) with a median follow-up of 24 months. We included in the study children who underwent chemotherapy (8 patients) or resection (9 patients) before CRT. Results: Surgery played a major role in determining baseline (pre-CRT) visual acuity (better eye: P=.0431; worsemore » eye: P=.0032). The visual acuity in the worse eye was diminished at baseline (borderline significant) with administration of chemotherapy before CRT (P=.0726) and progression of disease prior to receiving CRT (P=.0220). In the worse eye, improvement in visual acuity was observed in patients who did not receive chemotherapy before CRT (P=.0289). Conclusions: Children with optic pathway glioma initially treated with chemotherapy prior to receiving radiation therapy have decreased visual acuity compared with those who receive primary radiation therapy. Limited surgery before radiation therapy may have a role in preserving visual acuity.« less

Structural basis and functions of abscisic acid receptors PYLs

PubMed Central

Zhang, Xing L.; Jiang, Lun; Xin, Qi; Liu, Yang; Tan, Jian X.; Chen, Zhong Z.

2015-01-01

Abscisic acid (ABA) plays a key role in many developmental processes and responses to adaptive stresses in plants. Recently, a new family of nucleocytoplasmic PYR/PYL/RCAR (PYLs) has been identified as bona fide ABA receptors. PYLs together with protein phosphatases type-2C (PP2Cs), Snf1 (Sucrose-non-fermentation 1)-related kinases subfamily 2 (SnRK2s) and downstream substrates constitute the core ABA signaling network. Generally, PP2Cs inactivate SnRK2s kinases by physical interaction and direct dephosphorylation. Upon ABA binding, PYLs change their conformations and then contact and inhibit PP2Cs, thus activating SnRK2s. Here, we reviewed the recent progress in research regarding the structures of the core signaling pathways of ABA, including the (+)-ABA, (−)-ABA and ABA analogs pyrabactin as well as 6AS perception by PYLs, SnRK2s mimicking PYLs in binding PP2Cs. PYLs inhibited PP2Cs in both the presence and absence of ABA and activated SnRK2s. The present review elucidates multiple ABA signal perception and transduction by PYLs, which might shed light on how to design small chemical compounds for improving plant performance in the future. PMID:25745428

A taxonomy of visualization tasks for the analysis of biological pathway data.

PubMed

Murray, Paul; McGee, Fintan; Forbes, Angus G

2017-02-15

Understanding complicated networks of interactions and chemical components is essential to solving contemporary problems in modern biology, especially in domains such as cancer and systems research. In these domains, biological pathway data is used to represent chains of interactions that occur within a given biological process. Visual representations can help researchers understand, interact with, and reason about these complex pathways in a number of ways. At the same time, these datasets offer unique challenges for visualization, due to their complexity and heterogeneity. Here, we present taxonomy of tasks that are regularly performed by researchers who work with biological pathway data. The generation of these tasks was done in conjunction with interviews with several domain experts in biology. These tasks require further classification than is provided by existing taxonomies. We also examine existing visualization techniques that support each task, and we discuss gaps in the existing visualization space revealed by our taxonomy. Our taxonomy is designed to support the development and design of future biological pathway visualization applications. We conclude by suggesting future research directions based on our taxonomy and motivated by the comments received by our domain experts.

Estimations of direct release rate of 137Cs and 90Sr to the ocean from the Fukushima Dai-ichi Nuclear Power Plant for five-and-a-half years

NASA Astrophysics Data System (ADS)

Tsumune, Daisuke; Aoyama, Michio; Tsubono, Takaki; Misumi, Kazuhiro; Tateda, Yutaka

2017-04-01

A series of accidents at the Fukushima Dai-ichi Nuclear Power Plant (1F NPP) following the earthquake and tsunami of 11 March 2011 resulted in the release of radioactive materials to the ocean by two major pathways, direct release from the accident site and atmospheric deposition. Additional release pathways by river input and runoff from 1F NPP site with precipitation and were also effective for coastal zone in the specific periods before starting direct release on March 26 2011. Direct release from 1F NPP site is dominant one year after the accident. We estimated the direct release rate of 137Cs and 90Sr for more than five-and-a-half years after the accident by the Regional Ocean Model System (ROMS). Direct release rate of 137Cs were estimated for five-and-a-half years after the accident by comparing simulated results and measured activities adjacent to the 1F NPP site(at 5,6 discharge and south discharge). Directly release rate of 137Cs was estimated to be the order of magnitude of 1014 Bq/day and decreased exponentially with time to be the order of magnitude of 109 Bq/day by the end of September 2016. Estimated direct release rate have exponentially reduced with constant rate since November 2011. Apparent half-life of direct release rate was estimated to be 346 days. The estimated total amounts of directly released 137Cs was 3.7±0.7 PBq for five and a half years. Simulated 137Cs activities attributable to direct release were in good agreement with observed activities, a result that implies the estimated direct release rate was reasonable. Simulated 137Cs activity affected off coast in the Fukushima prefecture. We used the measured 137Cs activities by the Tokyo Electric Power Company (TEPCO) for the estimation of direct release. The sea water samples were corrected from the coast. The averaged 137Cs activities from November 2013 to June 2016 were 391 and 383 Bq/m3 at 5,6 discharge and south discharge, respectively. The averaged 137Cs activities measured by the Nuclear Regulation Agency (NRA) is about five times smaller than the one by the TEPCO because the NRA corrected seawater samples at 300-500m offshore by ship. Horizontal resolution of the model was 1km x 1km, therefore it is important to consider the difference of activities in the sub-grid scale for the detailed estimations of direct release. 90Sr/137Cs activity ratio measured adjacent to the 1F NPP is variable with time. The 90Sr/137Cs activity ratio was 0.62 due to the global fallout before the accident. The 90Sr/137Cs activity ratio decreased to 0.01 after the accident before April 2011. And the ratio increased to 1 by September 2013. And then the ratio decreased to 0.1-1. After October 2015, the ratio decreased to 0.1-0.2. Directly release rate of 90Sr was estimated to be the order of magnitude of 1012 Bq/day and decreased to the order of magnitude of 108 Bq/day by the end of September 2016. The estimated total amounts of directly released 90Sr was 35 ± 7 TBq.

BCR/ABL downregulates DNA-PK(CS)-dependent and upregulates backup non-homologous end joining in leukemic cells.

PubMed

Poplawski, Tomasz; Blasiak, Janusz

2010-06-01

Non-homologous end joining (NHEJ) and homologous recombination repair (HRR) are the main mechanisms involved in the processing of DNA double strand breaks (DSBs) in humans. We showed previously that the oncogenic tyrosine kinase BCR/ABL stimulated DSBs repair by HRR. To evaluate the role of BCR/ABL in DSBs repair by NHEJ we examined the ability of leukemic BCR/ABL-expressing cell line BV173 to repair DNA damage induced by two DNA topoisomerase II inhibitors: etoposide and sobuzoxane. DNA lesions induced by sobuzoxane are repaired by a NHEJ pathway which is dependent on the catalytic subunit of protein kinase dependent on DNA (DNA-PK(CS); D-NHEJ), whereas damage evoked by etoposide are repaired by two distinct NHEJ pathways, dependent on or independent of DNA-PK(CS) (backup NHEJ, B-NHEJ). Cells incubated with STI571, a highly specific inhibitor of BCR/ABL, displayed resistance to these agents associated with an accelerated kinetics of DSBs repair, as measured by the neutral comet assay and pulsed field gel electrophoresis. However, in a functional NHEJ assay, cells preincubated with STI571 repaired DSBs induced by a restriction enzyme with a lower efficacy than without the preincubation and addition of wortmannin, a specific inhibitor of DNA-PK(CS), did not change efficacy of the NHEJ reaction. We suggest that BCR/ABL switch on B-NHEJ which is more error-prone then D-NHEJ and in such manner contribute to the increase of the genomic instability of leukemic cells.

The iRoCS Toolbox--3D analysis of the plant root apical meristem at cellular resolution.

PubMed

Schmidt, Thorsten; Pasternak, Taras; Liu, Kun; Blein, Thomas; Aubry-Hivet, Dorothée; Dovzhenko, Alexander; Duerr, Jasmin; Teale, William; Ditengou, Franck A; Burkhardt, Hans; Ronneberger, Olaf; Palme, Klaus

2014-03-01

To achieve a detailed understanding of processes in biological systems, cellular features must be quantified in the three-dimensional (3D) context of cells and organs. We described use of the intrinsic root coordinate system (iRoCS) as a reference model for the root apical meristem of plants. iRoCS enables direct and quantitative comparison between the root tips of plant populations at single-cell resolution. The iRoCS Toolbox automatically fits standardized coordinates to raw 3D image data. It detects nuclei or segments cells, automatically fits the coordinate system, and groups the nuclei/cells into the root's tissue layers. The division status of each nucleus may also be determined. The only manual step required is to mark the quiescent centre. All intermediate outputs may be refined if necessary. The ability to learn the visual appearance of nuclei by example allows the iRoCS Toolbox to be easily adapted to various phenotypes. The iRoCS Toolbox is provided as an open-source software package, licensed under the GNU General Public License, to make it accessible to a broad community. To demonstrate the power of the technique, we measured subtle changes in cell division patterns caused by modified auxin flux within the Arabidopsis thaliana root apical meristem. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

MEGADOCK-Web: an integrated database of high-throughput structure-based protein-protein interaction predictions.

PubMed

Hayashi, Takanori; Matsuzaki, Yuri; Yanagisawa, Keisuke; Ohue, Masahito; Akiyama, Yutaka

2018-05-08

Protein-protein interactions (PPIs) play several roles in living cells, and computational PPI prediction is a major focus of many researchers. The three-dimensional (3D) structure and binding surface are important for the design of PPI inhibitors. Therefore, rigid body protein-protein docking calculations for two protein structures are expected to allow elucidation of PPIs different from known complexes in terms of 3D structures because known PPI information is not explicitly required. We have developed rapid PPI prediction software based on protein-protein docking, called MEGADOCK. In order to fully utilize the benefits of computational PPI predictions, it is necessary to construct a comprehensive database to gather prediction results and their predicted 3D complex structures and to make them easily accessible. Although several databases exist that provide predicted PPIs, the previous databases do not contain a sufficient number of entries for the purpose of discovering novel PPIs. In this study, we constructed an integrated database of MEGADOCK PPI predictions, named MEGADOCK-Web. MEGADOCK-Web provides more than 10 times the number of PPI predictions than previous databases and enables users to conduct PPI predictions that cannot be found in conventional PPI prediction databases. In MEGADOCK-Web, there are 7528 protein chains and 28,331,628 predicted PPIs from all possible combinations of those proteins. Each protein structure is annotated with PDB ID, chain ID, UniProt AC, related KEGG pathway IDs, and known PPI pairs. Additionally, MEGADOCK-Web provides four powerful functions: 1) searching precalculated PPI predictions, 2) providing annotations for each predicted protein pair with an experimentally known PPI, 3) visualizing candidates that may interact with the query protein on biochemical pathways, and 4) visualizing predicted complex structures through a 3D molecular viewer. MEGADOCK-Web provides a huge amount of comprehensive PPI predictions based on docking calculations with biochemical pathways and enables users to easily and quickly assess PPI feasibilities by archiving PPI predictions. MEGADOCK-Web also promotes the discovery of new PPIs and protein functions and is freely available for use at http://www.bi.cs.titech.ac.jp/megadock-web/ .

Reconstruction of 137Cs activity in the ocean following the Fukushima Daiichi Nuclear Power Plant Accident

NASA Astrophysics Data System (ADS)

Tsumune, Daisuke; Aoyama, Michio; Tsubono, Takaki; Tateda, Yutaka; Misumi, Kazuhiro; Hayami, Hiroshi; Toyoda, Yasuhiro; Maeda, Yoshiaki; Yoshida, Yoshikatsu; Uematsu, Mitsuo

2014-05-01

A series of accidents at the Fukushima Dai-ichi Nuclear Power Plant following the earthquake and tsunami of 11 March 2011 resulted in the release of radioactive materials to the ocean by two major pathways, direct release from the accident site and atmospheric deposition. We reconstructed spatiotemporal variability of 137Cs activity in the ocean by the comparison model simulations and observed data. We employed a regional scale and the North Pacific scale oceanic dispersion models, an atmospheric transport model, a sediment transport model, a dynamic biological compartment model for marine biota and river runoff model to investigate the oceanic contamination. Direct releases of 137Cs were estimated for more than 2 years after the accident by comparing simulated results and observed activities very close to the site. The estimated total amounts of directly released 137Cs was 3.6±0.7 PBq. Directly release rate of 137Cs decreased exponentially with time by the end of December 2012 and then, was almost constant. The daily release rate of 137Cs was estimated to be 3.0 x 1010 Bq day-1 by the end of September 2013. The activity of directly released 137Cs was detectable only in the coastal zone after December 2012. Simulated 137Cs activities attributable to direct release were in good agreement with observed activities, a result that implies the estimated direct release rate was reasonable, while simulated 137Cs activities attributable to atmospheric deposition were low compared to measured activities. The rate of atmospheric deposition onto the ocean was underestimated because of a lack of measurements of dose rate and air activity of 137Cs over the ocean when atmospheric deposition rates were being estimated. Observed 137Cs activities attributable to atmospheric deposition in the ocean helped to improve the accuracy of simulated atmospheric deposition rates. Although there is no observed data of 137Cs activity in the ocean from 11 to 21 March 2011, observed data of marine biota should reflect the history of 137Cs activity in this early period. The comparisons between simulated 137Cs activity of marine biota by a dynamic biological compartment and observed data also suggest that simulated 137Cs activity attributable to atmospheric deposition was underestimated in this early period. In addition, river runoff model simulations suggest that the river flux of 137Cs to the ocean was effective to the 137Cs activity in the ocean in this early period. The sediment transport model simulations suggests that the inventory of 137Cs in sediment was less than 10

A randomized, open-label, multicenter study of the efficacy and safety of intravesical hyaluronic acid and chondroitin sulfate versus dimethyl sulfoxide in women with bladder pain syndrome/interstitial cystitis.

PubMed

Cervigni, Mauro; Sommariva, Monica; Tenaglia, Raffaele; Porru, Daniele; Ostardo, Edoardo; Giammò, Alessandro; Trevisan, Silvia; Frangione, Valeria; Ciani, Oriana; Tarricone, Rosanna; Pappagallo, Giovanni L

2017-04-01

Intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS) in women with bladder pain syndrome/interstitial cystitis (BPS/IC) has shown promising results. This study compared the efficacy, safety, and costs of intravesical HA/CS (Ialuril ® , IBSA) to dimethyl sulfoxide (DMSO). Randomized, open-label, multicenter study involving 110 women with BPS/IC. The allocation ratio (HA/CS:DMSO) was 2:1. Thirteen weekly instillations of HA (1.6%)/CS (2.0%) or 50% DMSO were given. Patients were evaluated at 3 (end-of-treatment) and 6 months. Primary endpoint was reduction in pain intensity at 6 months by visual analogue scale (VAS) versus baseline. Secondary efficacy measurements were quality of life and economic analyses. A significant reduction in pain intensity was observed at 6 months in both treatment groups versus baseline (P < 0.0001) in the intention-to-treat population. Treatment with HA/CS resulted in a greater reduction in pain intensity at 6 months compared with DMSO for the per-protocol population (mean VAS reduction 44.77 ± 25.07 vs. 28.89 ± 31.14, respectively; P = 0.0186). There were no significant differences between treatment groups in secondary outcomes. At least one adverse event was reported in 14.86% and 30.56% of patients in the HA/CS and DMSO groups, respectively. There were significantly fewer treatment-related adverse events for HA/CS versus DMSO (1.35% vs. 22.22%; P = 0.001). Considering direct healthcare costs, the incremental cost-effectiveness ratio of HA/CS versus DMSO fell between 3735€/quality-adjusted life years (QALY) and 8003€/QALY. Treatment with HA/CS appears to be as effective as DMSO with a potentially more favorable safety profile. Both treatments increased health-related quality of life, while HA/CS showed a more acceptable cost-effectiveness profile. © 2016 Wiley Periodicals, Inc.

Spot-Scanning Proton Radiation Therapy for Pediatric Chordoma and Chondrosarcoma: Clinical Outcome of 26 Patients Treated at Paul Scherrer Institute

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rombi, Barbara; ATreP; Ares, Carmen, E-mail: carmen.ares@psi.ch

Purpose: To evaluate the clinical results of fractionated spot-scanning proton radiation therapy (PT) in 26 pediatric patients treated at Paul Scherrer Institute for chordoma (CH) or chondrosarcoma (CS) of the skull base or axial skeleton. Methods and Materials: Between June 2000 and June 2010, 19 CH and 7 CS patients with tumors originating from the skull base (17) and the axial skeleton (9) were treated with PT. Mean age at the time of PT was 13.2 years. The mean prescribed dose was 74 Gy (relative biological effectiveness [RBE]) for CH and 66 Gy (RBE) for CS, at a dose ofmore » 1.8-2.0 Gy (RBE) per fraction. Results: Mean follow-up was 46 months. Actuarial 5-year local control (LC) rates were 81% for CH and 80% for CS. Actuarial 5-year overall survival (OS) was 89% for CH and 75% for CS. Two CH patients had local failures: one is alive with evidence of disease, while the other patient succumbed to local recurrence in the surgical pathway. One CS patient died of local progression of the disease. No high-grade late toxicities were observed. Conclusions: Spot-scanning PT for pediatric CH and CS patients resulted in excellent clinical outcomes with acceptable rates of late toxicity. Longer follow-up time and larger cohort are needed to fully assess tumor control and late effects of treatment.« less

Chitosan-based multifunctional nanomedicines and theranostics for targeted therapy of cancer.

PubMed

Fathi, Marziyeh; Majidi, Sima; Zangabad, Parham Sahandi; Barar, Jaleh; Erfan-Niya, Hamid; Omidi, Yadollah

2018-05-30

Nanotechnology as an emerging field has established inevitable impacts on nano-biomedicine and treatment of formidable diseases, inflammations, and malignancies. In this regard, substantial advances in the design of systems for delivery of therapeutic agents have emerged magnificent and innovative pathways in biomedical applications. Chitosan (CS) is derived via deacetylation of chitin as the second most abundant polysaccharide. Owing to the unique properties of CS (e.g., biocompatibility, biodegradability, bioactivity, mucoadhesion, cationic nature and functional groups), it is an excellent candidate for diverse biomedical and pharmaceutical applications such as drug/gene delivery, transplantation of encapsulated cells, tissue engineering, wound healing, antimicrobial purposes, etc. In this review, we will document, discuss, and provide some key insights toward design and application of miscellaneous nanoplatforms based on CS. The CS-based nanosystems (NSs) can be employed as advanced drug delivery systems (DDSs) in large part due to their remarkable physicochemical and biological characteristics. The abundant functional groups of CS allow the facile functionalization in order to engineer multifunctional NSs, which can simultaneously incorporate therapeutic agents, molecular targeting, and diagnostic/imaging capabilities in particular against malignancies. These multimodal NSs can be literally translated into clinical applications such as targeted diagnosis and therapy of cancer because they offer minimal systemic toxicity and maximal cytotoxicity against cancer cells and tumors. The recent developments in the CS-based NSs functionalized with targeting and imaging agents prove CS as a versatile polymer in targeted imaging and therapy. © 2018 Wiley Periodicals, Inc.

PATIKAweb: a Web interface for analyzing biological pathways through advanced querying and visualization.

PubMed

Dogrusoz, U; Erson, E Z; Giral, E; Demir, E; Babur, O; Cetintas, A; Colak, R

2006-02-01

Patikaweb provides a Web interface for retrieving and analyzing biological pathways in the Patika database, which contains data integrated from various prominent public pathway databases. It features a user-friendly interface, dynamic visualization and automated layout, advanced graph-theoretic queries for extracting biologically important phenomena, local persistence capability and exporting facilities to various pathway exchange formats.

Proline biosynthesis genes and their regulation under salinity stress in the euryhaline copepod Tigriopus californicus.

PubMed

Willett, Christopher S; Burton, Ronald S

2002-08-01

Diverse organisms regulate concentrations of intracellular organic osmolytes in response to changes in environmental salinity or desiccation. In marine crustaceans, accumulation of high concentrations of proline is a dominant component of response to hyperosmotic stress. In the euryhaline copepod Tigriopus californicus, synthesis of proline from its metabolic precursor glutamate is tightly regulated by changes in environmental salinity. Here, for the first time in a marine invertebrate, the genes responsible for this pathway have been cloned and characterized. The two proteins display the sequence features of homologous enzymes identified from other eukaryotes. One of the cloned genes, delta1-pyrroline-5-carboxylase reductase (P5CR), is demonstrated to have the reductase enzyme activity when expressed in proline-auxotroph bacteria, while the second, delta1-pyrroline-5-carboxylase synthase (P5CS), does not rescue proline-auxotroph bacteria. In contrast to results from higher plants, neither levels of P5CS nor P5CR mRNAs increase in response to salinity stress in T. californicus. Hence, regulation of proline synthesis during osmotic stress in T. californicus is likely mediated by some form of post-transcriptional regulation of either P5CS or P5CR. Understanding the regulation this pathway may elucidate the mechanisms limiting the salinity ranges of marine taxa. Copyright 2002 Elsevier Science Inc.

Immunosuppressants: tools to investigate the physiological role of cytokines.

PubMed

Quesniaux, V F

1993-11-01

The cyclic peptide Cyclosporine A (CsA) is best known as the immunosuppressive drug which has revolutionized organ transplantation. It selectively suppresses T cell activation by blocking the transcription of cytokine genes such as IL-2 at the level of transcription factor modulation. The structurally unrelated immunosuppressant FK 506 acts on the same pathway and blocks cytokine gene expression. In contrast, rapamycin, a structural analogue of FK 506, interferes with the immune response at a different level, by blocking the response induced by cytokines such as IL-2. Although these drugs have been most studied for their immunosuppressive activities, it is clear that their effects on cytokine pathways extend far beyond the sole IL-2-mediated responses involved in the immune response. For instance, CsA and FK 506 inhibit the transcription of IL-3, IL-4, IFN gamma, TNF alpha or GM-CSF by activated T cells, and rapamycin has been shown to block the response to various growth factors such as IL-3, IL-4 or IL-6. Here, we recap what is known about the effects of CsA, FK 506 and rapamycin on hematopoiesis in vitro and in vivo and extrapolate on what these drugs can teach us about the physiological role of cytokines for hematopoiesis.

Visual agnosia and focal brain injury.

PubMed

Martinaud, O

Visual agnosia encompasses all disorders of visual recognition within a selective visual modality not due to an impairment of elementary visual processing or other cognitive deficit. Based on a sequential dichotomy between the perceptual and memory systems, two different categories of visual object agnosia are usually considered: 'apperceptive agnosia' and 'associative agnosia'. Impaired visual recognition within a single category of stimuli is also reported in: (i) visual object agnosia of the ventral pathway, such as prosopagnosia (for faces), pure alexia (for words), or topographagnosia (for landmarks); (ii) visual spatial agnosia of the dorsal pathway, such as cerebral akinetopsia (for movement), or orientation agnosia (for the placement of objects in space). Focal brain injuries provide a unique opportunity to better understand regional brain function, particularly with the use of effective statistical approaches such as voxel-based lesion-symptom mapping (VLSM). The aim of the present work was twofold: (i) to review the various agnosia categories according to the traditional visual dual-pathway model; and (ii) to better assess the anatomical network underlying visual recognition through lesion-mapping studies correlating neuroanatomical and clinical outcomes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Electroretinography and Visual Evoked Potentials in Childhood Brain Tumor Survivors.

PubMed

Pietilä, Sari; Lenko, Hanna L; Oja, Sakari; Koivisto, Anna-Maija; Pietilä, Timo; Mäkipernaa, Anne

2016-07-01

This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment. © The Author(s) 2016.

Impact of Applying Sex Sorted Semen on the Selection Proportion of the Sire of Dams Selection Pathway in a Nucleus Program.

PubMed

Joezy-Shekalgorabi, Sahereh

2017-11-03

In a nucleus breeding scheme, the sire of dams pathway plays an important role in producing genetic improvement. Selection proportion is the key parameter for predicting selection intensity, through truncating the normal distribution. Semen sexing using flowcytometrie reduces the number of vials of sperm that can be obtained from a proved bull. In addition, a lower fertility of this kind of sperm is expected because of the lower sperm dosage in sex sorted semen. Both of these factors could affect the selection proportion in the sire of dams pathway (pSD). In the current study, through a deterministic simulation, effect of utilizing sex sorted semen on selection (pSD) was investigated in three different strategies including 1: continuous use of sex sorted semen in heifers (CS), 2: the use of sex sorted semen for the first two (S2) and 3: the first (S1) inseminations followed by conventional semen. Results indicated that the use of sex sorted semen has a negative impact on the sire of dams (SD) pathway due to increase in selection proportion. Consequently selection intensity was decreased by 10.24 to 20.57, 6.38 to 8.87 and 3.76 to 6.25 percent in the CS, S2 and S1 strategies, respectively. Considering the low effect of sexed semen on genetic improvement in dam pathways, it is necessary to consider the joint effect of using sex sorted semen on the sire and dams pathway to estimate about the real effect of sexed semen on genetic improvement in a nucleus breeding scheme.

Multivariate analysis and visualization of soil quality data for no-till systems.

PubMed

Villamil, M B; Miguez, F E; Bollero, G A

2008-01-01

To evidence the multidimensionality of the soil quality concept, we propose the use of data visualization as a tool for exploratory data analyses, model building, and diagnostics. Our objective was to establish the best edaphic indicators for assessing soil quality in four no-till systems with regard to functioning as a medium for crop production and nutrient cycling across two Illinois locations. The compared situations were no-till corn-soybean rotations including either winter fallowing (C/S) or cover crops of rye (Secale cereale; C-R/S-R), hairy vetch (Vicia villosa; C-R/S-V), or their mixture (C-R/S-VR). The dataset included the variables bulk density (BD), penetration resistance (PR), water aggregate stability (WAS), soil reaction (pH), and the contents of soil organic matter (SOM), total nitrogen (TN), soil nitrates (NO(3)-N), and available phosphorus (P). Interactive data visualization along with canonical discriminant analysis (CDA) allowed us to show that WAS, BD, and the contents of P, TN, and SOM have the greatest potential as soil quality indicators in no-till systems in Illinois. It was more difficult to discriminate among WCC rotations than to separate these from C/S, considerably inflating the error rate associated with CDA. We predict that observations of no-till C/S will be classified correctly 51% of the time, while observations of no-till WCC rotations will be classified correctly 74% of the time. High error rates in CDA underscore the complexity of no-till systems and the need in this area for more long-term studies with larger datasets to increase accuracy to acceptable levels.

Rapid Assessment of Avoidable Blindness and Diabetic Retinopathy in Gilan Province, Iran.

PubMed

Katibeh, Marzieh; Behboudi, Hassan; Moradian, Siamak; Alizadeh, Yousef; Beiranvand, Ramin; Sabbaghi, Hamideh; Ahmadieh, Hamid

2017-12-01

To conduct an assessment of avoidable blindness and diabetic retinopathy (DR) in Gilan, 2014. A cross-sectional population-based survey was performed on a representative sample of urban and rural individuals aged ≥50 years of the province. Blindness was defined as presenting visual acuity (PVA) <3/60 in the better eye. Moderate visual impairment (MVI) and severe visual impairment (SVI) were defined as 6/60 ≤ PVA <6/18 and 3/60 ≤ PVA <6/60 in the better eye, respectively. Diabetes mellitus (DM) was determined based on random blood sugar (RBS) levels ≥200 mg/dL or a previous diagnosis. We used the Scottish grading system to grade DR. We invited 2975 individuals from 85 clusters. Age- and sex-adjusted prevalence and 95% confidence interval (CI) of blindness, SVI, MVI, and DM in 2587 participants (response rate: 86.9%) were 1.5% (95% CI: 1.1-2.0), 1.5% (95% CI: 0.9-2.0), 11.3% (95% CI: 9.9-12.7) and 21.4% (95% CI: 19.2-23.7), respectively. The leading causes of blindness were cataract (47.1%), age-related macular degeneration (14.7%) and DR (8.8%). Cataract surgery (CS) coverage was 69.3%. The main challenges for CS were cost and unawareness. The outcome of CS was good in 66.9% of operated eyes. Any DR and/or maculopathy were observed in 25.3% (95% CI: 21.0-29.5) of subjects including 12.6% (95% CI: 9.7-15.6) sight-threatening DR. In previously known DM cases, 215 (41.7%) had never undergone an eye examination for DR. The proportion of avoidable blindness and DR is considerable in Gilan Province.

Protection of dopamine towards autoxidation reaction by encapsulation into non-coated- or chitosan- or thiolated chitosan-coated-liposomes.

PubMed

Trapani, A; Mandracchia, D; Tripodo, G; Cometa, S; Cellamare, S; De Giglio, E; Klepetsanis, P; Antimisiaris, S G

2018-05-26

The aim of this work is to evaluate the potential of non-coated-, chitosan-(CS)- or chitosan-glutathione conjugate- (CS-GSH)-coated liposomes to protect the neurotransmitter Dopamine (DA) from the autoxidation reaction in neutral/alkaline conditions. This may be of interest in the development of nanotechnology-based approaches to improve Parkinson's disease treatment because decreased ROS production and reduced DA associated neurotoxicity are expected. For the mentioned purposes, DA-loaded vesicles were prepared by the Dried Reconstituted Vesicles (DRV) method, and were subsequently coated using solutions of polycations. As for the mean diameters of liposomes so prepared, the CS-GSH coated liposomes showed a significant decrease in size compared to the corresponding non-coated and CS-coated vesicles. The surface charge of DA-loaded non-coated liposomes was -10.8 mV, whereas the CS or CS-GSH coated vesicles showed a slightly positive ζ-potential. The capability of the herein studied vesicles to prevent DA autoxidation was evaluated by visual inspection, monitoring DA/lipid ratio as such and under stressed conditions. The results suggest that liposome formulations partially protect the neurotransmitter from the autoxidation reaction. In particular, the CS-GSH coated liposomes were more stable than the corresponding CS-coated and non-coated ones against the oxidative damage and were found to deliver the neurotransmitter in a sustained manner. Probably, this is due to the localization of the neurotransmitter in the core of the vesicles as indicated by XPS which confirmed the absence of the neurotransmitter on the surface of these vesicles. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of Urinary Biomarkers for Internal Exposure by Cesium-137 Using a Metabolomics Approach in Mice

PubMed Central

Goudarzi, Maryam; Weber, Waylon; Mak, Tytus D.; Chung, Juijung; Doyle-Eisele, Melanie; Melo, Dunstana; Brenner, David J.; Guilmette, Raymond A.; Fornace, Albert J.

2014-01-01

Cesium-137 is a fission product of uranium and plutonium in nuclear reactors and is released in large quantities during nuclear explosions or detonation of an improvised device containing this isotope. This environmentally persistent radionuclide undergoes radioactive decay with the emission of beta particles as well as gamma radiation. Exposure to 137Cs at high doses can cause acute radiation sickness and increase risk for cancer and death. The serious health risks associated with 137Cs exposure makes it critical to understand how it affects human metabolism and whether minimally invasive and easily accessible samples such as urine and serum can be used to triage patients in case of a nuclear disaster or a radiologic event. In this study, we have focused on establishing a time-dependent metabolomic profile for urine collected from mice injected with 137CsCl. The samples were collected from control and exposed mice on days 2, 5, 20 and 30 after injection. The samples were then analyzed by ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC/TOFMS) and processed by an array of informatics and statistical tools. A total of 1,412 features were identified in ESI+ and ESI− modes from which 200 were determined to contribute significantly to the separation of metabolomic profiles of controls from those of the different treatment time points. The results of this study highlight the ease of use of the UPLC/TOFMS platform in finding urinary biomarkers for 137Cs exposure. Pathway analysis of the statistically significant metabolites suggests perturbations in several amino acid and fatty acid metabolism pathways. The results also indicate that 137Cs exposure causes: similar changes in the urinary excretion levels of taurine and citrate as seen with external-beam gamma radiation; causes no attenuation in the levels of hexanoylglycine and N-acetylspermidine; and has unique effects on the levels of isovalerylglycine and tiglylglycine. PMID:24377719

Involvement of endoplasmic reticulum in hepatitis B virus replication.

PubMed

Xia, Weiliang; Shen, Yan; Xie, Haiyang; Zheng, Shusen

2006-11-01

The mitochondrial calcium and downstream proline-rich tyrosine kinase-2 (PyK2) signaling pathway are critical to hepatitis B virus (HBV) replication, and the endoplasmic reticulum (ER) plays an important role in intracellular calcium regulation. To investigate the role of ER in HBV replication, the HBV genome transfected HepG2.2.15 cells were treated by cyclosporine A (CsA), cyclopiazonic acid (CPA), ryanodine and U73122, which are all specific blockers of calcium channels located in either ER or mitochondria. The HBV replication level was evaluated by two methods: slot blot hybridization analysis of intracellular HBV DNA and real-time polymerase chain reaction (PCR) analysis of secreted HBV DNA in supernatant; the activation of PyK2 kinase was detected by Western blot analysis. Results indicated that the HBV replication was inhibited when mitochondrial permeability transition pore, ER Ca2+ -ATPase and ER inositol 1,4,5-trisphosphate receptor (IP3R) were blocked by CsA, CPA and U73122, respectively; but not inhibited when ER ryanodine receptor was blocked by ryanodine. The PyK2 phosphorylation level declined after treatment of 2 microg/ml CsA, 5 microM CPA and 25 microM U73122, but not changed apparently after 50 microM ryanodine treatment. Compared with monotreatment, a more powerful inhibitory effect was achieved when the CsA, CPA and U73122 were combined used in twosome or triple manner, while the HBV replication level did not change apparently when ryanodine combined with CsA, CPA or U73122. In conclusion, besides the mitochondria, the ER also participates in the HBV replication through calcium-PyK2 signaling pathway; the calcium channels of ER Ca2+ -ATPase and ER IP3R are responsible for this role; during this complicated process, an interaction between ER and mitochondria maybe involved.

Disruption of SorCS2 reveals differences in the regulation of stereociliary bundle formation between hair cell types in the inner ear

PubMed Central

Taylor, Ruth R.; Lovett, Michael; Jagger, Daniel J.

2017-01-01

Behavioural anomalies suggesting an inner ear disorder were observed in a colony of transgenic mice. Affected animals were profoundly deaf. Severe hair bundle defects were identified in all outer and inner hair cells (OHC, IHC) in the cochlea and in hair cells of vestibular macular organs, but hair cells in cristae were essentially unaffected. Evidence suggested the disorder was likely due to gene disruption by a randomly inserted transgene construct. Whole-genome sequencing identified interruption of the SorCS2 (Sortilin-related VPS-10 domain containing protein) locus. Real-time-qPCR demonstrated disrupted expression of SorCS2 RNA in cochlear tissue from affected mice and this was confirmed by SorCS2 immuno-labelling. In all affected hair cells, stereocilia were shorter than normal, but abnormalities of bundle morphology and organisation differed between hair cell types. Bundles on OHC were grossly misshapen with significantly fewer stereocilia than normal. However, stereocilia were organised in rows of increasing height. Bundles on IHC contained significantly more stereocilia than normal with some longer stereocilia towards the centre, or with minimal height differentials. In early postnatal mice, kinocilia (primary cilia) of IHC and of OHC were initially located towards the lateral edge of the hair cell surface but often became surrounded by stereocilia as bundle shape and apical surface contour changed. In macular organs the kinocilium was positioned in the centre of the cell surface throughout maturation. There was disruption of the signalling pathway controlling intrinsic hair cell apical asymmetry. LGN and Gαi3 were largely absent, and atypical Protein Kinase C (aPKC) lost its asymmetric distribution. The results suggest that SorCS2 plays a role upstream of the intrinsic polarity pathway and that there are differences between hair cell types in the deployment of the machinery that generates a precisely organised hair bundle. PMID:28346477

Visual Performance of a Quadrifocal (Trifocal) Intraocular Lens Following Removal of the Crystalline Lens.

PubMed

Kohnen, Thomas; Herzog, Michael; Hemkeppler, Eva; Schönbrunn, Sabrina; De Lorenzo, Nina; Petermann, Kerstin; Böhm, Myriam

2017-12-01

To evaluate visual performance after implantation of a quadrifocal intraocular lens (IOL). Setting: Department of Ophthalmology, Goethe University, Frankfurt, Germany. Twenty-seven patients (54 eyes) received bilateral implantation of the PanOptix IOL (AcrySof IQ PanOptixTM; Alcon Research, Fort Worth, Texas, USA) pre-enrollment. Exclusion criteria were previous ocular surgeries, corneal astigmatism of >1.5 diopter (D), ocular pathologies, or corneal abnormalities. Intervention or Observational Procedure(s): Postoperative examination at 3 months including manifest refraction; uncorrected visual acuity (UCVA) and distance-corrected visual acuity (DCVA) in 4 m, 80 cm, 60 cm, and 40 cm slit-lamp examination; defocus testing; contrast sensitivity (CS) under photopic and mesopic conditions; and a questionnaire on subjective quality of vision, optical phenomena, and spectacle independence was performed. At 3 months postoperatively, UCVA and DCVA in 4 m, 80 cm, 60 cm, and 40 cm (logMAR), defocus curves, CS, and quality-of-vision questionnaire results. Mean spherical equivalent was -0.04 ± 0.321 D 3 months postoperatively. Binocular UCVA at distance, intermediate (80 cm, 60 cm), and near was 0.00 ± 0.094 logMAR, 0.09 ± 0.107 logMAR, 0.00 ± 0.111 logMAR, and 0.01 ± 0.087 logMAR, respectively. Binocular defocus curve showed peaks with best visual acuity (VA) at 0.00 D (-0.07 logMAR) and -2.00 D (-0.02 logMAR). Visual performance of the PanOptix IOL showed good VA at all distances; particularly good intermediate VA (logMAR > 0.1), with best VA at 60 cm; and high patient satisfaction and spectacle independence 3 months postoperatively. Copyright © 2017 Elsevier Inc. All rights reserved.

CsFe3(SeO3)2F6 with S = 5/2 Cube Tile Lattice.

PubMed

Lu, Hongcheng; Kageyama, Hiroshi

2018-05-21

A layered iron selenite fluoride CsFe 3 (SeO 3 ) 2 F 6 1 was hydrothermally synthesized. Single-crystal X-ray diffraction studies show that 1 has a trigonal ( P3̅ m1) lattice, where [Fe 3 (SeO 3 ) 2 F 6 ] - blocks of three iron sublayers are separated by Cs cations. Within the block, only Fe(2)F 6 and Fe(1)O 3 F 3 octahedra are magnetically connected via superexchange Fe(1) -F -Fe(2) pathways, giving an S = 5/2 cube tile (dice) lattice. At low magnetic field, 1 exhibits an antiferromagnetic transition at ∼130 K, where ferrimagnetic cube tile layers are arranged in a staggered manner. At low temperatures, we observed a field-induced transition to a ferrimagnetic state with a one-third magnetization plateau.

Antiferromagnetic S=1/2 spin chain driven by p-orbital ordering in CsO2.

PubMed

Riyadi, Syarif; Zhang, Baomin; de Groot, Robert A; Caretta, Antonio; van Loosdrecht, Paul H M; Palstra, Thomas T M; Blake, Graeme R

2012-05-25

We demonstrate, using a combination of experiment and density functional theory, that orbital ordering drives the formation of a one-dimensional (1D) S=1/2 antiferromagnetic spin chain in the 3D rocksalt structure of cesium superoxide (CsO2). The magnetic superoxide anion (O2(-)) exhibits degeneracy of its 2p-derived molecular orbitals, which is lifted by a structural distortion on cooling. A spin chain is then formed by zigzag ordering of the half-filled superoxide orbitals, promoting a superexchange pathway mediated by the p(z) orbitals of Cs(+) along only one crystal direction. This scenario is analogous to the 3d-orbital-driven spin chain found in the perovskite KCuF3 and is the first example of an inorganic quantum spin system with unpaired p electrons.

Cellular Cholesterol Accumulation Facilitates Ubiquitination and Lysosomal Degradation of Cell Surface-Resident ABCA1.

PubMed

Mizuno, Tadahaya; Hayashi, Hisamitsu; Kusuhara, Hiroyuki

2015-06-01

By excreting cellular cholesterol to apolipoprotein A-I, ATP-binding cassette transporter A1 (ABCA1) mediates the biogenesis of high-density lipoprotein in hepatocytes and prevents foam cell formation from macrophages. We recently showed that cell surface-resident ABCA1 (csABCA1) undergoes ubiquitination and later lysosomal degradation through the endosomal sorting complex required for transport system. Herein, we investigated the relevance of this degradation pathway to the turnover of csABCA1 in hypercholesterolemia. Immunoprecipitation and cell surface-biotinylation studies with HepG2 cells and mouse peritoneal macrophages showed that the ubiquitination level and degradation of csABCA1 were facilitated by treatment with a liver X receptor (LXR) agonist and acetylated low-density lipoprotein. The effects of an LXR agonist and acetylated low-density lipoprotein on the degradation of csABCA1 were repressed completely by treatment with bafilomycin, an inhibitor of lysosomal degradation, and by depletion of tumor susceptibility gene 101, a major component of endosomal sorting complex required for transport-I. RNAi analysis indicated that LXRβ inhibited the accelerated lysosomal degradation of csABCA1 by the LXR agonist, regardless of its transcriptional activity. Cell surface coimmunoprecipitation with COS1 cells expressing extracellularly hemagglutinin-tagged ABCA1 showed that LXRβ interacted with csABCA1 and inhibited the ubiquitination of csABCA1. Immunoprecipitates with anti-ABCA1 antibodies from the liver plasma membranes showed less LXRβ and a higher ubiquitination level of ABCA1 in high-fat diet-fed mice than in normal chow-fed mice. Under conditions of high cellular cholesterol content, csABCA1 became susceptible to ubiquitination by dissociation of LXRβ from csABCA1, which facilitated the lysosomal degradation of csABCA1 through the endosomal sorting complex required for transport system. © 2015 American Heart Association, Inc.

Oncofetal Chondroitin Sulfate Glycosaminoglycans Are Key Players in Integrin Signaling and Tumor Cell Motility.

PubMed

Clausen, Thomas Mandel; Pereira, Marina Ayres; Al Nakouzi, Nader; Oo, Htoo Zarni; Agerbæk, Mette Ø; Lee, Sherry; Ørum-Madsen, Maj Sofie; Kristensen, Anders Riis; El-Naggar, Amal; Grandgenett, Paul M; Grem, Jean L; Hollingsworth, Michael A; Holst, Peter J; Theander, Thor; Sorensen, Poul H; Daugaard, Mads; Salanti, Ali

2016-12-01

Many tumors express proteoglycans modified with oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS), which are normally restricted to the placenta. However, the role of ofCS in cancer is largely unknown. The function of ofCS in cancer was analyzed using the recombinant ofCS-binding VAR2CSA protein (rVAR2) derived from the malaria parasite, Plasmodium falciparum We demonstrate that ofCS plays a key role in tumor cell motility by affecting canonical integrin signaling pathways. Binding of rVAR2 to tumor cells inhibited the interaction of cells with extracellular matrix (ECM) components, which correlated with decreased phosphorylation of Src kinase. Moreover, rVAR2 binding decreased migration, invasion, and anchorage-independent growth of tumor cells in vitro Mass spectrometry of ofCS-modified proteoglycan complexes affinity purified from tumor cell lines on rVAR2 columns revealed an overrepresentation of proteins involved in cell motility and integrin signaling, such as integrin-β1 (ITGB1) and integrin-α4 (ITGA4). Saturating concentrations of rVAR2 inhibited downstream integrin signaling, which was mimicked by knockdown of the core chondroitin sulfate synthesis enzymes β-1,3-glucuronyltransferase 1 (B3GAT1) and chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1). The ofCS modification was highly expressed in both human and murine metastatic lesions in situ and preincubation or early intravenous treatment of tumor cells with rVAR2 inhibited seeding and spreading of tumor cells in mice. This was associated with a significant increase in survival of the animals. These data functionally link ofCS modifications with cancer cell motility and further highlights ofCS as a novel therapeutic cancer target. The cancer-specific expression of ofCS aids in metastatic phenotypes and is a candidate target for therapy. Mol Cancer Res; 14(12); 1288-99. ©2016 AACR. ©2016 American Association for Cancer Research.

Chlorella sorokiniana induces mitochondrial-mediated apoptosis in human non-small cell lung cancer cells and inhibits xenograft tumor growth in vivo.

PubMed

Lin, Ping-Yi; Tsai, Ching-Tsan; Chuang, Wan-Ling; Chao, Ya-Hsuan; Pan, I-Horng; Chen, Yu-Kuo; Lin, Chi-Chen; Wang, Bing-Yen

2017-02-01

Lung cancer is one of the leading causes of cancer related deaths worldwide. Marine microalgae are a source of biologically active compounds and are widely consumed as a nutritional supplement in East Asian countries. It has been reported that Chlorella or Chlorella extracts have various beneficial pharmacological compounds that modulate immune responses; however, no studies have investigated the anti-cancer effects of Chlorella sorokiniana (CS) on non-small cell lung cancer (NSCLC). In this study, we evaluated the anti-cancer effects of CS in two human NSCLC cell lines (A549 and CL1-5 human lung adenocarcinoma cells), and its effects on tumor growth in a subcutaneous xenograft tumor model. We also investigated the possible molecular mechanisms governing the pharmacological function of CS. Our results showed that exposure of the two cell lines to CS resulted in a concentration-dependent reduction in cell viability. In addition, the percentage of apoptotic cells increased in a dose-dependent manner, suggesting that CS might induce apoptosis in human NSCLC cells. Western blot analysis revealed that exposure to CS resulted in increased protein expression of the cleaved/activated forms of caspase-3, caspase-9, and PARP, except caspase-8. ZDEVD (caspase-3 inhibitor) and Z-LEHD (caspase-9 inhibitor) were sufficient at preventing apoptosis in both A549 and CL1-5 cells, proving that CS induced cell death via the mitochondria-mediated apoptotic pathway. Exposure of A549 and CL1-5 cells to CS for 24 h resulted in decreased expression of Bcl-2 protein and increased expression of Bax protein as well as decreased expression of two IAP family proteins, survivin and XIAP. We demonstrated that CS induces mitochondrial-mediated apoptosis in NSCLC cells via downregulation of Bcl-2, XIAP and survivin. In addition, we also found that the tumors growth of subcutaneous xenograft in vivo was markedly inhibited after oral intake of CS.

Sequence Analysis and Molecular Characterization of Clonorchis sinensis Hexokinase, an Unusual Trimeric 50-kDa Glucose-6-Phosphate-Sensitive Allosteric Enzyme

PubMed Central

Chen, Tingjin; Ning, Dan; Sun, Hengchang; Li, Ran; Shang, Mei; Li, Xuerong; Wang, Xiaoyun; Chen, Wenjun; Liang, Chi; Li, Wenfang; Mao, Qiang; Li, Ye; Deng, Chuanhuan; Wang, Lexun; Wu, Zhongdao; Huang, Yan; Xu, Jin; Yu, Xinbing

2014-01-01

Clonorchiasis, which is induced by the infection of Clonorchis sinensis (C. sinensis), is highly associated with cholangiocarcinoma. Because the available examination, treatment and interrupting transmission provide limited opportunities to prevent infection, it is urgent to develop integrated strategies to prevent and control clonorchiasis. Glycolytic enzymes are crucial molecules for trematode survival and have been targeted for drug development. Hexokinase of C. sinensis (CsHK), the first key regulatory enzyme of the glycolytic pathway, was characterized in this study. The calculated molecular mass (Mr) of CsHK was 50.0 kDa. The obtained recombinant CsHK (rCsHK) was a homotrimer with an Mr of approximately 164 kDa, as determined using native PAGE and gel filtration. The highest activity was obtained with 50 mM glycine-NaOH at pH 10 and 100 mM Tris-HCl at pH 8.5 and 10. The kinetics of rCsHK has a moderate thermal stability. Compared to that of the corresponding negative control, the enzymatic activity was significantly inhibited by praziquantel (PZQ) and anti-rCsHK serum. rCsHK was homotropically and allosterically activated by its substrates, including glucose, mannose, fructose, and ATP. ADP exhibited mixed allosteric effect on rCsHK with respect to ATP, while inorganic pyrophosphate (PPi) displayed net allosteric activation with various allosteric systems. Fructose behaved as a dose-dependent V activator with the substrate glucose. Glucose-6-phosphate (G6P) displayed net allosteric inhibition on rCsHK with respect to ATP or glucose with various allosteric systems in a dose-independent manner. There were differences in both mRNA and protein levels of CsHK among the life stages of adult worm, metacercaria, excysted metacercaria and egg of C. sinensis, suggesting different energy requirements during different development stages. Our study furthers the understanding of the biological functions of CsHK and supports the need to screen for small molecule inhibitors of CsHK to interfere with glycolysis in C. sinensis. PMID:25232723

Precursor routes to quaternary intermetallics: Synthesis, crystal structure, and physical properties of clathrate-II Cs{sub 8}Na{sub 16}Al{sub 24}Si{sub 112}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, Kaya; Dong, Yongkwan; Nolas, George S., E-mail: gnolas@usf.edu

A new quaternary clathrate–II composition, Cs{sub 8}Na{sub 16}Al{sub 24}Si{sub 112}, was synthesized by kinetically controlled thermal decomposition (KCTD) employing both NaSi and NaAlSi as the precursors and CsCl as a reactive flux. The crystal structure and composition of Cs{sub 8}Na{sub 16}Al{sub 24}Si{sub 112} were investigated using both Rietveld refinement and elemental analysis, and the temperature dependent transport properties were investigated. Our results indicate that KCTD with multiple precursors is an effective method for the synthesis of multinary inorganic phases that are not easily accessible by traditional solid-state synthesis or crystal growth techniques. - Graphical abstract: Quaternary Cs{sub 8}Na{sub 16}Al{sub 24}S{submore » 112} clathrate–II was synthesized for the first time by kinetically controlled thermal decomposition (KCTD) employing a NaSi+NaAlSi precursor mixture with CsCl as the reactive flux, and the structural and transport properties were investigated. Our approach demonstrates a new synthetic pathway for the synthesis of multinary inorganic compounds. This work reports the exploration of a new clathrate composition as this class of materials continues to be of interest for thermoelectrics and other energy-related applications.« less

Silibinin Inhibits Neutrophilic Inflammation and Mucus Secretion Induced by Cigarette Smoke via Suppression of ERK-SP1 Pathway.

PubMed

Park, Ji-Won; Shin, Na-Rae; Shin, In-Sik; Kwon, Ok-Kyoung; Kim, Joong-Sun; Oh, Sei-Ryang; Kim, Jae-Hong; Ahn, Kyung-Seop

2016-12-01

Silibinin, the main ingredient of silymarin, has been used as a traditional drug for over 2000 years to treat a range of liver diseases. Recent studies have also demonstrated that silibinin possesses antiinflammatory and anticancer properties. In the study, we researched the efficacy of silibinin on the development of COPD using a cigarette smoke (CS)-induced and lipopolysaccharide (LPS)-induced COPD model mice and stimulation of NCI-H292 cells with CS condensate. Silibinin was administered to mice by oral gavage 1 h before CS exposure for 10 days. In in vitro experiment, we evaluated the effect of silibinin on the expression of MUC5AC in H292 cells stimulated with CS condensate. Furthermore, silibinin suppressed the CS and LPS treatment-induced extracellular signal-regulated kinase (ERK) phosphorylation and SP-1 expression. Silibinin also decreased airway inflammation and reduced the expression of MUC5AC and myeloperoxidase. Furthermore, co-treatment with silibinin and ERK inhibitors considerably decreased the levels of pro-inflammatory mediators, ERK phosphorylation, and SP-1 expression. Taken together, the results indicate that silibinin effectively suppressed the neutrophilic airway inflammation provoked by treatment with LPS and CS, which was closely associated with downregulation of ERK phosphorylation. Therefore, our searching offers that silibinin has a remedical probable for COPD disease. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Feature-Specific Organization of Feedback Pathways in Mouse Visual Cortex.

PubMed

Huh, Carey Y L; Peach, John P; Bennett, Corbett; Vega, Roxana M; Hestrin, Shaul

2018-01-08

Higher and lower cortical areas in the visual hierarchy are reciprocally connected [1]. Although much is known about how feedforward pathways shape receptive field properties of visual neurons, relatively little is known about the role of feedback pathways in visual processing. Feedback pathways are thought to carry top-down signals, including information about context (e.g., figure-ground segmentation and surround suppression) [2-5], and feedback has been demonstrated to sharpen orientation tuning of neurons in the primary visual cortex (V1) [6, 7]. However, the response characteristics of feedback neurons themselves and how feedback shapes V1 neurons' tuning for other features, such as spatial frequency (SF), remain largely unknown. Here, using a retrograde virus, targeted electrophysiological recordings, and optogenetic manipulations, we show that putatively feedback neurons in layer 5 (hereafter "L5 feedback") in higher visual areas, AL (anterolateral area) and PM (posteromedial area), display distinct visual properties in awake head-fixed mice. AL L5 feedback neurons prefer significantly lower SF (mean: 0.04 cycles per degree [cpd]) compared to PM L5 feedback neurons (0.15 cpd). Importantly, silencing AL L5 feedback reduced visual responses of V1 neurons preferring low SF (mean change in firing rate: -8.0%), whereas silencing PM L5 feedback suppressed responses of high-SF-preferring V1 neurons (-20.4%). These findings suggest that feedback connections from higher visual areas convey distinctly tuned visual inputs to V1 that serve to boost V1 neurons' responses to SF. Such like-to-like functional organization may represent an important feature of feedback pathways in sensory systems and in the nervous system in general. Copyright © 2017 Elsevier Ltd. All rights reserved.

Measuring Quadriceps strength in adults with severe or moderate intellectual and visual disabilities: Feasibility and reliability.

PubMed

Dijkhuizen, Annemarie; Douma, Rob K; Krijnen, Wim P; van der Schans, Cees P; Waninge, Aly

2018-05-30

A feasible and reliable instrument to measure strength in persons with severe intellectual and visual disabilities (SIVD) is lacking. The aim of our study was to determine feasibility, learning period and reliability of three strength tests. Twenty-nine participants with SIVD performed the Minimum Sit-to-Stand Height test (MSST), the Leg Extension test (LE) and the 30 seconds Chair-Stand test (30sCS), once per week for 5 weeks. Feasibility was determined by the percentage of successful measurements; learning effect by using paired t test between two consecutive measurements; test-retest reliability by intraclass correlation coefficient and Limits of Agreement and, correlations by Pearson correlations. A sufficient feasibility and learning period of the tests was shown. The methods had sufficient test-retest reliability and moderate-to-sufficient correlations. The MSST, the LE, and the 30sCS are feasible tests for measuring muscle strength in persons with SIVD, having sufficient test re-test reliability. © 2018 John Wiley & Sons Ltd.

In situ synthesis of nanocomposite membranes: comprehensive improvement strategy for direct methanol fuel cells.

PubMed

Rao, Siyuan; Xiu, Ruijie; Si, Jiangju; Lu, Shanfu; Yang, Meng; Xiang, Yan

2014-03-01

In situ synthesis is a powerful approach to control nanoparticle formation and consequently confers extraordinary properties upon composite membranes relative to conventional doping methods. Herein, uniform nanoparticles of cesium hydrogen salts of phosphotungstic acid (CsPW) are controllably synthesized in situ in Nafion to form CsPW–Nafion nanocomposite membranes with both improved proton conductivity and methanol-crossover suppression. A 101.3% increase of maximum power density has been achieved relative to pristine Nafion in a direct methanol fuel cell (DMFC), indicating a potential pathway for large-scale fabrication of DMFC alternative membranes.

Neural Pathways Conveying Novisual Information to the Visual Cortex

PubMed Central

2013-01-01

The visual cortex has been traditionally considered as a stimulus-driven, unimodal system with a hierarchical organization. However, recent animal and human studies have shown that the visual cortex responds to non-visual stimuli, especially in individuals with visual deprivation congenitally, indicating the supramodal nature of the functional representation in the visual cortex. To understand the neural substrates of the cross-modal processing of the non-visual signals in the visual cortex, we firstly showed the supramodal nature of the visual cortex. We then reviewed how the nonvisual signals reach the visual cortex. Moreover, we discussed if these non-visual pathways are reshaped by early visual deprivation. Finally, the open question about the nature (stimulus-driven or top-down) of non-visual signals is also discussed. PMID:23840972

Outcomes of Aggressive Surgical Resection in Growth Hormone-Secreting Pituitary Adenomas with Cavernous Sinus Invasion.

PubMed

Park, Hun Ho; Kim, Eui Hyun; Ku, Cheol Ryong; Lee, Eun Jig; Kim, Sun Ho

2018-06-12

Cavernous sinus (CS) invasion is an unfavorable factor hindering remission of growth hormone (GH)-secreting pituitary adenomas. However, few data exist on aggressive surgical resection. The authors investigate the role of CS exploration for GH-secreting pituitary adenomas with CS invasion. We classified 132 patients with GH-secreting pituitary adenomas invading CS into 4 groups. The patients underwent surgery using a microsurgical transsphenoidal approach (TSA) with assistance of an endoscope. For adenomas with CS invasion confined to the medial compartment of ICA (internal carotid artery), they were divided into type A (without radiological evidence) and B (with radiological evidence). For adenomas with ICA encasement, tumors were divided according to the surgical approach: type C (standard TSA) and D (far-lateral TSA). Surgical and endocrinologic outcomes were compared between each group. Gross total resection rates were 100%, 73.6%, 14.7%, 0% and endocrinologic remission rates by surgery alone were 100% , 62.3%, 26.5%, 0% for type A, B, C, and D tumors, respectively. There was no endocrinologic remission by surgery alone for type D tumors. Nevertheless, it showed marked reduction of postoperative nadir GH at 1 week, 6 months, 1 year, and IGF-I at 1 year compared to type C tumors. For tumors with CS invasion confined to the medial compartment of ICA, total resection should be attempted by direct visualization of the entire medial wall of CS. Even for tumors with ICA encasement, aggressive tumor resection by far-lateral TSA can increase the chance of remission with the help of adjuvant treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Adaptability to pain is associated with potency of local pain inhibition, but not conditioned pain modulation: a healthy human study.

PubMed

Zheng, Zhen; Wang, Kelun; Yao, Dongyuan; Xue, Charlie C L; Arendt-Nielsen, Lars

2014-05-01

This study investigated the relationship between pain sensitivity, adaptability, and potency of endogenous pain inhibition, including conditioned pain modulation (CPM) and local pain inhibition. Forty-one healthy volunteers (20 male, 21 female) received conditioning stimulation (CS) over 2 sessions in a random order: tonic heat pain (46 °C) on the right leg for 7 minutes and cold pressor pain (1 °C to 4 °C) on the left hand for 5 minutes. Participants rated the intensity of pain continuously using a 0 to 10 electronic visual analogue scale. The primary outcome measures were pressure pain thresholds (PPT) measured at the heterotopic and homotopic location to the CS sites before, during, and 20 minutes after CS. Two groups of participants, pain adaptive and pain nonadaptive, were identified based on their response to pain in the cold pressor test. Pain-adaptive participants showed a pain reduction between peak pain and pain at end of the test by at least 2 of 10 (n=16); whereas the pain-nonadaptive participants reported unchanged peak pain during 5-minute CS (n=25). Heterotopic PPTs during the CS did not differ between the 2 groups. However, increased homotopic PPTs measured 20 minutes after CS correlated with the amount of pain reduction during CS. These results suggest that individual sensitivity and adaptability to pain does not correlate with the potency of CPM. Adaptability to pain is associated with longer-lasting local pain inhibition. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Elaboration of the Visual Pathways from the Study of War-Related Cranial Injuries: The Period from the Russo-Japanese War to World War I.

PubMed

Lanska, Douglas J

2016-01-01

As a result of the wars in the early 20th century, elaboration of the visual pathways was greatly facilitated by the meticulous study of visual defects in soldiers who had suffered focal injuries to the visual cortex. Using relatively crude techniques, often under difficult wartime circumstances, investigators successfully mapped key features of the visual pathways. Studies during the Russo- Japanese War (1904-1905) by Tatsuji Inouye (1881-1976) and during World War I by Gordon Holmes (1876-1965), William Lister (1868-1944), and others produced increasingly refined retinotopic maps of the primary visual cortex, which were later supported and refined by studies during and after World War II. Studies by George Riddoch (1888-1947) during World War I also demonstrated that some patients could still perceive motion despite blindness caused by damage to their visual cortex and helped to establish the concept of functional partitioning of visual processes in the occipital cortex. © 2016 S. Karger AG, Basel.

Behaviour of oceanic 137Cs following the Fukushima Daiichi Nuclear Power Plant accident for four years simulated numerically by a regional ocean model

NASA Astrophysics Data System (ADS)

Tsumune, D.; Tsubono, T.; Aoyama, M.; Misumi, K.; Tateda, Y.

2015-12-01

A series of accidents at the Fukushima Dai-ichi Nuclear Power Plant (1F NPP) following the earthquake and tsunami of 11 March 2011 resulted in the release of radioactive materials to the ocean by two major pathways, direct release from the accident site and atmospheric deposition.We reconstructed spatiotemporal variability of 137Cs activity in the regional ocean for four years by numerical model, such as a regional scale and the North Pacific scale oceanic dispersion models, an atmospheric transport model, a sediment transport model, a dynamic biological compartment model for marine biota and river runoff model. Direct release rate of 137Cs were estimated for four years after the accident by comparing simulated results and observed activities very close to the site. The estimated total amounts of directly release was 3.6±0.7 PBq. Directly release rate of 137Cs decreased exponentially with time by the end of December 2012 and then, was almost constant. Decrease rate were quite small after 2013. The daily release rate of 137Cs was estimated to be the order of magnitude of 1010 Bq/day by the end of March 2015. The activity of directly released 137Cs was detectable only in the coastal zone after December 2012. Simulated 137Cs activities attributable to direct release were in good agreement with observed activities, a result that implies the estimated direct release rate was reasonable. There is no observed data of 137Cs activity in the ocean from 11 to 21 March 2011. Observed data of marine biota should reflect the history of 137Cs activity in this early period. We reconstructed the history of 137Cs activity in this early period by considering atmospheric deposition, river input, rain water runoff from the 1F NPP site. The comparisons between simulated 137Cs activity of marine biota by a dynamic biological compartment and observed data also suggest that simulated 137Cs activity attributable to atmospheric deposition was underestimated in this early period. The simulated river flux of 137Cs to the ocean did not effect on 137Cs activity in the ocean even if the parameters in this simulation have uncertainties because of the lack of observed data in rivers in the earlier period.

Behaviour of oceanic 137Cs following the Fukushima Daiichi Nuclear Power Plant accident for four years simulated numerically by a regional ocean model

NASA Astrophysics Data System (ADS)

Torn, M. S.; Koven, C. D.; Riley, W. J.; Zhu, B.; Hicks Pries, C.; Phillips, C. L.

2014-12-01

A series of accidents at the Fukushima Dai-ichi Nuclear Power Plant (1F NPP) following the earthquake and tsunami of 11 March 2011 resulted in the release of radioactive materials to the ocean by two major pathways, direct release from the accident site and atmospheric deposition.We reconstructed spatiotemporal variability of 137Cs activity in the regional ocean for four years by numerical model, such as a regional scale and the North Pacific scale oceanic dispersion models, an atmospheric transport model, a sediment transport model, a dynamic biological compartment model for marine biota and river runoff model. Direct release rate of 137Cs were estimated for four years after the accident by comparing simulated results and observed activities very close to the site. The estimated total amounts of directly release was 3.6±0.7 PBq. Directly release rate of 137Cs decreased exponentially with time by the end of December 2012 and then, was almost constant. Decrease rate were quite small after 2013. The daily release rate of 137Cs was estimated to be the order of magnitude of 1010 Bq/day by the end of March 2015. The activity of directly released 137Cs was detectable only in the coastal zone after December 2012. Simulated 137Cs activities attributable to direct release were in good agreement with observed activities, a result that implies the estimated direct release rate was reasonable. There is no observed data of 137Cs activity in the ocean from 11 to 21 March 2011. Observed data of marine biota should reflect the history of 137Cs activity in this early period. We reconstructed the history of 137Cs activity in this early period by considering atmospheric deposition, river input, rain water runoff from the 1F NPP site. The comparisons between simulated 137Cs activity of marine biota by a dynamic biological compartment and observed data also suggest that simulated 137Cs activity attributable to atmospheric deposition was underestimated in this early period. The simulated river flux of 137Cs to the ocean did not effect on 137Cs activity in the ocean even if the parameters in this simulation have uncertainties because of the lack of observed data in rivers in the earlier period.

'What' Is Happening in the Dorsal Visual Pathway.

PubMed

Freud, Erez; Plaut, David C; Behrmann, Marlene

2016-10-01

The cortical visual system is almost universally thought to be segregated into two anatomically and functionally distinct pathways: a ventral occipitotemporal pathway that subserves object perception, and a dorsal occipitoparietal pathway that subserves object localization and visually guided action. Accumulating evidence from both human and non-human primate studies, however, challenges this binary distinction and suggests that regions in the dorsal pathway contain object representations that are independent of those in ventral cortex and that play a functional role in object perception. We review here the evidence implicating dorsal object representations, and we propose an account of the anatomical organization, functional contributions, and origins of these representations in the service of perception. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluative conditioning increases with temporal contiguity. The influence of stimulus order and stimulus interval on evaluative conditioning.

PubMed

Gast, Anne; Langer, Sebastian; Sengewald, Marie-Ann

2016-10-01

Evaluative conditioning (EC) is a change in valence that is due to pairing a conditioned stimulus (CS) with another, typically valent, unconditioned stimulus (US). This paper investigates how basic presentation parameters moderate EC effects. In two studies we tested the effectiveness of different temporal relations of the CS and the US, that is, the order in which the stimuli were presented and the temporal distance between them. Both studies showed that the size of EC effects was independent of the presentation order of CS and US within a stimulus pair. Contrary to classical conditioning effects, EC effects are thus not most pronounced after CS-first presentations. Furthermore, as shown in Experiment 2, EC effects increased in magnitude as the temporal interval between CS and US presentations decreased. Experiment 1 showed largest EC effects in the condition with simultaneous presentations - which can be seen as the condition with the temporally closest presentation. In this Experiment stimuli were presented in two different modalities, which might have facilitated simultaneous processing. In Experiment 2, in which all stimuli were presented visually, this advantage of simultaneous presentation was not found. We discuss practical and theoretical implications of our findings. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel vehicle for local protein delivery to the inner ear: injectable and biodegradable thermosensitive hydrogel loaded with PLGA nanoparticles.

PubMed

Dai, Juan; Long, Wei; Liang, Zhongping; Wen, Lu; Yang, Fan; Chen, Gang

2018-01-01

Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2 b (IFN α-2 b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37 °C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy.

Procarcinogenic effects of cyclosporine A are mediated through the activation of TAK1/TAB1 signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Jianmin; Walsh, Stephanie B.; Verney, Zoe M.

Research highlights: {yields} Organ transplant recipients are highly susceptible to early skin cancer development. {yields} CsA-mediated TGFB1-dependent TAK1/TAB1 signaling augments invasive tumor growth. {yields} CsA enhances accumulation of upstream kinases, ZMP, AMPK and IRAK to activate TAK1. {yields} TAK1 mediates enhanced proliferation and reduced apoptosis via CsA-dependent NF{kappa}B. -- Abstract: Cyclosporine A (CsA) is an immunosuppressive drug commonly used for maintaining chronic immune suppression in organ transplant recipients. It is known that patients receiving CsA manifest increased growth of aggressive non-melanoma skin cancers. However, the underlying mechanism by which CsA augments tumor growth is not fully understood. Here, we showmore » that CsA augments the growth of A431 epidermoid carcinoma xenograft tumors by activating tumor growth factor {beta}-activated kinase1 (TAK1). The activation of TAK1 by CsA occurs at multiple levels by kinases ZMP, AMPK and IRAK. TAK1 forms heterodimeric complexes with TAK binding protein 1 and 2 (TAB1/TAB2) which in term activate nuclear factor {kappa}B (NF{kappa}B) and p38 MAP kinase. Transcriptional activation of NF{kappa}B is evidenced by IKK{beta}-mediated phosphorylation-dependent degradation of I{kappa}B and consequent nuclear translocation of p65. This also leads to enhancement in the expression of its transcriptional target genes cyclin D1, Bcl2 and COX-2. Similarly, activation of p38 leads to enhanced inflammation-related signaling shown by increased phosphorylation of MAPKAPK2 and which in turn phosphorylates its substrate HSP27. Activation of both NF{kappa}B and p38 MAP kinase provide mitogenic stimuli to augment the growth of SCCs.« less

Development of a novel CsA-PLGA drug delivery system based on a glaucoma drainage device for the prevention of postoperative fibrosis.

PubMed

Dai, Zhaoxing; Yu, Xiaobo; Hong, Jiaxu; Liu, Xi; Sun, Jianguo; Sun, Xinghuai

2016-09-01

The formation of a scar after glaucoma surgery often leads to unsuccessful control of intraocular pressure, and should be prevented by using a variety of methods. We designed and developed a novel drug delivery system (DDS) comprising cyclosporine A (CsA) and poly(lactic-co-glycolic acid) (PLGA) based on a glaucoma drainage device (GDD) that can continuously release CsA to prevent postoperative fibrosis following glaucoma surgery. The CsA@PLGA@GDD DDS was observed by field emission scanning electron microscopy and revealed an asymmetric pore structure. Thermogravimetric analysis was performed to measure the weight loss and evaluate the thermal stability of the CsA@PLGA@GDD DDS. The in vitro drug release profile of the DDS was studied using high performance liquid chromatography, which confirmed that the DDS released CsA at a stable rate and maintained adequate CsA concentrations for a relatively long time. The biocompatibility of the DDS and the inhibitory effects on the postoperative fibrosis were investigated in vitro using rabbit Tenon's fibroblasts. The in vivo safety and efficacy of the DDS were examined by implanting the DDS into Tenon's capsules in New Zealand rabbits. Bleb morphology, intraocular pressure, anterior chamber reactions, and anterior chamber angiography were studied at a series of set times. The DDS kept the filtration pathway unblocked for a longer time compared with the control GDD. The results indicate that the CsA@PLGA@GDD DDS represents a safe and effective strategy for preventing scar formation after glaucoma surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

Attenuation of cyclosporine A toxicity by sublethal heat shock. Role of catalase.

PubMed

Andrés, David; Bautista, Mirandeli; Cascales, María

2005-02-01

Cyclosporine A (CsA) is the immunosuppressor most frequently used in transplant surgery and in the treatment of autoimmune diseases because of its specific inhibiting effect on signal transduction pathways of cell T receptor. It has been shown that CsA is able to generate reactive oxygen species and lipid peroxidation, which are directly involved in the CsA hepatotoxicity. In the present study, we investigated the effect of a sublethal heat pre-treatment (43 degrees C for 30 min) on the hepatoma cell line HepG2 exposed to cytotoxic concentrations of CsA (10 and 25 microM) for 3 and 24 h. Parameters of cytotoxicity were assayed by measuring LDH (lactate dehydrogenase) leakage into the medium. Peroxide concentration was tested by flow cytometry by measuring the fluorescence intensity of DCF (dichlorofluorescein). Gene expression of catalase was detected by measuring the respective mRNA and proteins, as well as protein level of HSP70. The enzymatic activity of catalase was also determined. Heat pre-treatment significantly reduced CsA cytotoxicity as well as the level of peroxide generation. The protective effect of the previous heat treatment (corroborated by the irreversible catalase inhibitor 3-aminotriazole) against the CsA cytotoxicity was due to an increased expression and activity of catalase that was significantly reduced by the effect of CsA. We conclude that heat pre-treatment strongly protects against CsA injury, and the mechanism of this protection is by means of inducing not only the expression of HSP70 but also the expression and activity of catalase, the main enzyme system involved in H(2)O(2) elimination.

Pattern Analyses Reveal Separate Experience-Based Fear Memories in the Human Right Amygdala.

PubMed

Braem, Senne; De Houwer, Jan; Demanet, Jelle; Yuen, Kenneth S L; Kalisch, Raffael; Brass, Marcel

2017-08-23

Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is often assumed to be fundamentally different from learning fear via instructions. An open question is whether fear-related brain areas respond differently to experienced CS-US contingencies than to merely instructed CS-US contingencies. Here, we contrasted two experimental conditions where subjects were instructed to expect the same CS-US contingencies while only one condition was characterized by prior experience with the CS-US contingency. Using multivoxel pattern analysis of fMRI data, we found CS-related neural activation patterns in the right amygdala (but not in other fear-related regions) that dissociated between whether a CS-US contingency had been instructed and experienced versus merely instructed. A second experiment further corroborated this finding by showing a category-independent neural response to instructed and experienced, but not merely instructed, CS presentations in the human right amygdala. Together, these findings are in line with previous studies showing that verbal fear instructions have a strong impact on both brain and behavior. However, even in the face of fear instructions, the human right amygdala still shows a separable neural pattern response to experience-based fear contingencies. SIGNIFICANCE STATEMENT In our study, we addressed a fundamental problem of the science of human fear learning and memory, namely whether fear learning via experience in humans relies on a neural pathway that can be separated from fear learning via verbal information. Using two new procedures and recent advances in the analysis of brain imaging data, we localized purely experience-based fear processing and memory in the right amygdala, thereby making a direct link between human and animal research. Copyright © 2017 the authors 0270-6474/17/378116-15$15.00/0.

Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

PubMed Central

Li, Hong-Peng; Komuta, Yukari; Kimura-Kuroda, Junko; van Kuppevelt, Toin H.

2013-01-01

Abstract Dermatan sulfate (DS) is synthesized from chondroitin sulfate (CS) by epimerization of glucuronic acid of CS to yield iduronic acid. In the present study, the role of CS and DS was examined in mice that received transection of nigrostriatal dopaminergic pathway followed by injection of glycosaminoglycan degrading enzymes into the lesion site. Two weeks after injury, fibrotic and glial scars were formed around the lesion, and transected axons did not regenerate beyond the fibrotic scar. Injection of chondroitinase ABC (ChABC), which degrades both CS and DS, completely suppressed the fibrotic scar formation, reduced the glial scar, and promoted the regeneration of dopaminergic axons. Injection of the DS-degrading enzyme chondroitinase B (ChB) also yielded similar results. By contrast, injection of chondroitinase AC (ChAC), a CS-degrading enzyme, did not suppress the fibrotic and glial scar formation, but reduced CS immunoreactivity and promoted the axonal regeneration. Addition of transforming growth factor-β1 (TGF-β1) to a co-culture of meningeal fibroblasts and cerebral astrocytes induces a fibrotic scar-like cell cluster. The effect of TGF-β1 on cluster formation was suppressed by treatment with ChABC or ChB, but not by ChAC. TGF-β1-induced cell cluster repelled neurites of neonatal cerebellar neurons, but addition of ChABC or ChAC suppressed the inhibitory property of clusters on neurite outgrowth. The present study is the first to demonstrate that DS and CS play different functions after brain injury: DS is involved in the lesion scar formation, and CS inhibits axonal regeneration. PMID:23438307

Investigation of the unique degradation phenomenon observed in CsSrBr3: Eu 5% scintillator crystals

NASA Astrophysics Data System (ADS)

Gokhale, S. S.; Loyd, M.; Stand, L.; Lindsey, A.; Swider, S.; Zhuravleva, M.; Melcher, C. L.

2016-10-01

CsSrBr3: Eu 5% is a promising compound scintillator for radiation detection and imaging applications. Light output and energy resolution measured for a crystal of volume 5×5×5 mm3 were 55,000±2000 ph/MeV and 5.6% at 662 keV respectively which is a significant improvement over previous reports. The hygroscopicity of the compound and the tendency of the scintillator crystals to degrade when exposed to the atmosphere necessitate the proper encapsulation of the crystals. It was observed that unlike other hygroscopic scintillator crystals CsSrBr3 undergoes a unique degradation while encapsulated in mineral oil. The light output of the crystal decreases over time, but there is no visually observed physical degradation of the crystal. This degradation is a reversible process wherein a degraded crystal can be subjected to annealing in vacuum in order to restore its original performance.

Tailored balance exercises on people with multiple sclerosis: A pilot randomized, controlled study.

PubMed

Brichetto, Giampaolo; Piccardo, Elisa; Pedullà, Ludovico; Battaglia, Mario Alberto; Tacchino, Andrea

2015-07-01

Altered integration of signals from visual (VIS), somatosensory (PROP) and vestibular system (VEST) lead to balance control impairments affecting the daily living activities of patients with multiple sclerosis (PwMS). As a consequence, tailored interventions could be crucial in improving efficacy of balance rehabilitation treatments. The objective of this paper is to assess the efficacy of tailored rehabilitation treatments for balance disorders based on visual, somatosensory and vestibular deficits versus traditional rehabilitation exercises. Thirty-two PwMS were assessed with the Berg Balance Scale (BBS), the composite score (CS) obtained by computerized dynamic posturography (CDP) test and the Modified Fatigue Impact Scale (MFIS). Based on CDP analysis, prevalent VIS, PROP or VEST deficits were identified and patients randomly allocated to a personalized (PRG) or traditional (TRG) rehabilitation group. BBS score showed a significant difference between pre- and post-treatment scores of 6.3 and 2.0 points respectively for PRG and TRG. CS showed a significant difference between pre- and post-treatment scores of 16.6 and 7.6 points respectively for PRG and TRG. No interaction effect was found for MFIS score. BBS and CS showed changes in the PRG group that met clinical relevant difference, underlining that tailored rehabilitation interventions based on patient-specific sensory system impairment could improve balance and postural control in PwMS. © The Author(s), 2015.

Visual Pathway Deficit in Female Fragile X Premutation Carriers: A Potential Endophenotype

ERIC Educational Resources Information Center

Keri, Szabolcs; Benedek, Gyorgy

2009-01-01

Previous studies indicated impaired magnocellular (M) and relatively spared parvocellular (P) visual pathway functioning in patients with fragile X syndrome. In this study, we assessed M and P pathways in 22 female fragile X premutation carriers with normal intelligence and in 20 healthy non-carrier controls. Testing procedure included visual…

The multiple sclerosis visual pathway cohort: understanding neurodegeneration in MS.

PubMed

Martínez-Lapiscina, Elena H; Fraga-Pumar, Elena; Gabilondo, Iñigo; Martínez-Heras, Eloy; Torres-Torres, Ruben; Ortiz-Pérez, Santiago; Llufriu, Sara; Tercero, Ana; Andorra, Magi; Roca, Marc Figueras; Lampert, Erika; Zubizarreta, Irati; Saiz, Albert; Sanchez-Dalmau, Bernardo; Villoslada, Pablo

2014-12-15

Multiple Sclerosis (MS) is an immune-mediated disease of the Central Nervous System with two major underlying etiopathogenic processes: inflammation and neurodegeneration. The latter determines the prognosis of this disease. MS is the main cause of non-traumatic disability in middle-aged populations. The MS-VisualPath Cohort was set up to study the neurodegenerative component of MS using advanced imaging techniques by focusing on analysis of the visual pathway in a middle-aged MS population in Barcelona, Spain. We started the recruitment of patients in the early phase of MS in 2010 and it remains permanently open. All patients undergo a complete neurological and ophthalmological examination including measurements of physical and disability (Expanded Disability Status Scale; Multiple Sclerosis Functional Composite and neuropsychological tests), disease activity (relapses) and visual function testing (visual acuity, color vision and visual field). The MS-VisualPath protocol also assesses the presence of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), general quality of life (SF-36) and visual quality of life (25-Item National Eye Institute Visual Function Questionnaire with the 10-Item Neuro-Ophthalmic Supplement). In addition, the imaging protocol includes both retinal (Optical Coherence Tomography and Wide-Field Fundus Imaging) and brain imaging (Magnetic Resonance Imaging). Finally, multifocal Visual Evoked Potentials are used to perform neurophysiological assessment of the visual pathway. The analysis of the visual pathway with advance imaging and electrophysilogical tools in parallel with clinical information will provide significant and new knowledge regarding neurodegeneration in MS and provide new clinical and imaging biomarkers to help monitor disease progression in these patients.

Evaluation of the efficacy and safety of a CS20® protective barrier gel containing OGT compared with topical aciclovir and placebo on functional and objective symptoms of labial herpes recurrences: a randomized clinical trial.

PubMed

Khemis, A; Duteil, L; Coudert, A C; Tillet, Y; Dereure, O; Ortonne, J P

2012-10-01

Topical or systemic antiviral drugs reduce the duration of herpes simplex virus 1 (HSV-1) recurrences but may not alleviate functional symptoms. To assess the efficacy and safety of CS20 (Acura 24(®) ) protective barrier gel versus topical aciclovir and placebo in resolving functional symptoms in HSV-1 labial recurrences. A prospective, randomized, single-centre, assessor-blinded study of CS20 versus topical aciclovir or placebo. The primary endpoint was the total score of four herpes-related functional symptoms (pain, burning, itching, and tingling sensations), evaluated by visual analogue scale (VAS). Secondary endpoints encompassed objective skin changes (oedema, crusting and erythema), evaluated by specific clinical scores. In a study of 106 patients, compared with placebo, a significant improvement in total functional symptom score was observed after 1 day of treatment in the CS20 group, but only after 7 days of treatment in the topical aciclovir group. Burning sensations were significantly reduced by CS20 compared with aciclovir (Days 1-2) or placebo (Days 1-7). Compared to placebo, CS20 significantly reduced pain intensity on Days 1-6. CS20 induced significant and early improvements in the clinical scores for oedema and crusting compared with placebo. Time to cure was similar for CS20 and aciclovir. The treatments were well tolerated and adverse events were comparable in the three treatment groups. Limitations  The single-centre and single-blind design of the study and the preselection of patients. CS20 showed superior effectiveness against functional symptoms (pain and burning) associated with HSV-1 labial recurrences and was similar to aciclovir for time to cure. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Interleukin-13-induced MUC5AC expression is regulated by a PI3K–NFAT3 pathway in mouse tracheal epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Fugui; Li, Wen; Zhou, Hongbin

Highlights: • IL-13 specifically induced NFAT3 activation in mouse tracheal epithelial cells. • CsA and LY294002 significantly blocked IL-13-induced MUC5AC production. • The PI3K–NFAT3 pathway is positively involved in IL-13-induced MUC5AC production. - Abstract: Interleukin-13 (IL-13) plays a critical role in asthma mucus overproduction, while the mechanisms underlying this process are not fully elucidated. Previous studies showed that nuclear factor of activated T cells (NFAT) is involved in the pathogenesis of asthma, but whether it can directly regulate IL-13-induced mucus (particularly MUC5AC) production is still not clear. Here we showed that IL-13 specifically induced NFAT3 activation through promoting its dephosphorylationmore » in air–liquid interface (ALI) cultures of mouse tracheal epithelial cells (mTECs). Furthermore, both Cyclosporin A (CsA, a specific NFAT inhibitor) and LY294002 (a Phosphoinositide 3-kinase (PI3K) inhibitor) significantly blocked IL-13-induced MUC5AC mRNA and protein production through the inhibition of NFAT3 activity. We also confirmed that CsA could not influence the forkhead Box A2 (Foxa2) and mouse calcium dependent chloride channel 3 (mClca3) expression in IL-13-induced MUC5AC production, which both are known to be important in IL-13-stimulated mucus expression. Our study is the first to demonstrate that the PI3K–NFAT3 pathway is positively involved in IL-13-induced mucus production, and provided novel insights into the molecular mechanism of asthma mucus hypersecretion.« less

HANABA TARANU regulates the shoot apical meristem and leaf development in cucumber (Cucumis sativus L.)

PubMed Central

Ding, Lian; Yan, Shuangshuang; Jiang, Li; Liu, Meiling; Zhang, Juan; Zhao, Jianyu; Zhao, Wensheng; Han, Ying-yan; Wang, Qian; Zhang, Xiaolan

2015-01-01

The shoot apical meristem (SAM) is essential for continuous organogenesis in higher plants, while the leaf is the primary source organ and the leaf shape directly affects the efficiency of photosynthesis. HANABA TARANU (HAN) encodes a GATA3-type transcription factor that functions in floral organ development, SAM organization, and embryo development in Arabidopsis, but is involved in suppressing bract outgrowth and promoting branching in grass species. Here the function of the HAN homologue CsHAN1 was characterized in cucumber, an important vegetable with great agricultural and economic value. CsHAN1 is predominantly expressed at the junction of the SAM and the stem, and can partially rescue the han-2 floral organ phenotype in Arabidopsis. Overexpression and RNAi of CsHAN1 transgenic cucumber resulted in retarded growth early after embryogenesis and produced highly lobed leaves. Further, it was found that CsHAN1 may regulate SAM development through regulating the WUSCHEL (WUS) and SHOOT MERISTEMLESS (STM) pathways, and mediate leaf development through a complicated gene regulatory network in cucumber. PMID:26320238

An evaluation of soil sampling for 137Cs using various field-sampling volumes.

PubMed

Nyhan, J W; White, G C; Schofield, T G; Trujillo, G

1983-05-01

The sediments from a liquid effluent receiving area at the Los Alamos National Laboratory and soils from an intensive study area in the fallout pathway of Trinity were sampled for 137Cs using 25-, 500-, 2500- and 12,500-cm3 field sampling volumes. A highly replicated sampling program was used to determine mean concentrations and inventories of 137Cs at each site, as well as estimates of spatial, aliquoting, and counting variance components of the radionuclide data. The sampling methods were also analyzed as a function of soil size fractions collected in each field sampling volume and of the total cost of the program for a given variation in the radionuclide survey results. Coefficients of variation (CV) of 137Cs inventory estimates ranged from 0.063 to 0.14 for Mortandad Canyon sediments, whereas CV values for Trinity soils were observed from 0.38 to 0.57. Spatial variance components of 137Cs concentration data were usually found to be larger than either the aliquoting or counting variance estimates and were inversely related to field sampling volume at the Trinity intensive site. Subsequent optimization studies of the sampling schemes demonstrated that each aliquot should be counted once, and that only 2-4 aliquots out of as many as 30 collected need be assayed for 137Cs. The optimization studies showed that as sample costs increased to 45 man-hours of labor per sample, the variance of the mean 137Cs concentration decreased dramatically, but decreased very little with additional labor.

Selective Antiprotozoal Activity of Nitric Oxide-releasing Chitosan Nanoparticles Against Trypanosoma cruzi: Toxicity and Mechanisms of Action.

PubMed

Contreras Lancheros, Cesar Armando; Pelegrino, Milena Trevisan; Kian, Danielle; Tavares, Eliandro Reis; Hiraiwa, Priscila Mazzochi; Goldenberg, Samuel; Nakamura, Celso Vataru; Yamauchi, Lucy Megumi; Pinge-Filho, Phileno; Seabra, Amedea Barozzi; Yamada-Ogatta, Sueli Fumie

2018-01-01

Chagas' disease, caused by Trypanosoma cruzi, was described for the first time over a hundred years ago. Nonetheless, clinically available drugs still lack effective and selective properties. Nitric oxide (NO) produced by activated macrophages controls the progression of disease by killing the parasite. Here, chitosan nanoparticles (CS NPs) were synthesized and mercaptosuccinic acid (MSA), the NO donor precursor, was encapsulated into CS NPs, forming MSA-CS NPs, which had hydrodynamic size of 101.0±2.535 nm. Encapsulated MSA was nitrosated forming NO donor S-nitrosomercaptosuccinic acid-containing nanoparticles (S-nitroso-MSA-CS NPs). Kinetic data revealed a sustained release of NO from the nanoparticles. S-nitroso-MSA-CS NPs inhibited epimastigote proliferation and trypomastigote viability of T. cruzi, with IC50=75.0±6.5 µg·mL-1 and EC50=25.0±5.0 µg·mL-1, respectively. Treatment of peritoneal macrophages with nanoparticles decreased the number of T. cruzi-infected cells and the average number of intracellular replicative amastigotes per infected cells. Besides, the results have showed a selective behaviour of S-nitroso-MSA-CS NPs to parasites. Morphological and biochemical changes induced by these NO-releasing nanoparticles, such as cell shrinkage, cell cycle arrest, mitochondrial membrane depolarization and phosphatidylserine exposure on cell surface indicate that epimastigotes death is associated to the apoptotic pathway. S-nitroso-MSA-CS NPs are promising nanocarriers for the treatment of Chagas's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Xeroderma pigmentosum complementation group G associated with Cockayne syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vermeulen, W.; Jaspers, N.G.J.; Bootsma, D.

1993-07-01

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are two rare inherited disorders with a clinical and cellular hypersensitivity to the UV component of the sunlight spectrum. Although the two traits are generally considered as clinically and genetically distinct entities, on the biochemical level a defect in the nucleotide excision-repair (NER) pathway is involved in both. Classical CS patients are primarily deficient in the preferential repair of DNA damage in actively transcribed genes, whereas in most XP patients the genetic defect affects both [open quotes]preferential[close quotes] and [open quotes]overall[close quotes] NER modalities. Here the authors report a genetic study of twomore » unrelated, severely affected patients with the clinical characteristics of CS but with a biochemical defect typical of XP. By complementation analysis, using somatic cell fusion and nuclear microinjection of cloned repair genes, they assign these two patients to XP complementation group G, which previously was not associated with CS. This observation extends the earlier identification of two patients with a rare combined XP/CS phenotype within XP complementation groups B and D, respectively. It indicates that some mutations in at least three of the seven genes known to be involved in XP also can result in a picture of partial or even full-blown CS. It is concluded that the syndromes XP and CS are biochemically closely related and may be part of a broader clinical disease spectrum. The authors suggest, as a possible molecular mechanism underlying this relation, that the XPGC repair gene has an additional vital function, as shown for some other NER genes. 33 refs., 5 tabs.« less

Long-term effects of neonatal hypoxia-ischemia on structural and physiological integrity of the eye and visual pathway by multimodal MRI.

PubMed

Chan, Kevin C; Kancherla, Swarupa; Fan, Shu-Juan; Wu, Ed X

2014-12-09

Neonatal hypoxia-ischemia is a major cause of brain damage in infants and may frequently present visual impairments. Although advancements in perinatal care have increased survival, the pathogenesis of hypoxic-ischemic injury and the long-term consequences to the visual system remain unclear. We hypothesized that neonatal hypoxia-ischemia can lead to chronic, MRI-detectable structural and physiological alterations in both the eye and the brain's visual pathways. Eight Sprague-Dawley rats underwent ligation of the left common carotid artery followed by hypoxia for 2 hours at postnatal day 7. One year later, T2-weighted MRI, gadolinium-enhanced MRI, chromium-enhanced MRI, manganese-enhanced MRI, and diffusion tensor MRI (DTI) of the visual system were evaluated and compared between opposite hemispheres using a 7-Tesla scanner. Within the eyeball, systemic gadolinium administration revealed aqueous-vitreous or blood-ocular barrier leakage only in the ipsilesional left eye despite comparable aqueous humor dynamics in the anterior chamber of both eyes. Binocular intravitreal chromium injection showed compromised retinal integrity in the ipsilesional eye. Despite total loss of the ipsilesional visual cortex, both retinocollicular and retinogeniculate pathways projected from the contralesional eye toward ipsilesional visual cortex possessed stronger anterograde manganese transport and less disrupted structural integrity in DTI compared with the opposite hemispheres. High-field, multimodal MRI demonstrated in vivo the long-term structural and physiological deficits in the eye and brain's visual pathways after unilateral neonatal hypoxic-ischemic injury. The remaining retinocollicular and retinogeniculate pathways appeared to be more vulnerable to anterograde degeneration from eye injury than retrograde, transsynaptic degeneration from visual cortex injury. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Long-Term Effects of Neonatal Hypoxia-Ischemia on Structural and Physiological Integrity of the Eye and Visual Pathway by Multimodal MRI

PubMed Central

Chan, Kevin C.; Kancherla, Swarupa; Fan, Shu-Juan; Wu, Ed X.

2015-01-01

Purpose. Neonatal hypoxia-ischemia is a major cause of brain damage in infants and may frequently present visual impairments. Although advancements in perinatal care have increased survival, the pathogenesis of hypoxic-ischemic injury and the long-term consequences to the visual system remain unclear. We hypothesized that neonatal hypoxia-ischemia can lead to chronic, MRI-detectable structural and physiological alterations in both the eye and the brain's visual pathways. Methods. Eight Sprague-Dawley rats underwent ligation of the left common carotid artery followed by hypoxia for 2 hours at postnatal day 7. One year later, T2-weighted MRI, gadolinium-enhanced MRI, chromium-enhanced MRI, manganese-enhanced MRI, and diffusion tensor MRI (DTI) of the visual system were evaluated and compared between opposite hemispheres using a 7-Tesla scanner. Results. Within the eyeball, systemic gadolinium administration revealed aqueous-vitreous or blood-ocular barrier leakage only in the ipsilesional left eye despite comparable aqueous humor dynamics in the anterior chamber of both eyes. Binocular intravitreal chromium injection showed compromised retinal integrity in the ipsilesional eye. Despite total loss of the ipsilesional visual cortex, both retinocollicular and retinogeniculate pathways projected from the contralesional eye toward ipsilesional visual cortex possessed stronger anterograde manganese transport and less disrupted structural integrity in DTI compared with the opposite hemispheres. Conclusions. High-field, multimodal MRI demonstrated in vivo the long-term structural and physiological deficits in the eye and brain's visual pathways after unilateral neonatal hypoxic-ischemic injury. The remaining retinocollicular and retinogeniculate pathways appeared to be more vulnerable to anterograde degeneration from eye injury than retrograde, transsynaptic degeneration from visual cortex injury. PMID:25491295

Pathogen exploitation of an abscisic acid- and jasmonate-inducible MAPK phosphatase and its interception by Arabidopsis immunity.

PubMed

Mine, Akira; Berens, Matthias L; Nobori, Tatsuya; Anver, Shajahan; Fukumoto, Kaori; Winkelmüller, Thomas M; Takeda, Atsushi; Becker, Dieter; Tsuda, Kenichi

2017-07-11

Phytopathogens promote virulence by, for example, exploiting signaling pathways mediated by phytohormones such as abscisic acid (ABA) and jasmonate (JA). Some plants can counteract pathogen virulence by invoking a potent form of immunity called effector-triggered immunity (ETI). Here, we report that ABA and JA mediate inactivation of the immune-associated MAP kinases (MAPKs), MPK3 and MPK6, in Arabidopsis thaliana ABA induced expression of genes encoding the protein phosphatases 2C (PP2Cs), HAI1 , HAI2 , and HAI3 through ABF/AREB transcription factors. These three HAI PP2Cs interacted with MPK3 and MPK6 and were required for ABA-mediated MPK3/MPK6 inactivation and immune suppression. The bacterial pathogen Pseudomonas syringae pv. tomato ( Pto ) DC3000 activates ABA signaling and produces a JA-mimicking phytotoxin, coronatine (COR), that promotes virulence. We found that Pto DC3000 induces HAI1 through COR-mediated activation of MYC2, a master transcription factor in JA signaling. HAI1 dephosphorylated MPK3 and MPK6 in vitro and was necessary for COR-mediated suppression of MPK3/MPK6 activation and immunity. Intriguingly, upon ETI activation, A. thaliana plants overcame the HAI1-dependent virulence of COR by blocking JA signaling. Finally, we showed conservation of induction of HAI PP2Cs by ABA and JA in other Brassicaceae species. Taken together, these results suggest that ABA and JA signaling pathways, which are hijacked by the bacterial pathogen, converge on the HAI PP2Cs that suppress activation of the immune-associated MAPKs. Also, our data unveil interception of JA-signaling activation as a host counterstrategy against the bacterial suppression of MAPKs during ETI.

Transcriptomic Analysis Implies That GA Regulates Sex Expression via Ethylene-Dependent and Ethylene-Independent Pathways in Cucumber (Cucumis sativus L.).

PubMed

Zhang, Yan; Zhao, Guiye; Li, Yushun; Mo, Ning; Zhang, Jie; Liang, Yan

2017-01-01

Sex differentiation of flower buds is an important developmental process that directly affects fruit yield of cucumber ( Cucumis sativus L.). Plant hormones, such as gibberellins (GAs) and ethylene can promote development of male and female flowers, respectively, however, the regulatory mechanisms of GA-induced male flower formation and potential involvement of ethylene in this process still remain unknown. In this study, to unravel the genes and gene networks involved in GA-regulated cucumber sexual development, we performed high throughout RNA-Seq analyses that compared the transcriptomes of shoot tips between GA 3 treated and untreated gynoecious cucumber plants. Results showed that GA 3 application markedly induced male flowers but decreased ethylene production in shoot tips. Furthermore, the transcript levels of M ( CsACS2 ) gene, ethylene receptor CsETR1 and some ethylene-responsive transcription factors were dramatically changed after GA 3 treatment, suggesting a potential involvement of ethylene in GA-regulated sex expression of cucumber. Interestingly, GA 3 down-regulated transcript of a C-class floral homeotic gene, CAG2 , indicating that GA may also influence cucumber sex determination through an ethylene-independent process. These results suggest a novel model for hormone-mediated sex differentiation and provide a theoretical basis for further dissection of the regulatory mechanism of male flower formation in cucumber. Statement: We reveal that GA can regulate sex expression of cucumber via an ethylene-dependent manner, and the M ( CsACS2 ), CsETR1 , and ERFs are probably involved in this process. Moreover, CAG2 , a C-class floral homeotic gene, may also participate in GA-modulated cucumber sex determination, but this pathway is ethylene-independent.

Clonorchis sinensis acetoacetyl-CoA thiolase: identification and characterization of its potential role in surviving in the bile duct.

PubMed

Lin, Jinsi; Qu, Hongling; Chen, Guishan; He, Lei; Xu, Yanquan; Xie, Zhizhi; Ren, Mengyu; Sun, Jiufeng; Li, Shan; Chen, Wenjun; Chen, Xueqing; Wang, Xiaoyun; Li, Xuerong; Liang, Chi; Huang, Yan; Yu, Xinbing

2015-02-25

Clonorchis sinensis (C. sinensis) inhabits in bile duct of the host. However, the mechanisms involved in why C. sinensis can survive in the bile environment containing lipids have not yet been explored. In this study, C. sinensis acetoacetyl-CoA thiolase (CsACAT), a member of the thiolase family which has a key role in the beta oxidation pathway of fatty acid production, was identified and characterized to understand its potential role in adapting to the bile environment. The encoding sequence, conserved domains and spatial structure of CsACAT were identified and analyzed by bioinformatic tools. Recombinant CsACAT (rCsACAT) was obtained using a procaryotic expression system. The expression pattern of CsACAT was confirmed by quantitative real-time PCR, western blotting, and immunofluorescence. Gradients of lecithin were then set to culture C. sinensis adults in vitro and the survival rate of C. sinensis was analyzed, as well as the expression level and enzymatic activity of CsACAT in different lipid environments. Hypercholesteremia rabbit models were established by feeding with a hyperlipidemic diet and then infected intragastrically with C. sinensis. One and a half months later, the worm burdens and the expression level of CsACAT was detected. CsACAT was confirmed to be a member of the thiolase family and present in the excretory/secretory proteins of C. sinensis. CsACAT was specifically localized at the vitellarium and sub-tegumental muscle layer in adult worms. The mRNA level of CsACAT in eggs was higher than those in adult worms and metacercariae. When adult worms were cultured with higher concentration of lecithin, the expression level and enzyme activity of CsACAT were up-regulated. The survival rate of adult worms was higher than control group. More adult worms were recovered from hypercholesteremia rabbit models. The expression level of CsACAT in these worms was higher than control group. Our results implied that C. sinensis might sense lipid levels and survive better in the bile environment with higher lipid levels. C. sinensis might modulate the expression and enzymatic activity of CsACAT, an enzyme involved in fatty acid metabolism, for energy or physical requirements to adapt to the host.

Radiation doses for Marshall Islands Atolls affected by U.S. nuclear testing: all exposure pathways, remedial measures, and environmental loss of (137)Cs.

PubMed

Robison, William L; Hamilton, Terry F

2010-01-01

Radiation doses calculated for people resettling Bikini Island at Bikini Atoll, Enjebi Island at Enewetak Atoll, Rongelap Island at Rongelap Atoll, and Utrōk Island at Utrōk Atoll are presented. Residence is assumed to begin in 2010. In previous dose assessments it was shown that (137)Cs accounts for about 98% of the total dose for returning residents. About 85 to 90% (depending on the atoll) is via consumption of locally grown foods containing (137)Cs, and about 10 to 15% is due to external exposure from (137)Cs in the soil. These assessments were made using only the radiological half-life of (137)Cs (30.1 y). We have shown since that there is an environmental loss of (137)Cs from soil to groundwater that results in a more rapid loss of (137)Cs from the atoll ecosystem. The mean effective half-life of (137)Cs at the atolls is 8.5 y. Moreover, treatment of coconut trees with potassium (K) reduces (137)Cs concentration in drinking coconut meat at Bikini Atoll to about 5% of pretreatment concentrations. The magnitude of reduction is dependent on the concentration of (137)Cs in soil, and thereby in food crops, and is less for Enjebi and Rongelap Islands than for Bikini Island. Treatment of food crops and fruit trees with K and removal of the top 15 cm of soil around houses and community buildings prior to construction to reduce external exposure where people spend most of their time has been presented to the communities as a "Combined Option" remediation strategy. Doses presented here are calculated using the Combined Option, effective half-life of (137)Cs at the atolls, and a diet of both imported and local foods. The average natural background dose in the Marshall Islands, plus the anthropogenic nuclear test-related dose at Bikini, Enjebi, and Rongelap Islands, is less for each of the islands than the average background dose in the U.S. and Europe.

The dorsal "action" pathway.

PubMed

Gallivan, Jason P; Goodale, Melvyn A

2018-01-01

In 1992, Goodale and Milner proposed a division of labor in the visual pathways of the primate cerebral cortex. According to their account, the ventral pathway, which projects to occipitotemporal cortex, constructs our visual percepts, while the dorsal pathway, which projects to posterior parietal cortex, mediates the visual control of action. Although the framing of the two-visual-system hypothesis has not been without controversy, it is clear that vision for action and vision for perception have distinct computational requirements, and significant support for the proposed neuroanatomic division has continued to emerge over the last two decades from human neuropsychology, neuroimaging, behavioral psychophysics, and monkey neurophysiology. In this chapter, we review much of this evidence, with a particular focus on recent findings from human neuroimaging and monkey neurophysiology, demonstrating a specialized role for parietal cortex in visually guided behavior. But even though the available evidence suggests that dedicated circuits mediate action and perception, in order to produce adaptive goal-directed behavior there must be a close coupling and seamless integration of information processing across these two systems. We discuss such ventral-dorsal-stream interactions and argue that the two pathways play different, yet complementary, roles in the production of skilled behavior. Copyright © 2018 Elsevier B.V. All rights reserved.

Down-regulation of ATF2 in the inhibition of T-2-toxin-induced chondrocyte apoptosis by selenium chondroitin sulfate nanoparticles

NASA Astrophysics Data System (ADS)

Han, Jing; Guo, Xiong

2013-12-01

Selenium chondroitin sulfate nanoparticles (SeCS) with a size range of 30-200 nm were obtained in our previous study. Meanwhile, the up-regulated expression of ATF2 mRNA and protein levels could be observed in the cartilage from Kashin-Beck disease (KBD) patients. In this paper, we investigated the inhibition effect of SeCS on T-2-toxin-induced apoptosis of chondrocyte from KBD patients. Here, we found that when the chondrocytes were treated with T-2 toxin, the chondrocyte apoptosis performed in a concentration-dependent manner. The apoptosis of chondrocyte induced by T-2 toxin involved the increased levels of ATF2, JNK and p38 mRNAs and related protein expression. SeCS could partly block the T-2-toxin-induced chondrocyte apoptosis by decreasing the expression of ATF2, JNK and p38 mRNAs and p-JNK, p-38, ATF2 and p-ATF2 proteins. JNK and p38 pathways involved in the apoptosis of chondrocyte induced by T-2 toxin, and SeCS was efficient in the inhibition of chondrocyte apoptosis by T-2 toxin. These results suggested that SeCS had a potential for further prevention and treatment for KBD as well as other selenium deficiency disease.

Molecular mechanisms of immunosuppression by cyclosporins.

PubMed

Zenke, G; Baumann, G; Wenger, R; Hiestand, P; Quesniaux, V; Andersen, E; Schreier, M H

1993-06-23

Despite the successful clinical application of the immunosuppressive drug cyclosporin A (CsA, Sandimmun), its precise mechanism of action in the process of T cell activation remains elusive. CsA binds to the high-affinity cytosolic receptor cyclophilin whose peptidyl-prolyl cis-trans isomerase activity is inhibited upon binding. The linkage of this effect with the inhibition of the T cell receptor-mediated signal transduction pathway, which leads to a suppression of lymphokine gene transcription, is still unclear. We analyzed the relationship between cyclophilin-binding and immunosuppressive activity (e.g., effect on IL-2 transcription) of cyclosporin derivatives in vitro. The results show that binding to cyclophilin is required, but not sufficient for immunosuppression. Cyclosporin analogues which completely lack immunosuppressive activity but fully retained their cyclophilin-binding capacity antagonize the immunosuppressive activity of CsA. These derivatives inhibit the isomerase activity of cyclophilin, which clearly demonstrates that inhibition of the cyclophilin isomerase activity does not lead to immunosuppression. In analogy to the other immunosuppressants of microbial origin, FK-506 and rapamycin, a specific structure of the "effector" domain of CsA, which is unrelated to the cyclophilin-binding domain, determines the biological activity. In the nucleus, CsA interferes with the DNA-binding of inducible transcription factors to their respective DNA motifs within lymphokine promoters by affecting intracellular translocation of transcription factor subunits.

Contrast Sensitivity for Motion Detection and Direction Discrimination in Adolescents with Autism Spectrum Disorders and Their Siblings

ERIC Educational Resources Information Center

Koh, Hwan Cui; Milne, Elizabeth; Dobkins, Karen

2010-01-01

The magnocellular (M) pathway hypothesis proposes that impaired visual motion perception observed in individuals with Autism Spectrum Disorders (ASD) might be mediated by atypical functioning of the subcortical M pathway, as this pathway provides the bulk of visual input to cortical motion detectors. To test this hypothesis, we measured luminance…

Distribution of oceanic 137Cs from the Fukushima Dai-ichi Nuclear Power Plant simulated numerically by a regional ocean model.

PubMed

Tsumune, Daisuke; Tsubono, Takaki; Aoyama, Michio; Hirose, Katsumi

2012-09-01

Radioactive materials were released to the environment from the Fukushima Dai-ichi Nuclear Power Plant as a result of the reactor accident after the Tohoku earthquake and tsunami of 11 March 2011. The measured (137)Cs concentration in a seawater sample near the Fukushima Dai-ichi Nuclear Power Plant site reached 68 kBq L(-1) (6.8 × 10(4)Bq L(-1)) on 6 April. The two major likely pathways from the accident site to the ocean existed: direct release of high radioactive liquid wastes to the ocean and the deposition of airborne radioactivity to the ocean surface. By analysis of the (131)I/(137)Cs activity ratio, we determined that direct release from the site contributed more to the measured (137)Cs concentration than atmospheric deposition did. We then used a regional ocean model to simulate the (137)Cs concentrations resulting from the direct release to the ocean off Fukushima and found that from March 26 to the end of May the total amount of (137)Cs directly released was 3.5 ± 0.7 PBq ((3.5 ± 0.7) × 10(15)Bq). The simulated temporal change in (137)Cs concentrations near the Fukushima Daini Nuclear Power Plant site agreed well with observations. Our simulation results showed that (1) the released (137)Cs advected southward along the coast during the simulation period; (2) the eastward-flowing Kuroshio and its extension transported (137)C during May 2011; and (3) (137)Cs concentrations decreased to less than 10 BqL(-1) by the end of May 2011 in the whole simulation domain as a result of oceanic advection and diffusion. We compared the total amount and concentration of (137)Cs released from the Fukushima Dai-ichi reactors to the ocean with the (137)Cs released to the ocean by global fallout. Even though the measured (137)Cs concentration from the Fukushima accident was the highest recorded, the total released amount of (137)Cs was not very large. Therefore, the effect of (137)Cs released from the Fukushima Dai-ichi reactors on concentration in the whole North Pacific was smaller than that of past release events such as global fallout, and the amount of (137)Cs expected to reach other oceanic basins is negligible comparing with the past radioactive input. Copyright © 2011 Elsevier Ltd. All rights reserved.

Grooved Glaucoma Drainage Devices That Continuously Deliver Cyclosporine A Decrease Postsurgical Scar Formation in Rabbit Eyes.

PubMed

Dai, Zhaoxing; Yu, Xiaobo; Sun, Jianguo; Sun, Xinghuai

2017-03-01

To study the functional outcomes of filtration surgery by implanting improved glaucoma drainage devices (GDDs) comprising surface grooves and a composite coating of cyclosporine A (CsA) and PLGA in experimental rabbit eyes. Improved GDDs were designed and prepared by modifying normal GDD with surface grooves and a CsA-PLGA composite coating. Normal GDDs, grooved GDDs (G-GDDs), and G-GDDs with a CsA-PLGA composite coating (CsA@G-GDD) were implanted into 18 rabbit eyes (six eyes per group). The intraocular pressure (IOP), bleb survival time, bleb morphology, and anterior chamber reactions were assessed for up to 12 weeks after GDD implantation. The IOPs were compared statistically among the three groups. Bleb morphology was quantified using the Indiana Bleb Appearance Grading Scale. Anterior chamber radiography was performed to check whether the filtrating pathway was blocked, and determine the drainage time and diffusion area of the contrast agent. Hematoxylin and eosin staining and immunohistochemistry were conducted to assess how the GDDs slowed or prevented scar formation. The improved GDDs were successfully prepared and implanted in 18 rabbit eyes without severe surgical complications. Bleb survival time was significantly longer and IOP was significantly lower in the G-GDD and CsA@G-GDD groups compared with the GDD group (all, P < 0.001). Blebs were significantly higher in the CsA@G-GDD group than in the GDD and G-GDD groups (P = 0.003). Anterior chamber radiography revealed more unobstructed filtration channels in the CsA@G-GDD group than in the GDD group (P = 0.032). Postsurgical scar formation was less extensive in the G-GDD and CsA@G-GDD groups than in the GDD group. Compared with the normal GDDs, G-GDDs with a CsA-PLGA coating inhibited postsurgical scar formation and improved the surgical success rate, and might represent an alternative to existing glaucoma filtration devices.

Identification, immunolocalization, and immunological characterization of nitric oxide synthase-interacting protein from Clonorchis sinensis.

PubMed

Bian, Meng; Li, Shan; Wang, Xiaoyun; Xu, Yanquan; Chen, Wenjun; Zhou, Chenhui; Chen, Xueqing; He, Lei; Xu, Jin; Liang, Chi; Wu, Zhongdao; Huang, Yan; Li, Xuerong; Yu, Xinbing

2014-05-01

Recently, accumulating evidences indicate that nitric oxide (NO) is a potent mediator with diverse roles in regulating cellular functions, signaling pathways, and variety of pathological processes. In the present study, using data from the published genomic for Clonorchis sinensis (C. sinensis), we investigated a gene encoding nitric oxide synthase-interacting protein (NOSIP) of C. sinensis. Recombinant CsNOSIP (rCsNOSIP) was expressed and purified from Escherichia coli BL21. The open reading frame of CsNOSIP comprises 867 bp which encodes 289 amino acids and shares 72.9, 45.2, 47, 46.4, and 45.8% identity with NOSIP from Schistosoma mansoni, Xenopus laevis, Rattus norvegicus, Mus musculus, and Homo sapiens, respectively. Bioinformatics analysis suggested that the full-length sequence contains an eNOS-interacting domain and numerous B-cell epitopes. Quantitative RT-PCR indicated that CsNOSIP differentially transcribed throughout the adult worms, metacercariae, and egg stages of C. sinensis, and were highly expressed in the adult worms. Moreover, western blot analysis showed that the rCsNOSIP could be detected by the serum from BALB/c mice infected with C. sinensis and the serum from BALB/c mice immunized with excretory/secretory products (ESPs). Furthermore, immunolocalization assay showed that CsNOSIP was specifically localized in the intestine, vitellarium, and eggs of adult worm. Both immunoblot and immunolocalization results demonstrated that CsNOSIP was one component of ESPs of C. sinensis, which could be supported by SignalP analysis. Moreover, analysis of the antibody subclass and cytokine profile demonstrated that subcutaneously immunized BALB/c mice with rCsNOSIP could significantly enhance serum IgG1 level and up-regulate expression of IL-4 and IL-6 in the splenocytes. Our results suggested that CsNOSIP was an important antigen exposed to host immune system and probably involved in immune regulation of host by inducing Th2-polarized immune response.

Genome-wide characterization and expression analysis of citrus NUCLEAR FACTOR-Y (NF-Y) transcription factors identified a novel NF-YA gene involved in drought-stress response and tolerance.

PubMed

Pereira, Suzam L S; Martins, Cristina P S; Sousa, Aurizangela O; Camillo, Luciana R; Araújo, Caroline P; Alcantara, Grazielle M; Camargo, Danielle S; Cidade, Luciana C; de Almeida, Alex-Alan F; Costa, Marcio G C

2018-01-01

Nuclear factor Y (NF-Y) is a ubiquitous transcription factor found in eukaryotes. It is composed of three distinct subunits called NF-YA, NF-YB and NF-YC. NF-Ys have been identified as key regulators of multiple pathways in the control of development and tolerance to biotic and abiotic factors. The present study aimed to identify and characterize the complete repertoire of genes coding for NF-Y in citrus, as well as to perform the functional characterization of one of its members, namely CsNFYA5, in transgenic tobacco plants. A total of 22 genes coding for NF-Y were identified in the genomes of sweet orange (Citrus sinensis) and Clementine mandarin (C. clementina), including six CsNF-YAs, 11 CsNF-YBs and five CsNF-YCs. Phylogenetic analyses showed that there is a NF-Y orthologous in the Clementine genome for each sweet orange NF-Y gene; this was not observed when compared to Arabidopsis thaliana. CsNF-Y proteins shared the same conserved domains with their orthologous proteins in other organisms, including mouse. Analysis of gene expression by RNA-seq and EST data demonstrated that CsNF-Ys have a tissue-specific and stress inducible expression profile. qRT-PCR analysis revealed that CsNF-YA5 exhibits differential expression in response to water deficit in leaves and roots of citrus plants. Overexpression of CsNF-YA5 in transgenic tobacco plants contributed to the reduction of H2O2 production under dehydration conditions and increased plant growth and photosynthetic rate under normal conditions and drought stress. These biochemical and physiological responses to drought stress promoted by CsNF-YA5 may confer a productivity advantage in environments with frequent short-term soil water deficit.

VISIBIOweb: visualization and layout services for BioPAX pathway models

PubMed Central

Dilek, Alptug; Belviranli, Mehmet E.; Dogrusoz, Ugur

2010-01-01

With recent advancements in techniques for cellular data acquisition, information on cellular processes has been increasing at a dramatic rate. Visualization is critical to analyzing and interpreting complex information; representing cellular processes or pathways is no exception. VISIBIOweb is a free, open-source, web-based pathway visualization and layout service for pathway models in BioPAX format. With VISIBIOweb, one can obtain well-laid-out views of pathway models using the standard notation of the Systems Biology Graphical Notation (SBGN), and can embed such views within one's web pages as desired. Pathway views may be navigated using zoom and scroll tools; pathway object properties, including any external database references available in the data, may be inspected interactively. The automatic layout component of VISIBIOweb may also be accessed programmatically from other tools using Hypertext Transfer Protocol (HTTP). The web site is free and open to all users and there is no login requirement. It is available at: http://visibioweb.patika.org. PMID:20460470

Inhibition of TGF-β1/Smad signal pathway is involved in the effect of Cordyceps sinensis against renal fibrosis in 5/6 nephrectomy rats.

PubMed

Pan, Ming-Ming; Zhang, Ming-Hui; Ni, Hai-Feng; Chen, Jun-Feng; Xu, Min; Phillips, Aled Owain; Liu, Bi-Cheng

2013-08-01

The present study aimed to investigate the effects of Cordyceps sinensis on renal fibrosis and its possible mechanisms. Sprague-Dawley rats were randomly divided into three groups: sham operation (SHAM) group, 5/6 subtotal nephrectomy (SNx) untreated group, and 5/6 subtotal nephrectomy treated with C. sinensis (2.0 g/kg d) (CS) group. Rats were studied 12 weeks after the surgery, and the CS group presented with significantly lower proteinuria, and better renal function compared with the SNx group (p<0.05). Pathological study showed that the glomerulosclerosis tubulointerstitial injury score was significantly reduced in the CS group compared with the SNx group. Furthermore, the mRNA expression of TGF-β1, Smad2 and Smad3 and the protein expression of TGF-β1, TβRI, TβRII and p-Smad2/3 were attenuated by the C. sinensis treatment. In constrast, the mRNA and protein expression of Smad7 was upregulated. Furthermore, the expression of α-SMA and FSP1 was also significantly attenuated, accompanied by the increasing expression of E-cadherin, suggesting the inhibition of the epithelial-mesenchymal transition (EMT). C. sinensis exerted its antifibrotic effect on the SNx rats through the inhibition of the TGF-β1/Smad pathway. Copyright © 2013. Published by Elsevier Ltd.

Clonorchis sinensis granulin: identification, immunolocalization, and function in promoting the metastasis of cholangiocarcinoma and hepatocellular carcinoma.

PubMed

Wang, Caiqin; Lei, Huali; Tian, Yanli; Shang, Mei; Wu, Yinjuan; Li, Ye; Zhao, Lu; Shi, Mengchen; Tang, Xin; Chen, Tingjin; Lv, Zhiyue; Huang, Yan; Tang, Xiaoping; Yu, Xinbing; Li, Xuerong

2017-05-25

Long-term infections by Clonorchis sinensis are associated with cholangitis, cholecystitis, liver fibrosis, cirrhosis, and even liver cancer. Molecules from the worm play vital roles in disease progress. In the present study, we identified and explored molecular characterization of C. sinensis granulin (CsGRN), a growth factor-like protein from C. sinensis excretory/secretory products (CsESPs). The encoding sequence and conserved domains of CsGRN were identified and analysed by bioinformatics tools. Recombinant CsGRN (rCsGRN) protein was expressed in Escherichia coli BL21 (DE3). The localisation of CsGRN in adult worms and Balb/c mice infected with C. sinensis was investigated by immunofluorescence and immunohistochemistry, respectively. Stable CsGRN-overexpressed cell lines of hepatoma cells (PLC-GRN cells) and cholangiocarcinoma cells (RBE-GRN cells) were constructed by transfection of eukaryotic expression plasmid of pEGFP-C1-CsGRN. The effects on cell migration and invasion of CsGRN were assessed through the wound-healing assay and transwell assay. The levels of matrix metalloproteinase 2 and 9 (MMP2 and MMP9) in PLC-GRN or RBE-GRN cells were detected by real-time PCR (qRT-PCR). The levels of E-cadherin, vimentin, N-cadherin, zona occludens proteins (ZO-1), β-catenin, phosphorylated ERK (p-ERK) and phosphorylated AKT (p-AKT) were analysed by Western blotting. CsGRN, including the conserved GRN domains, was confirmed to be a member of the granulin family. CsGRN was identified as an ingredient of CsESPs. CsGRN was localised in the tegument and testes of the adult worm. Furthermore, it appeared in the cytoplasm of hepatocytes and biliary epithelium cells from infected Balb/c mouse. The enhancement of cell migration and invasion of PLC-GRN and RBE-GRN cells were observed. In addition, CsGRN upregulated the levels of vimentin, N-cadherin, β-catenin, MMP2 and MMP9, while it downregulated the level of ZO-1 in PLC-GRN/RBE-GRN cells. In total proteins of liver tissue from rCsGRN immunised Balb/c mice, vimentin level decreased, while E-cadherin level increased when compared with the control groups. Meanwhile, the levels of p-ERK reached a peak at 4 weeks post immunisation and the level of p-AKT did at 2 weeks after immunisation. The encoding sequence and molecular characteristics of CsGRN were identified. As a member of granulin superfamily, CsGRN induced mesenchymal characteristics of PLC and RBE cells and was found to regulate the activities of the downstream molecules of the ERK and PI3K/AKT signalling pathways, which could contribute to the enhancement of cell migration and invasion.

Beyond sensory images: Object-based representation in the human ventral pathway

PubMed Central

Pietrini, Pietro; Furey, Maura L.; Ricciardi, Emiliano; Gobbini, M. Ida; Wu, W.-H. Carolyn; Cohen, Leonardo; Guazzelli, Mario; Haxby, James V.

2004-01-01

We investigated whether the topographically organized, category-related patterns of neural response in the ventral visual pathway are a representation of sensory images or a more abstract representation of object form that is not dependent on sensory modality. We used functional MRI to measure patterns of response evoked during visual and tactile recognition of faces and manmade objects in sighted subjects and during tactile recognition in blind subjects. Results showed that visual and tactile recognition evoked category-related patterns of response in a ventral extrastriate visual area in the inferior temporal gyrus that were correlated across modality for manmade objects. Blind subjects also demonstrated category-related patterns of response in this “visual” area, and in more ventral cortical regions in the fusiform gyrus, indicating that these patterns are not due to visual imagery and, furthermore, that visual experience is not necessary for category-related representations to develop in these cortices. These results demonstrate that the representation of objects in the ventral visual pathway is not simply a representation of visual images but, rather, is a representation of more abstract features of object form. PMID:15064396

Visual circuits of the avian telencephalon: evolutionary implications

NASA Technical Reports Server (NTRS)

Shimizu, T.; Bowers, A. N.

1999-01-01

Birds and primates are vertebrates that possess the most advanced, efficient visual systems. Although lineages leading to these two classes were separated about 300 million years ago, there are striking similarities in their underlying neural mechanisms for visual processing. This paper discusses such similarities with special emphasis on the visual circuits in the avian telencephalon. These similarities include: (1) the existence of two parallel visual pathways and their distinct telencephalic targets, (2) anatomical and functional segregation within the visual pathways, (3) laminar organization of the telencephalic targets of the pathways (e.g. striate cortex in primates), and (4) possible interactions between multiple visual areas. Additional extensive analyses are necessary to determine whether these similarities are due to inheritance from a common ancestral stock or the consequences of convergent evolution based on adaptive response to similar selective pressures. Nevertheless, such a comparison is important to identify the general and specific principles of visual processing in amniotes (reptiles, birds, and mammals). Furthermore, these principles in turn will provide a critical foundation for understanding the evolution of the brain in amniotes.

Antibodies against Clonorchis sinensis LDH could cross-react with LDHB localizing on the plasma membrane of human hepatocarcinoma cell SMMC-7721 and induce apoptosis.

PubMed

Song, Tianzhang; Gan, Wenjia; Chen, Jintao; Huang, Lilin; Yin, Hongling; He, Tailong; Huang, Huaiqiu; Hu, Xuchu

2016-04-01

Lactate dehydrogenase (LDH) is a terminal enzyme in anaerobic glycolytic pathway. It widely exists in various organisms and is in charge of converting the glycolysis product pyruvic acid to lactic acid. Most parasites, including Clonorchis sinensis, predominantly depend on glycolysis to provide energy. Bioinformatic analysis predicts that the LDHs from many species have more than one transmembrane region, suggesting that it may be a membrane protein. C. sinensis LDH (CsLDH) has been confirmed as a transmembrane protein mainly located in the tegument. The antibodies against CsLDH can inhibit the worm's energy metabolism, kill the worm, and may have the same effects on human cancer cells. In this study, we cloned and characterized human LDHA (HsLDHA), HsLDHB, and CsLDH. Semi-quantitative real-time RCP showed that HsLDHB only existed in hepatocarcinoma cell SMMC-7721. Confocal microscopy and Western blot experiments revealed that HsLDHB was localized in the plasma membrane of SMMC-7721 cells, and the antibodies against CsLDH could cross-react with it. This cross-reaction could inhibit the enzymatic activity of HsLDHB. The cancer cells co-cultured with anti-CsLDH sera showed a significant decrease in cell proliferation rate and increases in caspase 9 and reactive oxygen species (ROS) levels. Therefore, anti-CsLDH antibodies can induce the apoptosis of cancer cells SMMC-7721 and may serve as a new tool to inhibit tumor.

SAXS characterization of the interactions among digested food compounds and the anti-oxidant and anti-inflammatory activities of the formed nanocomplexes.

PubMed

Yang, Yingkang; Wang, Xiaoqi; Chen, Guijie; Zhou, Wenhua; Zeng, Xiaoxiong; Hu, Bing; Li, Yunqi; Huang, Qingrong

2018-06-06

In the present study, small angle X-ray scattering (SAXS) is applied to investigate the interaction between caseinophosphopeptides (CPP), the major digested product of milk protein, and chitosan (CS) under simulated gastrointestinal (GI) pH conditions. The change in pH value from the gastric to small intestinal environment induces complexation between CPP and CS, which is mainly driven by electrostatic interactions. The fractal dimension (Df) value of the domains inside the CPP-CS complexes is greater than 3, indicating the formation of dense particles/aggregates at the nanoscale. The Df value generally increases with an increase in the CS/CPP mass ratio. As a representative of polyphenols, (-)-epigallocatechin gallate (EGCG) associates with CS and CPP, forming nanocomplexes with a spherical shape and average particle size of around 208 nm. The formed CS-EGCG-CPP nanocomplexes do not affect the antioxidant activity of EGCG in the in vitro assays. Moreover, in the cellular assay, the nanocomplexes protect the RAW264.7 cells against H2O2-induced oxidative injury. In addition, the nanocomplexes significantly inhibit the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), TNF-α, IL-1β and IL-6. Furthermore, they inhibit the expression of iNOS, phosphorylation and degradation of IκB, as well as the translocation of NF-κB p65; this indicates that the mechanism for their anti-inflammatory activity is via the mediation of the NF-κB signaling pathway.

Airway epithelial cell PPARγ modulates cigarette smoke-induced chemokine expression and emphysema susceptibility in mice.

PubMed

Solleti, Siva Kumar; Simon, Dawn M; Srisuma, Sorachai; Arikan, Meltem C; Bhattacharya, Soumyaroop; Rangasamy, Tirumalai; Bijli, Kaiser M; Rahman, Arshad; Crossno, Joseph T; Shapiro, Steven D; Mariani, Thomas J

2015-08-01

Chronic obstructive pulmonary disease (COPD) is a highly prevalent, chronic inflammatory lung disease with limited existing therapeutic options. While modulation of peroxisome proliferator-activating receptor (PPAR)-γ activity can modify inflammatory responses in several models of lung injury, the relevance of the PPARG pathway in COPD pathogenesis has not been previously explored. Mice lacking Pparg specifically in airway epithelial cells displayed increased susceptibility to chronic cigarette smoke (CS)-induced emphysema, with excessive macrophage accumulation associated with increased expression of chemokines, Ccl5, Cxcl10, and Cxcl15. Conversely, treatment of mice with a pharmacological PPARγ activator attenuated Cxcl10 and Cxcl15 expression and macrophage accumulation in response to CS. In vitro, CS increased lung epithelial cell chemokine expression in a PPARγ activation-dependent fashion. The ability of PPARγ to regulate CS-induced chemokine expression in vitro was not specifically associated with peroxisome proliferator response element (PPRE)-mediated transactivation activity but was correlated with PPARγ-mediated transrepression of NF-κB activity. Pharmacological or genetic activation of PPARγ activity abrogated CS-dependent induction of NF-κB activity. Regulation of NF-κB activity involved direct PPARγ-NF-κB interaction and PPARγ-mediated effects on IKK activation, IκBα degradation, and nuclear translocation of p65. Our data indicate that PPARG represents a disease-relevant pathophysiological and pharmacological target in COPD. Its activation state likely contributes to NF-κB-dependent, CS-induced chemokine-mediated regulation of inflammatory cell accumulation.

The novel ethylene-responsive factor CsERF025 affects the development of fruit bending in cucumber.

PubMed

Wang, Chunhua; Xin, Ming; Zhou, Xiuyan; Liu, Chunhong; Li, Shengnan; Liu, Dong; Xu, Yuan; Qin, Zhiwei

2017-11-01

Overexpression of CsERF025 induces fruit bending by promoting the production of ethylene. Cucumber fruit bending critically affects cucumber quality, but the mechanism that causes fruit bending remains unclear. To better understand this mechanism, we performed transcriptome analyses on tissues from the convex (C1) and concave (C2) sides of bending and straight (S) fruit at 2 days post anthesis (DPA). We identified a total of 281 differentially expressed genes (DEGs) from both the convex and concave sides of bent fruit that showed significantly different expression profiles relative to straight fruits. Of these 281 DEGs, 196 were up-regulated (C1/S_C2/S) and 85 were down-regulated (C1/S_C2/S). Among the 196 up-regulated DEGs, the transcriptional levels of genes related to ethylene biosynthesis and signaling pathways were significantly higher in bending fruit compared with straight fruit. CsERF025 showed the largest difference in expression between bending and straight fruit. CsERF025 is an AP2/ERF gene encoding a protein that localizes to the nucleus. Overexpression of this gene increased the bending rate of cucumber fruits and increased the angle of bending. CsERF025 increased both the expression of ethylene biosynthesis-related genes and the production of ethylene. The application of exogenous 1-aminocyclopropane-l-carboxylic acid (ACC) to straight fruits from control plants promoted fruit bending. Thus, CsERF025 enhances the production of ethylene and thereby promotes fruit bending in cucumber.

Platelet-rich plasma versus corticosteroid injection for recalcitrant lateral epicondylitis: clinical and ultrasonographic evaluation.

PubMed

Gautam, V K; Verma, Saurabh; Batra, Sahil; Bhatnagar, Nidhi; Arora, Sumit

2015-04-01

To evaluate the clinical and ultrasonographic changes in the morphology and vascularity of the common extensor tendon after injecting platelet-rich plasma (PRP) or corticosteroid (CS) for recalcitrant lateral epicondylitis (LE). 30 patients aged 18 to 60 years with recalcitrant (>6 months) LE not responsive to oral medication or non-invasive treatment were randomised to receive PRP (n=15) or CS (n=15) injection. Patients were assessed using the visual analogue scale (VAS) for pain, Disabilities of the Arm, Shoulder and Hand Scale (DASH) score, Oxford Elbow Score, modified Mayo Clinic performance index for the elbow (modified Mayo score), and hand grip strength. Ultrasonography was performed by a musculoskeletal ultrasonologist to evaluate for tear at the common extensor origin, oedema at the common extensor origin, cortical erosion, probe-induced tenderness, and thickness of the tendon. The VAS for pain, DASH score, Oxford Elbow Score, modified Mayo score, and hand grip strength all improved significantly from pre-injection to the 6-month follow-up in the PRP and CS groups. However, in the CS group, the scores generally peaked at 3 months and then deteriorated slightly at 6 months indicating recurrence of symptoms, which involved 46.7% of the CS patients. At 6 months, the number of patients positive for various ulrasonographic findings generally decreased. However, in the CS group, the number of patients with reduced thickness of the common extensor tendon increased from 2 to 12, and the number of patients with cortical erosion at the lateral epicondyle increased from 9 to 11. PRP appeared to enable biological healing of the lesion, whereas CS appeared to provide short-term, symptomatic relief but resulted in tendon degeneration.

Clinical outcomes of Ahmed glaucoma valve in anterior chamber versus ciliary sulcus.

PubMed

Bayer, A; Önol, M

2017-04-01

PurposeTo evaluate the outcomes of Ahmed glaucoma valve (AGV) tube insertion through the anterior chamber angle (ACA) or through the ciliary sulcus (CS).Patients and methodsIn this case-control study, we retrospectively reviewed the charts of consecutive glaucoma patients who had undergone AGV implantation either through the ACA or the CS between March 2009 and December 2014. The main outcome measures were intraocular pressure (IOP), number of glaucoma medications prescribed, best corrected visual acuity (BCVA), glaucoma type, success rate, complications, and survival ratios. Statistical analysis was carried out using SPSS.ResultsThere were 68 eyes in the ACA group and 35 eyes in the CS group. There were no significant differences between the groups for age, sex, laterality, IOP, preoperative glaucoma medication number, BCVA or glaucoma type (P>0.05). The postoperative follow-up period was 27.2±16.5 months and 30.2±17.7 months for the ACA and the CS groups (P=0.28); IOP values were significantly reduced at the last visit to 16.4±7.2 mm Hg and 14.4±6.8 mm Hg. The difference in the last-visit IOP between the groups was not significant (P=0.06), but the IOP reduction ratio was higher in the CS group (P=0.03). There was no significant difference in the number of postoperative medications (P=0.18). Postoperative complications were similar, but the incidence of flat anterior chamber was higher in the ACA group (P=0.05).ConclusionsThe use of an AGV can control IOP in the majority of cases whether placed in the ACA or the CS. The IOP reduction ratio seemed to be higher in the CS group.

Clinical outcomes of Ahmed glaucoma valve in anterior chamber versus ciliary sulcus

PubMed Central

Bayer, A; Önol, M

2017-01-01

Purpose To evaluate the outcomes of Ahmed glaucoma valve (AGV) tube insertion through the anterior chamber angle (ACA) or through the ciliary sulcus (CS). Patients and methods In this case-control study, we retrospectively reviewed the charts of consecutive glaucoma patients who had undergone AGV implantation either through the ACA or the CS between March 2009 and December 2014. The main outcome measures were intraocular pressure (IOP), number of glaucoma medications prescribed, best corrected visual acuity (BCVA), glaucoma type, success rate, complications, and survival ratios. Statistical analysis was carried out using SPSS. Results There were 68 eyes in the ACA group and 35 eyes in the CS group. There were no significant differences between the groups for age, sex, laterality, IOP, preoperative glaucoma medication number, BCVA or glaucoma type (P>0.05). The postoperative follow-up period was 27.2±16.5 months and 30.2±17.7 months for the ACA and the CS groups (P=0.28); IOP values were significantly reduced at the last visit to 16.4±7.2 mm Hg and 14.4±6.8 mm Hg. The difference in the last-visit IOP between the groups was not significant (P=0.06), but the IOP reduction ratio was higher in the CS group (P=0.03). There was no significant difference in the number of postoperative medications (P=0.18). Postoperative complications were similar, but the incidence of flat anterior chamber was higher in the ACA group (P=0.05). Conclusions The use of an AGV can control IOP in the majority of cases whether placed in the ACA or the CS. The IOP reduction ratio seemed to be higher in the CS group. PMID:27983734

The assessment of anorexia in patients with cancer: cut-off values for the FAACT-A/CS and the VAS for appetite.

PubMed

Blauwhoff-Buskermolen, S; Ruijgrok, C; Ostelo, R W; de Vet, H C W; Verheul, H M W; de van der Schueren, M A E; Langius, J A E

2016-02-01

Anorexia is a frequently observed symptom in patients with cancer and is associated with limited food intake and decreased quality of life. Diagnostic instruments such as the Anorexia/Cachexia Subscale (A/CS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire and the visual analog scale (VAS) for appetite have been recommended in the assessment of anorexia, but validated cut-off values are lacking. This study aimed to obtain cut-off values of these instruments for the assessment of anorexia in patients with cancer. The FAACT-A/CS and the VAS for appetite were administered to patients with cancer before start of chemotherapy. As reference standard for anorexia, two external criteria were used: (1) a cut-off value of ≥2 on the anorexia symptom scale of the EORTC QLQ C-30 and (2) the question "Do you experience a decreased appetite?" (yes/no). ROC curves were used to examine the optimal cut-off values for the FAACT-A/CS and VAS. A total of 273 patients (58 % male; 64.0 ± 10.6 years) were included. The median score on the FAACT-A/CS was 38 (IQR 32-42) points and 77 (IQR 47-93) points on the VAS. Considering both external criteria, the optimal cut-off value for the FAACT-A/CS was ≤37 (sensitivity (se) 80 %, specificity (sp) 81 %, positive predictive value (PV(+)) 79 %, negative predictive value (PV(-)) 82 %) and for the VAS was ≤70 (se 76 %, sp 83 %, PV(+) 80 %, PV(-) 79 %). For the assessment of anorexia in patients with cancer, our study suggests cut-off values of ≤37 for the FAACT-A/CS and ≤70 for the VAS. Future studies should confirm our findings in other patient samples.

An initiative to minimize amount of contrast media utilizing a novel rotational coronary sinus occlusive venography technique with ordinary cath-lab X-ray machine during CRT implantation.

PubMed

Al Fagih, Ahmed; Al Ghamdi, Saleh; El Tayeb, Areeg; Dagriri, Khaled

2010-09-01

Rotational angiography is one of the latest angiographic modalities to map the coronary venous tree anatomy. It provides a significant reduction in both contrast agent usage and radiation dose (up to 30%), without compromising the clinical utility of images. Hence, the present study was conducted to describe a new technique to minimize the amount of contrast media used during cardiac resynchronization therapy (CRT) implantation. The SL3 sheath was inserted into the right atrium via the femoral vein followed by withdrawal of the dilator. The tip of the sheath was manipulated to the vicinity of the coronary sinus (CS) ostium (OS). The CS was entered using a deflated balloon catheter. The sheath was then advanced gently beyond the CS OS. Occlusive venography was performed using 5-8 ml of contrast media in a rotational view starting from 45 degrees LAO to 0 degrees AP while holding the inflated balloon for a few seconds. Data from 30 consecutive patients who underwent CRT implantation were analyzed. The feasibility of rotational angiography, while occluding the CS with a specialized long, preshaped sheath and using an ordinary cath-lab imaging machine, was supported by the correctly delineated CS anatomy of all patients without any complications and death related to the placement of the CS catheters or sheaths. The mean contrast dose used for the entire procedure in all patients undergoing CRT was 14.76 +/- 6.8 ml. Use of rotational CS occlusive venography utilizing an ordinary cath-lab X-ray machine minimizes the use of contrast media during CRT implantation without compromising the visualized anatomy.

Comparison of visual outcomes after bilateral implantation of a diffractive trifocal intraocular lens and blended implantation of an extended depth of focus intraocular lens with a diffractive bifocal intraocular lens

PubMed Central

de Medeiros, André Lins; de Araújo Rolim, André Gustavo; Motta, Antonio Francisco Pimenta; Ventura, Bruna Vieira; Vilar, César; Chaves, Mário Augusto Pereira Dias; Carricondo, Pedro Carlos; Hida, Wilson Takashi

2017-01-01

Purpose The purpose of this study was to compare the visual outcomes and subjective visual quality between bilateral implantation of a diffractive trifocal intraocular lens, Alcon Acrysof IQ® PanOptix® TNFT00 (group A), and blended implantation of an extended depth of focus lens, J&J Tecnis Symfony® ZXR00 with a diffractive bifocal intraocular lens, J&J Vision Tecnis® ZMB00 (group B). Methods This prospective, nonrandomized, consecutive, comparative study included the assessment of 40 eyes in 20 patients implanted with multifocal intraocular lens. Exclusion criteria were existence of any corneal, retina, or optic nerve disease, previous eye surgery, illiteracy, previous refractive surgery, high axial myopia, expected postoperative corneal astigmatism of >1.00 cylindrical diopter (D), and intraoperative or postoperative complications. Binocular visual acuity was tested in all cases. Ophthalmological evaluation included the measurement of uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected near visual acuity (UNVA), and uncorrected intermediate visual acuity (UIVA), with the analysis of contrast sensitivity (CS), and visual defocus curve. Results Postoperative UDVA was 0.01 and −0.096 logMAR (p<0.01) in groups A and B, respectively; postoperative CDVA was −0.07 and −0.16 logMAR (p<0.01) in groups A and B, respectively; UIVA was 0.14 and 0.20 logMAR (p<0.01) in groups A and B, respectively; UNVA was −0.03 and 0.11 logMAR (p<0.01) in groups A and B, respectively. Under photopic conditions group B had better CS at low frequencies with and without glare. Conclusion Both groups promoted good quality of vision for long, intermediate, and short distances. Group B exhibited a better performance for very short distances and for intermediate and long distances ≥−1.50 D of vergence. Group A exhibited a better performance for UIVA at 60 cm and for UNVA at 40 cm. PMID:29138533

Visual-Cerebellar Pathways and Their Roles in the Control of Avian Flight.

PubMed

Wylie, Douglas R; Gutiérrez-Ibáñez, Cristián; Gaede, Andrea H; Altshuler, Douglas L; Iwaniuk, Andrew N

2018-01-01

In this paper, we review the connections and physiology of visual pathways to the cerebellum in birds and consider their role in flight. We emphasize that there are two visual pathways to the cerebellum. One is to the vestibulocerebellum (folia IXcd and X) that originates from two retinal-recipient nuclei that process optic flow: the nucleus of the basal optic root (nBOR) and the pretectal nucleus lentiformis mesencephali (LM). The second is to the oculomotor cerebellum (folia VI-VIII), which receives optic flow information, mainly from LM, but also local visual motion information from the optic tectum, and other visual information from the ventral lateral geniculate nucleus (Glv). The tectum, LM and Glv are all intimately connected with the pontine nuclei, which also project to the oculomotor cerebellum. We believe this rich integration of visual information in the cerebellum is important for analyzing motion parallax that occurs during flight. Finally, we extend upon a suggestion by Ibbotson (2017) that the hypertrophy that is observed in LM in hummingbirds might be due to an increase in the processing demands associated with the pathway to the oculomotor cerebellum as they fly through a cluttered environment while feeding.

Ideas and perspectives: truffles not radioactive

NASA Astrophysics Data System (ADS)

Büntgen, U.; Jäggi, M.; Stobbe, U.; Tegel, W.; Sproll, L.; Eikenberg, J.; Egli, S.

2015-11-01

Although ranging among the most expensive gourmet foods, it remains unclear if Burgundy truffles (Tuber aestivum) accumulate radioactivity at a harmful level comparable to other fungi. Here, we measure the 137Cs in 82 T. aestivum fruitbodies from Switzerland, Germany, France, Italy and Hungary. All specimens reveal insignificant radiocaesium concentrations, thus providing an all clear for truffle hunters and cultivators in Europe as well as dealers and customers from around the world. Our results are particularly relevant in the light of recent cultivation efforts and the fact that forest ecosystems are still highly contaminated with 137Cs, for which mushrooms are the main pathways to human diets.

Femtosecond laser-assisted LASIK versus PRK for high myopia: comparison of 18-month visual acuity and quality.

PubMed

Hashemi, Hassan; Ghaffari, Reza; Miraftab, Mohammad; Asgari, Soheila

2017-08-01

To compare 18-month outcomes between femtosecond laser-assisted LASIK (femto-LASIK) and photorefractive keratectomy with mitomycin-C (PRK-MMC) for myopia of more than 7.0 D in terms of visual acuity and quality. In this comparative nonrandomized clinical trial, 60 eyes from 30 patients (30 eyes in each group) were enrolled. The two procedures were compared in terms of 18-month changes in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction spherical equivalent, ocular and corneal higher order aberrations (HOAs), and contrast sensitivity (CS). Mean myopia was -8.65 ± 1.51 and -8.04 ± 1.70 D (P = 0.149) and mean ablation depth was 109.37 ± 9.07 and 105.09 ± 12.59 µm (P = 0.138), in the femto-LASIK and PRK-MMC groups, respectively. Baseline parameters were not significantly different between the two groups (all P > 0.05). At 18 months postoperatively, 75 % in the femto-LASIK, versus 57.1 % in the PRK-MMC group, had 20/20 UDVA (P = 0.017). CDVA remained similarly unchanged in both groups (P = 0.616). No case had residual refractive error more than 1.0 D in the femto-LASIK group, while 33.5 % in the other group had more than 1.0 D residual error (P = 0.390). Changes in corneal HOA were not significantly different between the two groups (P = 0.260). Cases in the femto-LASIK group showed more increase in ocular HOA (P = 0.032) and coma (P = 0.083, power = 72 %). CS remained similarly unchanged in all spatial frequencies in both groups (all P > 0.05). Although femto-LASIK induces more HOA compared to PRK-MMC, considering outcomes in terms of 20/20 UDVA, residual refractive error, and CS stability, femto-LASIK provides more favorable results than PRK-MMC in high myopia.

Matched optical quality comparison of 3-year results of PRK-MMC and phakic IOL implantation in the correction of high myopia.

PubMed

Miraftab, M; Hashemi, H; Asgari, S

2015-07-01

To compare 3-year results of PRK-MMC and phakic intraocular lens (PIOL) implantation in patients with >8.0 diopters (D) of myopia. This study was conducted as a non-randomized clinical trial on 23 eyes treated with PIOL (Artiflex; group A) and 23 eyes treated with PRK-MMC (group B). This report compares 3-year treatment results in these two groups. At 3 years after surgery, uncorrected visual acuity was 0.02±0.06 LogMAR in group A and 0.04±0.07 LogMAR in group B (P=0.639). Mean best corrected visual acuity in group A (0.004±0.02) was better than group B (0.03±0.07 LogMAR) (P=0.035). Mean manifest refraction spherical equivalent was -0.16±0.21 and -0.09±0.20D (P=0.190), respectively. Mesopic contrast sensitivity (CS) in the spatial frequency of three cycle/degree (CS3) significantly decreased in both groups, but the reduction was significantly higher in group B (P=0.024). CS6 decreased significantly only in group B (P=0.019). Changes in CS12 and CS18 showed no significant inter-group difference. In group A, the increase in C6 trefoil (0.16±0.18 μm, P=0.003) and reduction in spherical aberration (SA; 0.16±0.08 μm, P<0.001) were statistically significant. In group B, the reduction in vertical coma (P=0.052), and increases in horizontal coma (P=0.044), coma (P<0.001), SA (P<0.001), and total higher order aberrations (P<0.001) were significant after surgery. Based on 3-year results, PIOL implantation is a better choice than PRK-MMC for treating patients with >8.0D myopia. However, for patients with an inadequate aqueous depth, PRK-MMC can be an acceptable treatment option with a potential for decreased quality of vision.

Matched optical quality comparison of 3-year results of PRK–MMC and phakic IOL implantation in the correction of high myopia

PubMed Central

Miraftab, M; Hashemi, H; Asgari, S

2015-01-01

Aims To compare 3-year results of PRK–MMC and phakic intraocular lens (PIOL) implantation in patients with >8.0 diopters (D) of myopia. Methods This study was conducted as a non-randomized clinical trial on 23 eyes treated with PIOL (Artiflex; group A) and 23 eyes treated with PRK–MMC (group B). This report compares 3-year treatment results in these two groups. Results At 3 years after surgery, uncorrected visual acuity was 0.02±0.06 LogMAR in group A and 0.04±0.07 LogMAR in group B (P=0.639). Mean best corrected visual acuity in group A (0.004±0.02) was better than group B (0.03±0.07 LogMAR) (P=0.035). Mean manifest refraction spherical equivalent was −0.16±0.21 and −0.09±0.20D (P=0.190), respectively. Mesopic contrast sensitivity (CS) in the spatial frequency of three cycle/degree (CS3) significantly decreased in both groups, but the reduction was significantly higher in group B (P=0.024). CS6 decreased significantly only in group B (P=0.019). Changes in CS12 and CS18 showed no significant inter-group difference. In group A, the increase in C6 trefoil (0.16±0.18 μm, P=0.003) and reduction in spherical aberration (SA; 0.16±0.08 μm, P<0.001) were statistically significant. In group B, the reduction in vertical coma (P=0.052), and increases in horizontal coma (P=0.044), coma (P<0.001), SA (P<0.001), and total higher order aberrations (P<0.001) were significant after surgery. Conclusion Based on 3-year results, PIOL implantation is a better choice than PRK–MMC for treating patients with >8.0D myopia. However, for patients with an inadequate aqueous depth, PRK–MMC can be an acceptable treatment option with a potential for decreased quality of vision. PMID:25976638

Gene expression profile indicates involvement of NO in Camellia sinensis pollen tube growth at low temperature.

PubMed

Pan, Junting; Wang, Weidong; Li, Dongqin; Shu, Zaifa; Ye, Xiaoli; Chang, Pinpin; Wang, Yuhua

2016-10-18

Nitric oxide (NO) functions as a critical signaling molecule in the low-temperature stress responses in plants, including polarized pollen tube growth in Camellia sinensis. Despite this, the potential mechanisms underlying the participation of NO in pollen tube responses to low temperature remain unclear. Here, we investigate alterations to gene expression in C. sinensis pollen tubes exposed to low-temperature stress and NO using RNA-Seq technology, in order to find the potential candidate genes related to the regulation of pollen tube elongation by NO under low-temperature stress. Three libraries were generated from C. sinensis cv. 'Longjingchangye' pollen tubes cultured at 25 °C (CsPT-CK) and 4 °C (CsPT-LT) or with 25 μM DEA NONOate (CsPT-NO). The number of unigenes found for the three biological replications were 39,726, 40,440 and 41,626 for CsPT-CK; 36,993, 39,070 and 39,439 for CsPT-LT; and 39,514, 38,298 and 39,061 for CsPT-NO. A total of 36,097 unique assembled and annotated sequences from C. sinensis pollen tube reads were found in a BLAST search of the following databases: NCBI non-redundant nucleotide, Swiss-prot protein, Kyoto Encyclopedia of Genes and Genomes, Cluster of Orthologous Groups of proteins, and Gene Ontology. The absolute values of log 2 Ratio > 1 and probability > 0.7 were used as the thresholds for significantly differential gene expression, and 766, 497 and 929 differentially expressed genes (DEGs) were found from the comparison analyses of the CK-VS-LT, CK-VS-NO and LT-VS-NO libraries, respectively. Genes related to metabolism and signaling pathways of plant hormones, transcription factors (TFs), vesicle polarized trafficking, cell wall biosynthesis, the ubiquitination machinery of the ubiquitin system and species-specific secondary metabolite pathways were mainly observed in the CK-VS-LT and CK-VS-NO libraries. Differentially expressed unigenes related to the inhibition of C. sinensis pollen tube growth under low temperature and NO are identified in this study. The transcriptomic gene expression profiles present a valuable genomic tool to improve studying the molecular mechanisms underlying low-temperature tolerance in pollen tube.

Smelling directions: Olfaction modulates ambiguous visual motion perception

PubMed Central

Kuang, Shenbing; Zhang, Tao

2014-01-01

Senses of smells are often accompanied by simultaneous visual sensations. Previous studies have documented enhanced olfactory performance with concurrent presence of congruent color- or shape- related visual cues, and facilitated visual object perception when congruent smells are simultaneously present. These visual object-olfaction interactions suggest the existences of couplings between the olfactory pathway and the visual ventral processing stream. However, it is not known if olfaction can modulate visual motion perception, a function that is related to the visual dorsal stream. We tested this possibility by examining the influence of olfactory cues on the perceptions of ambiguous visual motion signals. We showed that, after introducing an association between motion directions and olfactory cues, olfaction could indeed bias ambiguous visual motion perceptions. Our result that olfaction modulates visual motion processing adds to the current knowledge of cross-modal interactions and implies a possible functional linkage between the olfactory system and the visual dorsal pathway. PMID:25052162

Multisensory training can promote or impede visual perceptual learning of speech stimuli: visual-tactile vs. visual-auditory training.

PubMed

Eberhardt, Silvio P; Auer, Edward T; Bernstein, Lynne E

2014-01-01

In a series of studies we have been investigating how multisensory training affects unisensory perceptual learning with speech stimuli. Previously, we reported that audiovisual (AV) training with speech stimuli can promote auditory-only (AO) perceptual learning in normal-hearing adults but can impede learning in congenitally deaf adults with late-acquired cochlear implants. Here, impeder and promoter effects were sought in normal-hearing adults who participated in lipreading training. In Experiment 1, visual-only (VO) training on paired associations between CVCVC nonsense word videos and nonsense pictures demonstrated that VO words could be learned to a high level of accuracy even by poor lipreaders. In Experiment 2, visual-auditory (VA) training in the same paradigm but with the addition of synchronous vocoded acoustic speech impeded VO learning of the stimuli in the paired-associates paradigm. In Experiment 3, the vocoded AO stimuli were shown to be less informative than the VO speech. Experiment 4 combined vibrotactile speech stimuli with the visual stimuli during training. Vibrotactile stimuli were shown to promote visual perceptual learning. In Experiment 5, no-training controls were used to show that training with visual speech carried over to consonant identification of untrained CVCVC stimuli but not to lipreading words in sentences. Across this and previous studies, multisensory training effects depended on the functional relationship between pathways engaged during training. Two principles are proposed to account for stimulus effects: (1) Stimuli presented to the trainee's primary perceptual pathway will impede learning by a lower-rank pathway. (2) Stimuli presented to the trainee's lower rank perceptual pathway will promote learning by a higher-rank pathway. The mechanisms supporting these principles are discussed in light of multisensory reverse hierarchy theory (RHT).

Tactile spatial working memory activates the dorsal extrastriate cortical pathway in congenitally blind individuals.

PubMed

Bonino, D; Ricciardi, E; Sani, L; Gentili, C; Vanello, N; Guazzelli, M; Vecchi, T; Pietrini, P

2008-09-01

In sighted individuals, both the visual and tactile version of the same spatial working memory task elicited neural responses in the dorsal "where" cortical pathway (Ricciardi et al., 2006). Whether the neural response during the tactile working memory task is due to visually-based spatial imagery or rather reflects a more abstract, supramodal organization of the dorsal cortical pathway remains to be determined. To understand the role of visual experience on the functional organization of the dorsal cortical stream, using functional magnetic resonance imaging (fMRI) here we examined brain response in four individuals with congenital or early blindness and no visual recollection, while they performed the same tactile spatial working memory task, a one-back recognition of 2D and 3D matrices. The blind subjects showed a significant activation in bilateral posterior parietal cortex, dorsolateral and inferior prefrontal areas, precuneus, lateral occipital cortex, and cerebellum. Thus, dorsal occipito-parietal areas are involved in mental imagery dealing with spatial components in subjects without prior visual experience and in response to a non-visual task. These data indicate that recruitment of the dorsal cortical pathway in response to the tactile spatial working memory task is not mediated by visually-based imagery and that visual experience is not a prerequisite for the development of a more abstract functional organization of the dorsal stream. These findings, along with previous data indicating a similar supramodal functional organization within the ventral cortical pathway and the motion processing brain regions, may contribute to explain how individuals who are born deprived of sight are able to interact effectively with the surrounding world.

Multisensory training can promote or impede visual perceptual learning of speech stimuli: visual-tactile vs. visual-auditory training

PubMed Central

Eberhardt, Silvio P.; Auer Jr., Edward T.; Bernstein, Lynne E.

2014-01-01

In a series of studies we have been investigating how multisensory training affects unisensory perceptual learning with speech stimuli. Previously, we reported that audiovisual (AV) training with speech stimuli can promote auditory-only (AO) perceptual learning in normal-hearing adults but can impede learning in congenitally deaf adults with late-acquired cochlear implants. Here, impeder and promoter effects were sought in normal-hearing adults who participated in lipreading training. In Experiment 1, visual-only (VO) training on paired associations between CVCVC nonsense word videos and nonsense pictures demonstrated that VO words could be learned to a high level of accuracy even by poor lipreaders. In Experiment 2, visual-auditory (VA) training in the same paradigm but with the addition of synchronous vocoded acoustic speech impeded VO learning of the stimuli in the paired-associates paradigm. In Experiment 3, the vocoded AO stimuli were shown to be less informative than the VO speech. Experiment 4 combined vibrotactile speech stimuli with the visual stimuli during training. Vibrotactile stimuli were shown to promote visual perceptual learning. In Experiment 5, no-training controls were used to show that training with visual speech carried over to consonant identification of untrained CVCVC stimuli but not to lipreading words in sentences. Across this and previous studies, multisensory training effects depended on the functional relationship between pathways engaged during training. Two principles are proposed to account for stimulus effects: (1) Stimuli presented to the trainee’s primary perceptual pathway will impede learning by a lower-rank pathway. (2) Stimuli presented to the trainee’s lower rank perceptual pathway will promote learning by a higher-rank pathway. The mechanisms supporting these principles are discussed in light of multisensory reverse hierarchy theory (RHT). PMID:25400566

Objective Assessment of Activity Limitation in Glaucoma with Smartphone Virtual Reality Goggles: A Pilot Study.

PubMed

Goh, Rachel L Z; Kong, Yu Xiang George; McAlinden, Colm; Liu, John; Crowston, Jonathan G; Skalicky, Simon E

2018-01-01

To evaluate the use of smartphone-based virtual reality to objectively assess activity limitation in glaucoma. Cross-sectional study of 93 patients (54 mild, 22 moderate, 17 severe glaucoma). Sociodemographics, visual parameters, Glaucoma Activity Limitation-9 and Visual Function Questionnaire - Utility Index (VFQ-UI) were collected. Mean age was 67.4 ± 13.2 years; 52.7% were male; 65.6% were driving. A smartphone placed inside virtual reality goggles was used to administer the Virtual Reality Glaucoma Visual Function Test (VR-GVFT) to participants, consisting of three parts: stationary, moving ball, driving. Rasch analysis and classical validity tests were conducted to assess performance of VR-GVFT. Twenty-four of 28 stationary test items showed acceptable fit to the Rasch model (person separation 3.02, targeting 0). Eleven of 12 moving ball test items showed acceptable fit (person separation 3.05, targeting 0). No driving test items showed acceptable fit. Stationary test person scores showed good criterion validity, differentiating between glaucoma severity groups ( P = 0.014); modest convergence validity, with mild to moderate correlation with VFQ-UI, better eye (BE) mean deviation, BE pattern deviation, BE central scotoma, worse eye (WE) visual acuity, and contrast sensitivity (CS) in both eyes ( R = 0.243-0.381); and suboptimal divergent validity. Multivariate analysis showed that lower WE CS ( P = 0.044) and greater age ( P = 0.009) were associated with worse stationary test person scores. Smartphone-based virtual reality may be a portable objective simulation test of activity limitation related to glaucomatous visual loss. The use of simulated virtual environments could help better understand the activity limitations that affect patients with glaucoma.

Objective Assessment of Activity Limitation in Glaucoma with Smartphone Virtual Reality Goggles: A Pilot Study

PubMed Central

Goh, Rachel L. Z.; McAlinden, Colm; Liu, John; Crowston, Jonathan G.; Skalicky, Simon E.

2018-01-01

Purpose To evaluate the use of smartphone-based virtual reality to objectively assess activity limitation in glaucoma. Methods Cross-sectional study of 93 patients (54 mild, 22 moderate, 17 severe glaucoma). Sociodemographics, visual parameters, Glaucoma Activity Limitation-9 and Visual Function Questionnaire – Utility Index (VFQ-UI) were collected. Mean age was 67.4 ± 13.2 years; 52.7% were male; 65.6% were driving. A smartphone placed inside virtual reality goggles was used to administer the Virtual Reality Glaucoma Visual Function Test (VR-GVFT) to participants, consisting of three parts: stationary, moving ball, driving. Rasch analysis and classical validity tests were conducted to assess performance of VR-GVFT. Results Twenty-four of 28 stationary test items showed acceptable fit to the Rasch model (person separation 3.02, targeting 0). Eleven of 12 moving ball test items showed acceptable fit (person separation 3.05, targeting 0). No driving test items showed acceptable fit. Stationary test person scores showed good criterion validity, differentiating between glaucoma severity groups (P = 0.014); modest convergence validity, with mild to moderate correlation with VFQ-UI, better eye (BE) mean deviation, BE pattern deviation, BE central scotoma, worse eye (WE) visual acuity, and contrast sensitivity (CS) in both eyes (R = 0.243–0.381); and suboptimal divergent validity. Multivariate analysis showed that lower WE CS (P = 0.044) and greater age (P = 0.009) were associated with worse stationary test person scores. Conclusions Smartphone-based virtual reality may be a portable objective simulation test of activity limitation related to glaucomatous visual loss. Translational Relevance The use of simulated virtual environments could help better understand the activity limitations that affect patients with glaucoma. PMID:29372112

Visual performance after conventional LASIK and wavefront-guided LASIK with iris-registration: results at 1 year

PubMed Central

Zhang, Jing; Zhou, Yue-Hua; Li, Rui; Tian, Lei

2013-01-01

AIM To compare visual performance of wavefront-guided laser in situ keratomileusis (LASIK) with iris-registration (Wg-LASIK group) and conventional LASIK (LASIK group) one year after surgery and analyze the correlation between wavefront aberrations and visual performance. METHODS Eight hundred and fifty-two myopic eyes of 430 patients were enrolled in this prospective study and divided into two groups: Wg-LASIK group (436 eyes) and LASIK group (416 eyes). A Wavescan Wavefront aberrometer was used to analyze Zernike coefficients and the root-mean-square (RMS) of higher order aberrations, and Optec 6500 visual function instrument was used to measure contrast sensitivity (CS) before and 3, 6, 12 months after surgery. RESULTS The mean spherical equivalent (SE) in Wg-LASIK group was significantly better than those in LASIK group one year after surgery (P=0.024). Wg-LASIK eyes showed better CS values than LASIK eyes at all spatial frequencies with and without glare after surgery (P all<0.01). Moreover, the increase of higher RMS (RMSh), coma, RMS3, RMS4, RMS5 in Wg-LASIK group were significantly lower than those in LASIK group 1 year after surgery (P all<0.05). The increase of coma, spherical aberration (SA), RMS3 and RMS4 in Wg-LASIK and coma and RMS3 in LASIK group were negatively correlated with reduction of contrast sensitivity 1 year after surgery. CONCLUSION A significant better visual performance is got in Wg-LASIK group compared with LASIK group 1 year after surgery, and the Wg-LASIK is particularly suitable for eyes with high-magnitude RMSh. PMID:23991386

Subcellular proteome profiles of different latex fractions revealed washed solutions from rubber particles contain crucial enzymes for natural rubber biosynthesis.

PubMed

Wang, Dan; Sun, Yong; Chang, Lili; Tong, Zheng; Xie, Quanliang; Jin, Xiang; Zhu, Liping; He, Peng; Li, Hongbin; Wang, Xuchu

2018-06-30

Rubber particle (RP) is a specific organelle for natural rubber biosynthesis (NRB) and storage in rubber tree Hevea brasiliensis. NRB is processed by RP membrane-localized proteins, which were traditionally purified by repeated washing. However, we noticed many proteins in the discarded washing solutions (WS) from RP. Here, we compared the proteome profiles of WS, C-serum (CS) and RP by 2-DE, and identified 233 abundant proteins from WS by mass spectrometry. Many spots on 2-DE gels were identified as different protein species. We further performed shotgun analysis of CS, WS and RP and identified 1837, 1799 and 1020 unique proteins, respectively. Together with 2-DE, we finally identified 1825 proteins from WS, 246 were WS-specific. These WS-specific proteins were annotated in Gene Ontology, indicating most abundant pathways are organic substance metabolic process, protein degradation, primary metabolic process, and energy metabolism. Protein-protein interaction analysis revealed these WS-specific proteins are mainly involved in ribosomal metabolism, proteasome system, vacuolar protein sorting and endocytosis. Label free and Western blotting revealed many WS-specific proteins and protein complexes are crucial for NRB initiation. These findings not only deepen our understanding of WS proteome, but also provide new evidences on the roles of RP membrane proteins in NRB. Natural rubber is stored in rubber particle from the rubber tree. Rubber particles were traditionally purified by repeated washing, but many proteins were identified from the washing solutions (WS). We obtained the first visualization proteome profiles with 1825 proteins from WS, including 246 WS-specific ones. These WS proteins contain almost all enzymes for polyisoprene initiation and may play important roles in rubber biosynthesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Grohar: Automated Visualization of Genome-Scale Metabolic Models and Their Pathways.

PubMed

Moškon, Miha; Zimic, Nikolaj; Mraz, Miha

2018-05-01

Genome-scale metabolic models (GEMs) have become a powerful tool for the investigation of the entire metabolism of the organism in silico. These models are, however, often extremely hard to reconstruct and also difficult to apply to the selected problem. Visualization of the GEM allows us to easier comprehend the model, to perform its graphical analysis, to find and correct the faulty relations, to identify the parts of the system with a designated function, etc. Even though several approaches for the automatic visualization of GEMs have been proposed, metabolic maps are still manually drawn or at least require large amount of manual curation. We present Grohar, a computational tool for automatic identification and visualization of GEM (sub)networks and their metabolic fluxes. These (sub)networks can be specified directly by listing the metabolites of interest or indirectly by providing reference metabolic pathways from different sources, such as KEGG, SBML, or Matlab file. These pathways are identified within the GEM using three different pathway alignment algorithms. Grohar also supports the visualization of the model adjustments (e.g., activation or inhibition of metabolic reactions) after perturbations are induced.

PaintOmics 3: a web resource for the pathway analysis and visualization of multi-omics data.

PubMed

Hernández-de-Diego, Rafael; Tarazona, Sonia; Martínez-Mira, Carlos; Balzano-Nogueira, Leandro; Furió-Tarí, Pedro; Pappas, Georgios J; Conesa, Ana

2018-05-25

The increasing availability of multi-omic platforms poses new challenges to data analysis. Joint visualization of multi-omics data is instrumental in better understanding interconnections across molecular layers and in fully utilizing the multi-omic resources available to make biological discoveries. We present here PaintOmics 3, a web-based resource for the integrated visualization of multiple omic data types onto KEGG pathway diagrams. PaintOmics 3 combines server-end capabilities for data analysis with the potential of modern web resources for data visualization, providing researchers with a powerful framework for interactive exploration of their multi-omics information. Unlike other visualization tools, PaintOmics 3 covers a comprehensive pathway analysis workflow, including automatic feature name/identifier conversion, multi-layered feature matching, pathway enrichment, network analysis, interactive heatmaps, trend charts, and more. It accepts a wide variety of omic types, including transcriptomics, proteomics and metabolomics, as well as region-based approaches such as ATAC-seq or ChIP-seq data. The tool is freely available at www.paintomics.org.

Signals of threat do not capture, but prioritize, attention: a conditioning approach.

PubMed

Notebaert, Lies; Crombez, Geert; Van Damme, Stefaan; De Houwer, Jan; Theeuwes, Jan

2011-02-01

Research suggests that threatening information captures attention more rapidly than neutral information. However, in most studies threat stimuli differ perceptually from neutral stimuli and are instrumental to perform the task, leaving the question unanswered whether threat is sufficient to capture attention. In experiment 1, we designed a visual search task with stimuli of equal salience (colored circles) that have the potential to lead to efficient search (10 ms/item). In experiment 2, one of the colors (conditioned stimulus, CS+) was made threatening by means of fear conditioning. Participants responded to a target presented in one of the circles. Overall, the search was faster on congruent trials (where the target was presented in the CS+) than on baseline trials (where the CS + was absent). Furthermore, the search was slower on incongruent trials (where the target was presented in another color than the CS+) than on baseline trials. The search on congruent trials was affected by set size (90 ms/item), but to a lesser extent than on baseline trials (105 ms/item). We conclude that threat prioritizes, but does not capture attention. PsycINFO Database Record (c) 2011 APA, all rights reserved.

Formation of magnetic discontinuities through viscous relaxation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Sanjay; Bhattacharyya, R.; Smolarkiewicz, P. K.

2014-05-15

According to Parker's magnetostatic theorem, tangential discontinuities in magnetic field, or current sheets (CSs), are generally unavoidable in an equilibrium magnetofluid with infinite electrical conductivity and complex magnetic topology. These CSs are due to a failure of a magnetic field in achieving force-balance everywhere and preserving its topology while remaining in a spatially continuous state. A recent work [Kumar, Bhattacharyya, and Smolarkiewicz, Phys. Plasmas 20, 112903 (2013)] demonstrated this CS formation utilizing numerical simulations in terms of the vector magnetic field. The magnetohydrodynamic simulations presented here complement the above work by demonstrating CS formation by employing a novel approach ofmore » describing the magnetofluid evolution in terms of magnetic flux surfaces instead of the vector magnetic field. The magnetic flux surfaces being the possible sites on which CSs develop, this approach provides a direct visualization of the CS formation, helpful in understanding the governing dynamics. The simulations confirm development of tangential discontinuities through a favorable contortion of magnetic flux surfaces, as the magnetofluid undergoes a topology-preserving viscous relaxation from an initial non-equilibrium state with twisted magnetic field. A crucial finding of this work is in its demonstration of CS formation at spatial locations away from the magnetic nulls.« less

Improved Compressive Sensing of Natural Scenes Using Localized Random Sampling

PubMed Central

Barranca, Victor J.; Kovačič, Gregor; Zhou, Douglas; Cai, David

2016-01-01

Compressive sensing (CS) theory demonstrates that by using uniformly-random sampling, rather than uniformly-spaced sampling, higher quality image reconstructions are often achievable. Considering that the structure of sampling protocols has such a profound impact on the quality of image reconstructions, we formulate a new sampling scheme motivated by physiological receptive field structure, localized random sampling, which yields significantly improved CS image reconstructions. For each set of localized image measurements, our sampling method first randomly selects an image pixel and then measures its nearby pixels with probability depending on their distance from the initially selected pixel. We compare the uniformly-random and localized random sampling methods over a large space of sampling parameters, and show that, for the optimal parameter choices, higher quality image reconstructions can be consistently obtained by using localized random sampling. In addition, we argue that the localized random CS optimal parameter choice is stable with respect to diverse natural images, and scales with the number of samples used for reconstruction. We expect that the localized random sampling protocol helps to explain the evolutionarily advantageous nature of receptive field structure in visual systems and suggests several future research areas in CS theory and its application to brain imaging. PMID:27555464

The cervical vertebral maturation method: A user's guide.

PubMed

McNamara, James A; Franchi, Lorenzo

2018-03-01

The cervical vertebral maturation (CVM) method is used to determine the craniofacial skeletal maturational stage of an individual at a specific time point during the growth process. This diagnostic approach uses data derived from the second (C2), third (C3), and fourth (C4) cervical vertebrae, as visualized in a two-dimensional lateral cephalogram. Six maturational stages of those three cervical vertebrae can be determined, based on the morphology of their bodies. The first step is to evaluate the inferior border of these vertebral bodies, determining whether they are flat or concave (ie, presence of a visible notch). The second step in the analysis is to evaluate the shape of C3 and C4. These vertebral bodies change in shape in a typical sequence, progressing from trapezoidal to rectangular horizontal, to square, and to rectangular vertical. Typically, cervical stages (CSs) 1 and CS 2 are considered prepubertal, CS 3 and CS 4 circumpubertal, and CS 5 and CS 6 postpubertal. Criticism has been rendered as to the reproducibility of the CVM method. Diminished reliability may be observed at least in part due to the lack of a definitive description of the staging procedure in the literature. Based on the now nearly 20 years of experience in staging cervical vertebrae, this article was prepared as a "user's guide" that describes the CVM stages in detail in attempt to help the reader use this approach in everyday clinical practice.

Interrelationship and limitations of conventional radiographic assessments of skeletal maturation.

PubMed

Shim J, Jocelyne; Bogowicz, Paul; Heo, Giseon; Lagravère, Manuel O

2012-06-01

Assessments of skeletal maturation (ASM) are used by clinicians to optimize treatments for each patient. This study examines the interrelationship between and limitations of hand-wrist and cervical vertebrae maturation methods in adolescent patients. Radiographs (hand-wrist and lateral cephalometric) were obtained from patients (n=62, 11 to 17 years of age) at two-time periods (T1/T2) with time intervals of 9.75 to 16.50 months. Radiographs were scored using cervical vertebral maturation staging (CS) and Fishman's skeletal maturation indices (SMI). Functional data analysis was used to visually assess maturational changes of the cervical vertebrae. Both SMI and CS increased over the period of observation. Age was moderately correlated with SMI (0.707/0.651 at T1/T2) and mildly correlated with CS (0.431/0.314 at T1/T2). There was some evidence of gender variability in SMI. The correlations between SMI and CS were 0.513 and 0.372 at T1 and T2, respectively. Functional data analysis illustrated the difficulty in differentiating contiguous cervical stages. Discrepancies exist between both scoring methods. Further studies are needed to overcome the difficulties encountered with CS. Clinicians are advised to use ASM methods with caution in adolescent patients given the aforementioned discrepancies. Separate references for boys and girls are not required. Copyright © 2012. Published by Elsevier Masson SAS.

A new neural framework for visuospatial processing.

PubMed

Kravitz, Dwight J; Saleem, Kadharbatcha S; Baker, Chris I; Mishkin, Mortimer

2011-04-01

The division of cortical visual processing into distinct dorsal and ventral streams is a key framework that has guided visual neuroscience. The characterization of the ventral stream as a 'What' pathway is relatively uncontroversial, but the nature of dorsal stream processing is less clear. Originally proposed as mediating spatial perception ('Where'), more recent accounts suggest it primarily serves non-conscious visually guided action ('How'). Here, we identify three pathways emerging from the dorsal stream that consist of projections to the prefrontal and premotor cortices, and a major projection to the medial temporal lobe that courses both directly and indirectly through the posterior cingulate and retrosplenial cortices. These three pathways support both conscious and non-conscious visuospatial processing, including spatial working memory, visually guided action and navigation, respectively.

PyPathway: Python Package for Biological Network Analysis and Visualization.

PubMed

Xu, Yang; Luo, Xiao-Chun

2018-05-01

Life science studies represent one of the biggest generators of large data sets, mainly because of rapid sequencing technological advances. Biological networks including interactive networks and human curated pathways are essential to understand these high-throughput data sets. Biological network analysis offers a method to explore systematically not only the molecular complexity of a particular disease but also the molecular relationships among apparently distinct phenotypes. Currently, several packages for Python community have been developed, such as BioPython and Goatools. However, tools to perform comprehensive network analysis and visualization are still needed. Here, we have developed PyPathway, an extensible free and open source Python package for functional enrichment analysis, network modeling, and network visualization. The network process module supports various interaction network and pathway databases such as Reactome, WikiPathway, STRING, and BioGRID. The network analysis module implements overrepresentation analysis, gene set enrichment analysis, network-based enrichment, and de novo network modeling. Finally, the visualization and data publishing modules enable users to share their analysis by using an easy web application. For package availability, see the first Reference.

Integrating multi-omics analyses of Nonomuraea dietziae to reveal the role of soybean oil in [(4'-OH)MeLeu]4-CsA overproduction.

PubMed

Liu, Huanhuan; Huang, Di; Jin, Lina; Wang, Cheng; Liang, Shaoxiong; Wen, Jianping

2017-07-14

Nonomuraea dietziae is a promising microorganism to mediate the region-specific monooxygenation reaction of cyclosporine A (CsA). The main product [(4'-OH)MeLeu] 4 -CsA possesses high anti-HIV/HCV and hair growth-stimulating activities while avoiding the immunosuppressive effect of CsA. However, the low conversion efficiency restricts the clinical application. In this study, the production of [(4'-OH)MeLeu] 4 -CsA was greatly improved by 55.6% from 182.8 to 284.4 mg/L when supplementing soybean oil into the production medium, which represented the highest production of [(4'-OH)MeLeu] 4 -CsA so far. To investigate the effect of soybean oil on CsA conversion, some other plant oils (corn oil and peanut oil) and the major hydrolysates of soybean oil were fed into the production medium, respectively. The results demonstrated that the plant oils, rather than the hydrolysates, could significantly improve the [(4'-OH)MeLeu] 4 -CsA production, suggesting that soybean oil might not play its role in the lipid metabolic pathway. To further unveil the mechanism of [(4'-OH)MeLeu] 4 -CsA overproduction under the soybean oil condition, a proteomic analysis based on the two-dimensional gel electrophoresis coupled with MALDI TOF/TOF mass spectrometry was implemented. The results showed that central carbon metabolism, genetic information processing and energy metabolism were significantly up-regulated under the soybean oil condition. Moreover, the gas chromatography-mass spectrometry-based metabolomic analysis indicated that soybean oil had a great effect on amino acid metabolism and tricarboxylic acid cycle. In addition, the transcription levels of cytochrome P450 hydroxylase (CYP) genes for CsA conversion were determined by RT-qPCR and the results showed that most of the CYP genes were up-regulated under the soybean oil condition. These findings indicate that soybean oil could strengthen the primary metabolism and the CYP system to enhance the mycelium growth and the monooxygenation reaction, respectively, and it will be a guidance for the further metabolic engineering of this strain.

Cucumber (Cucumis sativus L.) Nitric Oxide Synthase Associated Gene1 (CsNOA1) Plays a Role in Chilling Stress

PubMed Central

Liu, Xingwang; Liu, Bin; Xue, Shudan; Cai, Yanlinq; Qi, Wenzhu; Jian, Chen; Xu, Shuo; Wang, Ting; Ren, Huazhong

2016-01-01

Nitric oxide (NO) is a gaseous signaling molecule in plants, transducing information as a result of exposure to low temperatures. However, the underlying molecular mechanism linking NO with chilling stress is not well understood. Here, we functionally characterized the cucumber (Cucumis sativus L.) nitric oxide synthase-associated gene, NITRIC OXIDE ASSOCIATED 1 (CsNOA1). Expression analysis of CsNOA1, using quantitative real-time PCR, in situ hybridization, and a promoter::β-glucuronidase (GUS) reporter assay, revealed that it is expressed mainly in the root and shoot apical meristem (SAM), and that expression is up-regulated by low temperatures. A CsNOA1-GFP fusion protein was found to be localized in the mitochondria, and ectopic expression of CsNOA1 in the A. thaliana noa1 mutant partially rescued the normal phenotype. When overexpressing CsNOA1 in the Atnoa1 mutant under normal condition, no obvious phenotypic differences was observed between its wild type and transgenic plants. However, the leaves from mutant plant grown under chilling conditions showed hydrophanous spots and wilting. Physiology tolerance markers, chlorophyll fluorescence parameter (Fv/Fm), and electrolyte leakage, were observed to dramatically change, compared mutant to overexpressing lines. Transgenic cucumber plants revealed that the gene is required by seedlings to tolerate chilling stress: constitutive over-expression of CsNOA1 led to a greater accumulation of soluble sugars, starch, and an up-regulation of Cold-regulatory C-repeat binding factor3 (CBF3) expression as well as a lower chilling damage index (CI). Conversely, suppression of CsNOA1 expression resulted in the opposite phenotype and a reduced NO content compared to wild type plants. Those results suggest that CsNOA1 regulates cucumber seedlings chilling tolerance. Additionally, under normal condition, we took several classic inhibitors to perform, and detect endogenous NO levels in wild type cucumber seedling. The results suggest that generation of endogenous NO in cucumber leaves occurs largely independently in the (CsNOA1) and nitrate reductase (NR) pathway. PMID:27891134

It's all connected: Pathways in visual object recognition and early noun learning.

PubMed

Smith, Linda B

2013-11-01

A developmental pathway may be defined as the route, or chain of events, through which a new structure or function forms. For many human behaviors, including object name learning and visual object recognition, these pathways are often complex and multicausal and include unexpected dependencies. This article presents three principles of development that suggest the value of a developmental psychology that explicitly seeks to trace these pathways and uses empirical evidence on developmental dependencies among motor development, action on objects, visual object recognition, and object name learning in 12- to 24-month-old infants to make the case. The article concludes with a consideration of the theoretical implications of this approach. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Trichome-Related Mutants Provide a New Perspective on Multicellular Trichome Initiation and Development in Cucumber (Cucumis sativus L)

PubMed Central

Liu, Xingwang; Bartholomew, Ezra; Cai, Yanling; Ren, Huazhong

2016-01-01

Trichomes are specialized epidermal cells located in aerial parts of plants that function in plant defense against biotic and abiotic stresses. The simple unicellular trichomes of Arabidopsis serve as an excellent model to study the molecular mechanism of cell differentiation and pattern formation in plants. Loss-of-function mutations in Arabidopsis thaliana have suggested that the core genes GL1 (which encodes a MYB transcription factor) and TTG1 (which encodes a WD40 repeat-containing protein) are important for the initiation and spacing of leaf trichomes, while for normal trichome initiation, the genes GL3, and EGL3 (which encode a bHLH protein) are needed. However, the positive regulatory genes involved in multicellular trichrome development in cucumber remain unclear. This review focuses on the phenotype of mutants (csgl3, tril, tbh, mict, and csgl1) with disturbed trichomes in cucumber and then infers which gene(s) play key roles in trichome initiation and development in those mutants. Evidence indicates that MICT, TBH, and CsGL1 are allelic with alternative splicing. CsGL3 and TRIL are allelic and override the effect of TBH, MICT, and CsGL1 on the regulation of multicellular trichome development; and affect trichome initiation. CsGL3, TRIL, MICT, TBH, and CsGL1 encode HD-Zip proteins with different subfamilies. Genetic and molecular analyses have revealed that CsGL3, TRIL, MICT, TBH, and CsGL1 are responsible for the differentiation of epidermal cells and the development of trichomes. Based on current knowledge, a positive regulator pathway model for trichome development in cucumber was proposed and compared to a model in Arabidopsis. These data suggest that trichome development in cucumber may differ from that in Arabidopsis. PMID:27559338

Elevated Urinary Levels of 8-Hydroxy-2'-deoxyguanosine in a Japanese Child of Xeroderma Pigmentosum/Cockayne Syndrome Complex with Infantile Onset of Nephrotic Syndrome.

PubMed

Kondo, Daiki; Noguchi, Atsuko; Tamura, Hiroaki; Tsuchida, Satoko; Takahashi, Ikuko; Kubota, Hiroki; Yano, Tamami; Oyama, Chikako; Sawaishi, Yukio; Moriwaki, Shinichi; Takahashi, Tsutomu

2016-07-01

Nucleotide excision repair (NER) is an essential biological pathway protecting against ultraviolet light-induced DNA damage. Deficient NER causes a group of rare genetic disorders including two autosomal recessive diseases, xeroderma pigmentosum (XP) and Cockayne syndrome (CS). In addition to the cutaneous photosensitivity shared in XP and CS, CS is featured by growth failure, neurological deterioration, microcephaly, and deep sunken eyes. XP/CS complex is an extremely rare type of NER disorder with a distinct phenotype that is characterized by the skin and eye pathology of XP and the somatic and neurological abnormalities of CS. Some of CS cases have been reported to be complicated with renal failure, but the genetic background or the etiology of the renal failure has not been reported. We herein report a 1-year-old Japanese boy with XP/CS complex, complicated by nephrotic syndrome. Diagnosis was confirmed by the presence of compound heterozygous mutations, G47R (c.139G>A) and R616G (c.1846C>G), in the excision repair cross-complementation group 2 (ERCC2) gene. The kidney biopsies, performed at the age of 1 year and 2 months, revealed diffuse expansion of the mesangial matrix and segmental glomerulosclerosis under light microscopy, and diffused thin capillary walls with partially lamellated regions under electron microscopy. Notably, high levels of urinary 8-hydroxy-2'-deoxyguanosin, known as an oxidative stress marker, were observed during the clinical course. The patient died at the age of 1 year and 11 months because of renal failure. We suggest the involvement of oxidative stress in the pathogenesis of nephrotic syndrome in NER disorders.

Activation of the Human MT Complex by Motion in Depth Induced by a Moving Cast Shadow

PubMed Central

Katsuyama, Narumi; Usui, Nobuo; Taira, Masato

2016-01-01

A moving cast shadow is a powerful monocular depth cue for motion perception in depth. For example, when a cast shadow moves away from or toward an object in a two-dimensional plane, the object appears to move toward or away from the observer in depth, respectively, whereas the size and position of the object are constant. Although the cortical mechanisms underlying motion perception in depth by cast shadow are unknown, the human MT complex (hMT+) is likely involved in the process, as it is sensitive to motion in depth represented by binocular depth cues. In the present study, we examined this possibility by using a functional magnetic resonance imaging (fMRI) technique. First, we identified the cortical regions sensitive to the motion of a square in depth represented via binocular disparity. Consistent with previous studies, we observed significant activation in the bilateral hMT+, and defined functional regions of interest (ROIs) there. We then investigated the activity of the ROIs during observation of the following stimuli: 1) a central square that appeared to move back and forth via a moving cast shadow (mCS); 2) a segmented and scrambled cast shadow presented beside the square (sCS); and 3) no cast shadow (nCS). Participants perceived motion of the square in depth in the mCS condition only. The activity of the hMT+ was significantly higher in the mCS compared with the sCS and nCS conditions. Moreover, the hMT+ was activated equally in both hemispheres in the mCS condition, despite presentation of the cast shadow in the bottom-right quadrant of the stimulus. Perception of the square moving in depth across visual hemifields may be reflected in the bilateral activation of the hMT+. We concluded that the hMT+ is involved in motion perception in depth induced by moving cast shadow and by binocular disparity. PMID:27597999

Electropysiologic evaluation of the visual pathway in patients with multiple sclerosis.

PubMed

Rodriguez-Mena, Diego; Almarcegui, Carmen; Dolz, Isabel; Herrero, Raquel; Bambo, Maria P; Fernandez, Javier; Pablo, Luis E; Garcia-Martin, Elena

2013-08-01

To evaluate the ability of visual evoked potentials and pattern electroretinograms (PERG) to detect subclinical axonal damage in patients during the early diagnostic stage of multiple sclerosis (MS). The authors also compared the ability of optical coherence tomography (OCT), PERG, and visual evoked potentials to detect axonal loss in MS patients and correlated the functional and structural properties of the retinal nerve fiber layer. Two hundred twenty-eight eyes of 114 subjects (57 MS patients and 57 age- and sex-matched healthy controls) were included. The visual pathway was evaluated based on functional and structural assessments. All patients underwent a complete ophthalmic examination that included assessment of visual acuity, ocular motility, intraocular pressure, visual field, papillary morphology, OCT, visual evoked potentials, and PERG. Visual evoked potentials (P100 latency and amplitude), PERG (N95 amplitude and N95/P50 ratio), and OCT parameters differed significantly between MS patients and healthy subjects. Moderate significant correlations were found between visual evoked potentials or PERG parameters and OCT measurements. Axonal damage in ganglion cells of the visual pathway can be detected based on structural measures provided by OCT in MS patients and by the N95 component and N95/P50 index of PERG, thus providing good correlation between function and structure.

Medial Auditory Thalamus Inactivation Prevents Acquisition and Retention of Eyeblink Conditioning

ERIC Educational Resources Information Center

Halverson, Hunter E.; Poremba, Amy; Freeman, John H.

2008-01-01

The auditory conditioned stimulus (CS) pathway that is necessary for delay eyeblink conditioning was investigated using reversible inactivation of the medial auditory thalamic nuclei (MATN) consisting of the medial division of the medial geniculate (MGm), suprageniculate (SG), and posterior intralaminar nucleus (PIN). Rats were given saline or…

Trichoscopy of Steroid-Induced Atrophy.

PubMed

Pirmez, Rodrigo; Abraham, Leonardo S; Duque-Estrada, Bruna; Damasco, Patrícia; Farias, Débora Cadore; Kelly, Yanna; Doche, Isabella

2017-10-01

Intralesional corticosteroid (IL-CS) injections have been used to treat a variety of dermatological and nondermatological diseases. Although an important therapeutic tool in dermatology, a number of local side effects, including skin atrophy, have been reported following IL-CS injections. We recently noticed that a subset of patients with steroid-induced atrophy presented with ivory-colored areas under trichoscopy. We performed a retrospective analysis of trichoscopic images and medical records from patients presenting ivory-colored areas associated with atrophic scalp lesions. In this paper, we associate this feature with the presence of steroid deposits in the dermis and report additional trichoscopic features of steroid-induced atrophy on the scalp, such as prominent blood vessels and visualization of hair bulbs.

Detection of small subendocardial infarction using speckle tracking echocardiography in a rat model.

PubMed

Bachner-Hinenzon, Noa; Shlomo, Liron; Khamis, Hanan; Ertracht, Offir; Vered, Zvi; Malka, Assaf; Binah, Ofer; Adam, Dan

2016-10-01

It is challenging to detect small nontransmural infarcts visually or automatically. As it is important to detect myocardial infarction (MI) at early stages, we tested the hypothesis that small nontransmural MI can be detected using speckle tracking echocardiography (STE) at the acute stage. Minimal nontransmural infarcts were induced in 18 rats by causing recurrent ischemia-reperfusion of the left anterior descending (LAD) coronary artery, followed by a 30-min ligation and by reperfusion. A week later, the scar size was measured by histological analysis. Each rat underwent three echocardiography measurements: at baseline, 1 day post-MI, and 1 week post-MI. To measure the peak circumferential strain (CS), peak systolic CS, radial strain (RS), and time-to-peak (TTP) of the CS, short-axis view of the apex was analyzed by a STE program. The TTP was normalized by the duration of the heart cycle to create percent change of heart cycle. Histological analysis after 1 week showed scar size of 4±6% at the anterior wall. At 24 h post-MI, the peak CS, peak systolic CS, and RS were reduced compared to baseline at the anterior wall due to the MI, and at the adjacent segments-the anterior septum and lateral wall, due to stunning (P<.05). However, only the anterior wall, the genuine damaged segment, showed prolonged TTP vs baseline (baseline 36%, 24 h 48%, P<.05). The TTP of the CS can distinguish between regions adjacent to MI (stunned or tethered) and MI, even in small nontransmural infarcts. © 2016, Wiley Periodicals, Inc.

Characterization and anticancer potential of ferulic acid-loaded chitosan nanoparticles against ME-180 human cervical cancer cell lines

NASA Astrophysics Data System (ADS)

Panwar, Richa; Sharma, Asvene K.; Kaloti, Mandeep; Dutt, Dharm; Pruthi, Vikas

2016-08-01

Ferulic acid (FA) is a widely distributed hydroxycinnamic acid found in various cereals and fruits exhibiting potent antioxidant and anticancer activities. However, due to low solubility and permeability, its availability to biological systems is limited. Non-toxic chitosan-tripolyphosphate pentasodium (CS-TPP) nanoparticles (NPs) are used to load sparingly soluble molecules and drugs, increasing their bioavailability. In the present work, we have encapsulated FA into the CS-TPP NPs to increase its potential as a therapeutic agent. Different concentrations of FA were tested to obtain optimum sized FA-loaded CS-TPP nanoparticles (FA/CS-TPP NPs) by ionic gelation method. Nanoparticles were characterized by scanning electron microscopy, Fourier transformation infrared spectroscopy (FTIR), thermogravimetric analyses and evaluated for their anticancer activity against ME-180 human cervical cancer cell lines. The FTIR spectra confirmed the encapsulation of FA and thermal analysis depicted its degradation profile. A concentration-dependent relationship between FA encapsulation efficiency and FA/CS-TPP NPs diameter was observed. Smooth and spherical FA-loaded cytocompatible nanoparticles with an average diameter of 125 nm were obtained at 40 µM FA conc. The cytotoxicity of 40 µM FA/CS-TPP NPs against ME-180 cervical cancer cell lines was found to be higher as compared to 40 µM native FA. Apoptotic morphological changes as cytoplasmic remnants and damaged wrinkled cells in ME-180 cells were visualized using scanning electron microscopic and fluorescent microscopic techniques. Data concluded that chitosan enveloped FA nanoparticles could be exploited as an excellent therapeutic drug against cancer cells proliferation.

Advanced Visual and Instruction Systems for Maintenance Support (AVIS-MS)

DTIC Science & Technology

2006-12-01

Hayashi , "Augmentable Reality: Situated Communication through Physical and Digital Spaces," Proc. 2nd Int’l Symp. Wearable Computers, IEEE CS Press...H. Ohno , "An Optical See-through Display for Mutual Occlusion of Real and Virtual Environments," Proc. Int’l Symp. Augmented Reality 2000 (ISARO0

A Study of Relationships between Lowenfeld's Perceptual Aptitude Theory and Piaget's Developmental Theory.

ERIC Educational Resources Information Center

Butzow, John W.; Schlenker, Richard M.

1980-01-01

Described is a study which relates Piaget's theory of cognitive development to Lowenfeld's types of perceptual aptitude (i.e., visual v haptic orientation). General interpretations of questionnaire results from university students (N=312) are made that postulate a relationship linking incidence of perceptual and logical ability. (CS)

The Introduction of Crystallographic Concepts Using Lap-Dissolve Slide Techniques.

ERIC Educational Resources Information Center

Bodner, George M.; And Others

1980-01-01

Describes a method using lap-dissolve slide techniques with two or more slide projectors focused on a single screen for presenting visual effects that show structural features in extended arrays of atoms, or ions involving up to several hundred atoms. Presents an outline of an introduction to the structures of crystalline solids. (CS)

The Emergence of Frequency Effects in Eye Movements

ERIC Educational Resources Information Center

Vanyukov, Polina M.; Warren, Tessa; Wheeler, Mark E.; Reichle, Erik D.

2012-01-01

A visual search experiment employed strings of Landolt "C"s to examine how the gap size of and frequency of exposure to distractor strings affected eye movements. Increases in gap size were associated with shorter first-fixation durations, gaze durations, and total times, as well as fewer fixations. Importantly, both the number and duration of…

Learning Computer Science Concepts with Scratch

ERIC Educational Resources Information Center

Meerbaum-Salant, Orni; Armoni, Michal; Ben-Ari, Mordechai

2013-01-01

Scratch is a visual programming environment that is widely used by young people. We investigated if Scratch can be used to teach concepts of computer science (CS). We developed learning materials for middle-school students that were designed according to the constructionist philosophy of Scratch and evaluated them in a few schools during two…

Differences in vision between clinic and home and the effect of lighting in older adults with and without glaucoma

PubMed Central

Bhorade, Anjali M.; Perlmutter, Monica S.; Wilson, Brad; Kambarian, Jamie; Chang, Sidney; Pekmezci, Melike; Gordon, Mae

2015-01-01

Importance Patients often report greater visual difficulties at home than expected from vision testing in the clinic. Such discordance may be due to worse vision in the home than measured in clinic. Objective To compare vision measured between clinic and home and evaluate factors, including lighting, associated with these differences. Design Cross-sectional, between years 2005–2009. Setting Participants recruited from the Glaucoma and Comprehensive Eye Clinics at Washington University, St. Louis, MO underwent a clinic and home visit. Participants 126 glaucoma and 49 non-glaucoma patients, ages 55–90 years, consecutively recruited and met inclusion criteria for this report; 166 eligible patients refused participation. Exposure Participants underwent a clinic and home visit randomized to order of completion. At each visit, masked and certified examiners measured binocular distance visual acuity (DVA) with a non-backlit chart, near visual acuity (NVA), contrast sensitivity (CS), CS with glare, and lighting. Main Outcome Measure Differences in vision between clinic and home. Results Mean scores for all vision tests were significantly better in the clinic than home for glaucoma and non-glaucoma patients (p<0.05, matched pair t-tests). For DVA, 29% of glaucoma participants read ≥2 lines better in clinic than home and 39% with advanced glaucoma read ≥3 lines better. For the entire sample, 21% of participants read ≥2 lines better in clinic than home for NVA and 49% read ≥2 triplets better in clinic for CS with glare. Lighting was the most significant factor associated with differences in vision between clinic and home for DVA, NVA, and CS with glare testing (p<0.05 multiple regression model). Median home lighting was 4.3 times and 2.8 times lower than clinic lighting in areas tested for DVA and NVA, respectively. Home lighting was below that recommended in ≥ 85% of participants. Conclusions and Relevance Vision measured in the clinic is generally better than vision measured at home, with differences mainly due to poor home lighting. Knowledge that vision discrepancies between patient report and clinical testing may be due to home lighting may initiate clinician-patient discussions to increase home lighting and improve vision of older adults in their homes. PMID:24263699

Predicting Cortical Dark/Bright Asymmetries from Natural Image Statistics and Early Visual Transforms

PubMed Central

Cooper, Emily A.; Norcia, Anthony M.

2015-01-01

The nervous system has evolved in an environment with structure and predictability. One of the ubiquitous principles of sensory systems is the creation of circuits that capitalize on this predictability. Previous work has identified predictable non-uniformities in the distributions of basic visual features in natural images that are relevant to the encoding tasks of the visual system. Here, we report that the well-established statistical distributions of visual features -- such as visual contrast, spatial scale, and depth -- differ between bright and dark image components. Following this analysis, we go on to trace how these differences in natural images translate into different patterns of cortical input that arise from the separate bright (ON) and dark (OFF) pathways originating in the retina. We use models of these early visual pathways to transform natural images into statistical patterns of cortical input. The models include the receptive fields and non-linear response properties of the magnocellular (M) and parvocellular (P) pathways, with their ON and OFF pathway divisions. The results indicate that there are regularities in visual cortical input beyond those that have previously been appreciated from the direct analysis of natural images. In particular, several dark/bright asymmetries provide a potential account for recently discovered asymmetries in how the brain processes visual features, such as violations of classic energy-type models. On the basis of our analysis, we expect that the dark/bright dichotomy in natural images plays a key role in the generation of both cortical and perceptual asymmetries. PMID:26020624

Pathview Web: user friendly pathway visualization and data integration

PubMed Central

Pant, Gaurav; Bhavnasi, Yeshvant K.; Blanchard, Steven G.; Brouwer, Cory

2017-01-01

Abstract Pathway analysis is widely used in omics studies. Pathway-based data integration and visualization is a critical component of the analysis. To address this need, we recently developed a novel R package called Pathview. Pathview maps, integrates and renders a large variety of biological data onto molecular pathway graphs. Here we developed the Pathview Web server, as to make pathway visualization and data integration accessible to all scientists, including those without the special computing skills or resources. Pathview Web features an intuitive graphical web interface and a user centered design. The server not only expands the core functions of Pathview, but also provides many useful features not available in the offline R package. Importantly, the server presents a comprehensive workflow for both regular and integrated pathway analysis of multiple omics data. In addition, the server also provides a RESTful API for programmatic access and conveniently integration in third-party software or workflows. Pathview Web is openly and freely accessible at https://pathview.uncc.edu/. PMID:28482075

The Role of Lamination in Neocortical Function

DTIC Science & Technology

1991-12-20

U. Studies of the Tectofugal System: Tectal pathways to the telencephalon in birds and mammals. The tecto-thalamo-telencephalic visual pathway is...significance of lamination of the telencephalon . Visual Structures and Integrated Functions, Research Notes in Neural Computing (Michael Arbib and J6rg

Anatomical evidence for the influence of degenerating pathways on regenerating optic fibers following surgical manipulations in the visual system of the goldfish.

PubMed

Lo, R Y; Levine, R L

1981-04-06

We have used [3H]proline radioautography to trace regenerating optic fibers in the goldfish following: (1) the removal of the right tectal lobe and the right eye, and (2) the removal of both tectal lobes. Our results indicate that following the removal of the right tectal lobe and the right eye, both the denervated tectal efferent pathways, and the denervated visual pathways and terminal zones of the enucleated eye were penetrated by the regenerating optic fibers. In addition, following bilateral lobectomy, the denervated tectal efferent pathways were bilaterally penetrated by the regenerating fibers. Since, in both types of operations, these denervated pathways and terminal zones should undergo degeneration, our results support the suggestion that the presence of degenerating axonal debris and proliferating glia may play an important role in guiding regenerating optic fibers in the visual system of the goldfish.

Processes, dynamics and modelling of radiocaesium cycling in a chronosequence of Chernobyl-contaminated Scots pine (Pinus sylvestris L.) plantations.

PubMed

Goor, François; Thiry, Yves

2004-06-05

In a large forested area affected by the Chernobyl radioactive fallout, especially in CIS, the lasting recycling of radiocaesium (137Cs) by the trees is a source of long-term contamination of woody products. The quantitative description of the 137Cs dynamics in contaminated forest is a prerequisite to predictive modelling and further management of such territories. Three even-aged mono-specific Scots pine stands (17, 37 and 57 years old) were selected in a contaminated woodland in southeastern Belarus to constitute an adequate chronosequence. We determined the potassium and radiocaesium annual fluxes involved in the biological cycling in each stand using a well-documented calculation methodology. Qualitatively, 137Cs was shown to be rapidly recycled in trees through the same pathways as K and to redistribute similarly between the tree components. Compared to K, a higher fraction of 137Cs, corresponding to about the half of the annual uptake, is immobilised in perennial organs. With tree development, trunk wood and bark become prevailing sinks for 137Cs since they represent an increasing pool of biomass. In the pine chronosequence, the current root absorption, respectively, mobilizes 0.53, 0.32 and 0.31% year(-1) of the total 137Cs pool in soil. Variations in the 137Cs uptake do not reflect differences in the 137Cs balance between stands. In the two older stands, 51 and 71% of the current tree contamination are related to earlier accumulation subsequent to the initial fallout interception and recycling. The soil is the dominant source of long-term tree contamination. A simple modelling based on the measured 137Cs fluxes indicates that, for young stands, radioactive decay-corrected contamination would stabilize after reaching a maximum of 25 years after the 137Cs deposition. Stemwood presents a maximum of 15 years after the deposition and decrease afterwards mainly through radioactive decay. In the older stands, the decontamination is constant without local maximum of 137Cs level in the wood. The 137Cs contamination of tree components is the result of different influential processes like root uptake, internal translocation and immobilisation. For more accurate predictions, the calibration of existing models would be benefited by comparing with the 137Cs annual fluxes instead of the simple transfer factor coefficients. In the perspective of other applications, there is a need of such data for other radionuclides as well as for heavy metals. Copryright 2003 Elsevier B.V.

MTOR Suppresses Cigarette Smoke-Induced Epithelial Cell Death and Airway Inflammation in Chronic Obstructive Pulmonary Disease.

PubMed

Wang, Yong; Liu, Juan; Zhou, Jie-Sen; Huang, Hua-Qiong; Li, Zhou-Yang; Xu, Xu-Chen; Lai, Tian-Wen; Hu, Yue; Zhou, Hong-Bin; Chen, Hai-Pin; Ying, Song-Min; Li, Wen; Shen, Hua-Hao; Chen, Zhi-Hua

2018-04-15

Airway epithelial cell death and inflammation are pathological features of chronic obstructive pulmonary disease (COPD). Mechanistic target of rapamycin (MTOR) is involved in inflammation and multiple cellular processes, e.g., autophagy and apoptosis, but little is known about its function in COPD pathogenesis. In this article, we illustrate how MTOR regulates cigarette smoke (CS)-induced cell death, airway inflammation, and emphysema. Expression of MTOR was significantly decreased and its suppressive signaling protein, tuberous sclerosis 2 (TSC2), was increased in the airway epithelium of human COPD and in mouse lungs with chronic CS exposure. In human bronchial epithelial cells, CS extract (CSE) activated TSC2, inhibited MTOR, and induced autophagy. The TSC2-MTOR axis orchestrated CSE-induced autophagy, apoptosis, and necroptosis in human bronchial epithelial cells; all of which cooperatively regulated CSE-induced inflammatory cytokines IL-6 and IL-8 through the NF-κB pathway. Mice with a specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly augmented airway inflammation and airspace enlargement in response to CS exposure, accompanied with enhanced levels of autophagy, apoptosis, and necroptosis in the lungs. Taken together, these data demonstrate that MTOR suppresses CS-induced inflammation and emphysema-likely through modulation of autophagy, apoptosis, and necroptosis-and thus suggest that activation of MTOR may represent a novel therapeutic strategy for COPD. Copyright © 2018 by The American Association of Immunologists, Inc.

Molecular cloning and characterisation of a pathogenesis-related protein CsPR10 from Crocus sativus.

PubMed

Gómez-Gómez, L; Rubio-Moraga, A; Ahrazem, O

2011-03-01

Plants have developed many mechanisms to protect themselves against most potential microbial pathogens and diseases. Among these mechanisms, pathogenesis-related proteins are produced as part of the active defence to prevent attack. In this study, a full-length cDNA encoding the CsPR10 protein was identified in fresh saffron stigmas (Crocus sativus). The deduced amino acid sequence from the nucleotide sequence of the coding region showed homology with PR10 proteins. The clone expressed as a protein in fusion with a GST tag produced a 47-kDa protein in E. coli. CsPR10 had ribonuclease activity, with features common to class II-type ribonucleases; its specific activity was quantified as 68.8 U·mg(-1) protein, thus falling within the range of most PR10 proteins exhibiting RNase activity. Antifungal activity of CsPR10 was assayed against Verticillium dahliae, Penicillium sp. and Fusarium oxysporum. CsPR10 inhibited only F. oxysporum growth, and antifungal potency was reflected in a IC(50) of 8.3 μm. Expression analysis showed the presence of high transcript levels in anther and tepal tissues, low levels in stigmas and roots, and no signal detected in leaves. This protein seems to be involved in the active defence response through activation of the jasmonic acid pathway. © 2010 German Botanical Society and The Royal Botanical Society of the Netherlands.

Circadian activity rhythms during the last days of Nothobranchius rachovii's life: a descriptive model of circadian system breakdown.

PubMed

Lucas-Sánchez, Alejandro; Martínez-Nicolás, Antonio; Madrid, Juan Antonio; Almaida-Pagán, Pedro Francisco; Mendiola, Pilar; de Costa, Jorge

2015-04-01

Several studies have been performed to identify age-related changes in the circadian system (CS) but the impairment of the CS and its chronodisruption at the end of an organism life have not been studied in depth. Aging commonly affects the input pathways into the biological clock or restraints their processing, therefore simplifying the system output, the overt rhythms. The purpose of this work was to do a complete characterization of changes that occurs in the CS in the last stage of a vertebrate organism life and to develop tools able to detect in which moment of the last days of life is the animal, using an overt rhythm, the rest-activity rhythm (RAR). For that, a fish species proposed as model for aging studies, Nothobranchius rachovii, has been used. A progressive and sequential CS breakdown has been described for the last 22 d of life of N. rachovii (∼7% of total life), suffering a general RAR impairment mainly reflected by changes in phase regularity, complexity, amplitude and the ability to stay synchronized to the LD cycle. Also, an equation of days remaining of life, based on the RAR description, has been calculated and proposed as a tool to identify close-to-death individuals which could be subjected to an adequate restoring treatment to enhance the CS function and improve their well-being.

Synthesis of Fucosylated Chondroitin Sulfate Glycoclusters: A Robust Route to New Anticoagulant Agents.

PubMed

Zhang, Xiao; Yao, Wang; Xu, Xiaojiang; Sun, Huifang; Zhao, Jinhua; Meng, Xiangbao; Wu, Mingyi; Li, Zhongjun

2018-02-01

Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan with excellent anticoagulant activity. Studies show that FuCS and its depolymerized fragments exhibit a different anticoagulant mechanism from that of heparin derivatives, with decreased risks of adverse effects and bleeding. However, further exploitation has been hindered by the scarcity of structurally defined oligosaccharides. Herein, facile method is reported for the synthesis of the repeating trisaccharide unit of FuCS based on the degradation of chondroitin sulfate polymers. A series of simplified FuCS glycomimetics that have highly tunable structures, controllable branches, and defined sulfation motifs were generated by copper-catalyzed alkyne-azide cycloaddition. Remarkable improvement in activated partial thromboplastin time (APTT) assay activities was observed as the branches increased, but no significant influences were observed for prothrombin time (PT) and thrombin time (TT) assay activities. Further FXase inhibition tests suggested that glycoclusters 33 b-40 b selectively inhibited intrinsic anticoagulant activities, but had little effect on the extrinsic and common coagulation pathways. Notably, glycoclusters with the 2,4-di-O-sulfated fucosyl residue displayed the most potency, which was in consistent with that of natural polysaccharides. These FuCS clusters demonstrated potency to mimic linear glycosaminoglycans and offer a new framework for the development of novel anticoagulant agents. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Novel Aerobic Degradation Pathway for Thiobencarb Is Initiated by the TmoAB Two-Component Flavin Mononucleotide-Dependent Monooxygenase System in Acidovorax sp. Strain T1.

PubMed

Chu, Cui-Wei; Liu, Bin; Li, Na; Yao, Shi-Gang; Cheng, Dan; Zhao, Jia-Dong; Qiu, Ji-Guo; Yan, Xin; He, Qin; He, Jian

2017-12-01

Thiobencarb is a thiocarbamate herbicide used in rice paddies worldwide. Microbial degradation plays a crucial role in the dissipation of thiobencarb in the environment. However, the physiological and genetic mechanisms underlying thiobencarb degradation remain unknown. In this study, a novel thiobencarb degradation pathway was proposed in Acidovorax sp. strain T1. Thiobencarb was oxidized and cleaved at the C-S bond, generating diethylcarbamothioic S -acid and 4-chlorobenzaldehyde (4CDA). 4CDA was then oxidized to 4-chlorobenzoic acid (4CBA) and hydrolytically dechlorinated to 4-hydroxybenzoic acid (4HBA). The identification of catabolic genes suggested further hydroxylation to protocatechuic acid (PCA) and finally degradation through the protocatechuate 4,5-dioxygenase pathway. A novel two-component monooxygenase system identified in the strain, TmoAB, was responsible for the initial catabolic reaction. TmoA shared 28 to 32% identity with the oxygenase components of pyrimidine monooxygenase from Agrobacterium fabrum , alkanesulfonate monooxygenase from Pseudomonas savastanoi , and dibenzothiophene monooxygenase from Rhodococcus sp. TmoB shared 25 to 37% identity with reported flavin reductases and oxidized NADH but not NADPH. TmoAB is a flavin mononucleotide (FMN)-dependent monooxygenase and catalyzed the C-S bond cleavage of thiobencarb. Introduction of tmoAB into cells of the thiobencarb degradation-deficient mutant T1m restored its ability to degrade and utilize thiobencarb. A dehydrogenase gene, tmoC , was located 7,129 bp downstream of tmoAB , and its transcription was clearly induced by thiobencarb. The purified TmoC catalyzed the dehydrogenation of 4CDA to 4CBA using NAD + as a cofactor. A gene cluster responsible for the complete 4CBA metabolic pathway was also cloned, and its involvement in thiobencarb degradation was preliminarily verified by transcriptional analysis. IMPORTANCE Microbial degradation is the main factor in thiobencarb dissipation in soil. In previous studies, thiobencarb was degraded initially via N -deethylation, sulfoxidation, hydroxylation, and dechlorination. However, enzymes and genes involved in the microbial degradation of thiobencarb have not been studied. This study revealed a new thiobencarb degradation pathway in Acidovorax sp. strain T1 and identified a novel two-component FMN-dependent monooxygenase system, TmoAB. Under TmoAB-mediated catalysis, thiobencarb was cleaved at the C-S bond, producing diethylcarbamothioic S -acid and 4CDA. Furthermore, the downstream degradation pathway of thiobencarb was proposed. Our study provides the physiological, biochemical, and genetic foundation of thiobencarb degradation in this microorganism. Copyright © 2017 American Society for Microbiology.

Improving isotopic identification with INDRA Silicon-CsI(Tl) telescopes

NASA Astrophysics Data System (ADS)

Lopez, O.; Pârlog, M.; Borderie, B.; Rivet, M. F.; Lehaut, G.; Tabacaru, G.; Tassan-Got, L.; Pawłowski, P.; Bonnet, E.; Bougault, R.; Chbihi, A.; Dell'Aquila, D.; Frankland, J. D.; Galichet, E.; Gruyer, D.; La Commara, M.; Le Neindre, N.; Lombardo, I.; Manduci, L.; Marini, P.; Steckmeyer, J. C.; Verde, G.; Vient, E.; Wieleczko, J. P.; Indra Collaboration

2018-03-01

Profiting from previous works done with the INDRA multidetector on the description of the light response L of the CsI(Tl) crystals to different impinging nuclei, we propose an improved ΔE - L identification-calibration procedure for Silicon-Caesium Iodide (Si-CsI) telescopes, namely an Advanced Mass Estimate (AME) method. AME is compared to the usual, simple visual analysis of the corresponding two-dimensional map of ΔE - E type, by using INDRA experimental data from nuclear reactions induced by heavy ions in the Fermi energy regime. We show that the capability of such telescopes to identify both the atomic Z and the mass A numbers of light and heavy reaction products, can be quantitatively improved thanks to the proposed approach. This conclusion opens new possibilities to use INDRA for studying these reactions especially with radioactive beams. Indeed, the determination of the mass for charged reaction products becomes of paramount importance to shed light on the role of the isospin degree of freedom in the nuclear equation of state [1,2].

Optical scanning holography based on compressive sensing using a digital micro-mirror device

NASA Astrophysics Data System (ADS)

A-qian, Sun; Ding-fu, Zhou; Sheng, Yuan; You-jun, Hu; Peng, Zhang; Jian-ming, Yue; xin, Zhou

2017-02-01

Optical scanning holography (OSH) is a distinct digital holography technique, which uses a single two-dimensional (2D) scanning process to record the hologram of a three-dimensional (3D) object. Usually, these 2D scanning processes are in the form of mechanical scanning, and the quality of recorded hologram may be affected due to the limitation of mechanical scanning accuracy and unavoidable vibration of stepper motor's start-stop. In this paper, we propose a new framework, which replaces the 2D mechanical scanning mirrors with a Digital Micro-mirror Device (DMD) to modulate the scanning light field, and we call it OSH based on Compressive Sensing (CS) using a digital micro-mirror device (CS-OSH). CS-OSH can reconstruct the hologram of an object through the use of compressive sensing theory, and then restore the image of object itself. Numerical simulation results confirm this new type OSH can get a reconstructed image with favorable visual quality even under the condition of a low sample rate.

Elaborate mapping of the posterior visual pathway in awake craniotomy.

PubMed

Shahar, Tal; Korn, Akiva; Barkay, Gal; Biron, Tali; Hadanny, Amir; Gazit, Tomer; Nossek, Erez; Ekstein, Margaret; Kesler, Anat; Ram, Zvi

2018-05-01

OBJECTIVE Resection of intraaxial tumors adjacent to the optic radiation (OR) may be associated with postoperative visual field (VF) deficits. Intraoperative navigation using MRI-based tractography and electrophysiological monitoring of the visual pathways may allow maximal resection while preserving visual function. In this study, the authors evaluated the value of visual pathway mapping in a series of patients undergoing awake craniotomy for tumor resection. METHODS A retrospective analysis of prospectively collected data was conducted in 18 patients who underwent an awake craniotomy for resection of intraaxial tumors involving or adjacent to the OR. Preoperative MRI-based tractography was used for intraoperative navigation, and intraoperative acquisition of 3D ultrasonography images was performed for real-time imaging and correction of brain shift. Goggles with light-emitting diodes were used as a standard visual stimulus. Direct cortical visual evoked potential (VEP) recording, subcortical recordings from the OR, and subcortical stimulation of the OR were used intraoperatively to assess visual function and proximity of the lesion to the OR. VFs were assessed pre- and postoperatively. RESULTS Baseline cortical VEP recordings were available for 14 patients (77.7%). No association was found between preoperative VF status and baseline presence of cortical VEPs (p = 0.27). Five of the 14 patients (35.7%) who underwent subcortical stimulation of the OR reported seeing phosphenes in the corresponding contralateral VF. There was a positive correlation (r = 0.899, p = 0.04) between the subcortical threshold stimulation intensity (3-11.5 mA) and the distance from the OR. Subcortical recordings from the OR demonstrated a typical VEP waveform in 10 of the 13 evaluated patients (76.9%). These waveforms were present only when recordings were obtained within 10 mm of the OR (p = 0.04). Seven patients (38.9%) had postoperative VF deterioration, and it was associated with a length of < 8 mm between the tumor and the OR (p = 0.05). CONCLUSIONS Intraoperative electrophysiological monitoring of the visual pathways is feasible but may be of limited value in preserving the functional integrity of the posterior visual pathways. Subcortical stimulation of the OR may identify the location of the OR when done in proximity to the pathways, but such proximity may be associated with increased risk of postoperative worsening of the VF deficit.

Effective Half-Life of Caesium-137 in Various Environmental Media at the Savannah River Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paller, M. H.; Jannik, G. T.; Baker, R. A.

2014-05-01

During the operational history of the Savannah River Site (SRS), many different radionuclides have been released from site facilities into the SRS environment. However, only a relatively small number of pathways, most importantly 137Cs in fish and deer, have contributed significantly to doses and risks to the public. The “effective” half-lives (T e) of 137Cs (which include both physical decay and environmental dispersion) in Savannah River floodplain soil and vegetation and in fish and white-tailed deer from the SRS were estimated using long-term monitoring data. For 1974–2011, the T es of 137Cs in Savannah River floodplain soil and vegetation weremore » 17.0 years (95% CI = 14.2–19.9) and 13.4 years (95% CI = 10.8–16.0), respectively. These T es were greater than in a previous study that used data collected only through 2005 as a likely result of changes in the flood regime of the Savannah River. Field analyses of 137Cs concentrations in deer collected during yearly controlled hunts at the SRS indicated an overall T e of 15.9 years (95% CI = 12.3–19.6) for 1965–2011; however, the T e for 1990–2011 was significantly shorter (11.8 years, 95% CI = 4.8–18.8) due to an increase in the rate of 137Cs removal. The shortest T es were for fish in SRS streams and the Savannah River (3.5–9.0 years), where dilution and dispersal resulted in rapid 137Cs removal. Long-term data show that T es are significantly shorter than the physical half-life of 137Cs in the SRS environment but that they can change over time. Therefore, it is desirable have a long period of record for calculating Tes and risky to extrapolate T es beyond this period unless the processes governing 137Cs removal are clearly understood.« less

Molecular Cloning and Characterization of Taurocyamine Kinase from Clonorchis sinensis: A Candidate Chemotherapeutic Target

PubMed Central

Tokuhiro, Shinji; Nagataki, Mitsuru; Jarilla, Blanca R.; Nomura, Haruka; Kim, Tae Im; Hong, Sung-Jong; Agatsuma, Takeshi

2013-01-01

Background Adult Clonorchis sinensis lives in the bile duct and causes endemic clonorchiasis in East Asian countries. Phosphagen kinases (PK) constitute a highly conserved family of enzymes, which play a role in ATP buffering in cells, and are potential targets for chemotherapeutic agents, since variants of PK are found only in invertebrate animals, including helminthic parasites. This work is conducted to characterize a PK from C. sinensis and to address further investigation for future drug development. Methology/Principal findings A cDNA clone encoding a putative polypeptide of 717 amino acids was retrieved from a C. sinensis transcriptome. This polypeptide was homologous to taurocyamine kinase (TK) of the invertebrate animals and consisted of two contiguous domains. C. sinensis TK (CsTK) gene was reported and found consist of 13 exons intercalated with 12 introns. This suggested an evolutionary pathway originating from an arginine kinase gene group, and distinguished annelid TK from the general CK phylogenetic group. CsTK was found not to have a homologous counterpart in sequences analysis of its mammalian hosts from public databases. Individual domains of CsTK, as well as the whole two-domain enzyme, showed enzymatic activity and specificity toward taurocyamine substrate. Of the CsTK residues, R58, I60 and Y84 of domain 1, and H60, I63 and Y87 of domain 2 were found to participate in binding taurocyamine. CsTK expression was distributed in locomotive and reproductive organs of adult C. sinensis. Developmentally, CsTK was stably expressed in both the adult and metacercariae stages. Recombinant CsTK protein was found to have low sensitivity and specificity toward C. sinensis and platyhelminth-infected human sera on ELISA. Conclusion CsTK is a promising anti-C. sinensis drug target since the enzyme is found only in the C. sinensis and has a substrate specificity for taurocyamine, which is different from its mammalian counterpart, creatine. PMID:24278491

Apical dominance in saffron and the involvement of the branching enzymes CCD7 and CCD8 in the control of bud sprouting

PubMed Central

2014-01-01

Background In saffron (Crocus sativus), new corms develop at the base of every shoot developed from the maternal corm, a globular underground storage stem. Since the degree of bud sprouts influences the number and size of new corms, and strigolactones (SLs) suppress growth of pre-formed axillary bud, it was considered appropriate to investigate SL involvement in physiology and molecular biology in saffron. We focused on two of the genes within the SL pathway, CCD7 and CCD8, encoding carotenoid cleavage enzymes required for the production of SLs. Results The CsCCD7 and CsCCD8 genes are the first ones isolated and characterized from a non-grass monocotyledonous plant. CsCCD7 and CsCCD8 expression showed some overlapping, although they were not identical. CsCCD8 was highly expressed in quiescent axillary buds and decapitation dramatically reduced its expression levels, suggesting its involvement in the suppression of axillary bud outgrowth. Furthermore, in vitro experiments showed also the involvement of auxin, cytokinin and jasmonic acid on the sprouting of axillary buds from corms in which the apical bud was removed. In addition, CsCCD8 expression, but not CsCCD7, was higher in the newly developed vascular tissue of axillary buds compared to the vascular tissue of the apical bud. Conclusions We showed that production and transport of auxin in saffron corms could act synergistically with SLs to arrest the outgrowth of the axillary buds, similar to the control of above-ground shoot branching. In addition, jasmonic acid seems to play a prominent role in bud dormancy in saffron. While cytokinins from roots promote bud outgrowth. In addition the expression results of CsCCD8 suggest that SLs could positively regulate procambial activity and the development of new vascular tissues connecting leaves with the mother corm. PMID:24947472

A new neural framework for visuospatial processing

PubMed Central

Kravitz, Dwight J.; Saleem, Kadharbatcha S.; Baker, Chris I.; Mishkin, Mortimer

2012-01-01

The division of cortical visual processing into distinct dorsal and ventral streams is a key framework that has guided visual neuroscience. The characterization of the ventral stream as a ‘What’ pathway is relatively uncontroversial, but the nature of dorsal stream processing is less clear. Originally proposed as mediating spatial perception (‘Where’), more recent accounts suggest it primarily serves non-conscious visually guided action (‘How’). Here, we identify three pathways emerging from the dorsal stream that consist of projections to the prefrontal and premotor cortices, and a major projection to the medial temporal lobe that courses both directly and indirectly through the posterior cingulate and retrosplenial cortices. These three pathways support both conscious and non-conscious visuospatial processing, including spatial working memory, visually guided action and navigation, respectively. PMID:21415848

Dissociation and Convergence of the Dorsal and Ventral Visual Streams in the Human Prefrontal Cortex

PubMed Central

Takahashi, Emi; Ohki, Kenichi; Kim, Dae-Shik

2012-01-01

Visual information is largely processed through two pathways in the primate brain: an object pathway from the primary visual cortex to the temporal cortex (ventral stream) and a spatial pathway to the parietal cortex (dorsal stream). Whether and to what extent dissociation exists in the human prefrontal cortex (PFC) has long been debated. We examined anatomical connections from functionally defined areas in the temporal and parietal cortices to the PFC, using noninvasive functional and diffusion-weighted magnetic resonance imaging. The right inferior frontal gyrus (IFG) received converging input from both streams, while the right superior frontal gyrus received input only from the dorsal stream. Interstream functional connectivity to the IFG was dynamically recruited only when both object and spatial information were processed. These results suggest that the human PFC receives dissociated and converging visual pathways, and that the right IFG region serves as an integrator of the two types of information. PMID:23063444

Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain.

PubMed

Hanafy, Amira S; Farid, Ragwa M; ElGamal, Safaa S

2015-01-01

Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing. Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully delivered to different brain regions shortly after intranasal administration suggesting their potential as a delivery system for Alzheimer's disease management.

Encodings of implied motion for animate and inanimate object categories in the two visual pathways.

PubMed

Lu, Zhengang; Li, Xueting; Meng, Ming

2016-01-15

Previous research has proposed two separate pathways for visual processing: the dorsal pathway for "where" information vs. the ventral pathway for "what" information. Interestingly, the middle temporal cortex (MT) in the dorsal pathway is involved in representing implied motion from still pictures, suggesting an interaction between motion and object related processing. However, the relationship between how the brain encodes implied motion and how the brain encodes object/scene categories is unclear. To address this question, fMRI was used to measure activity along the two pathways corresponding to different animate and inanimate categories of still pictures with different levels of implied motion speed. In the visual areas of both pathways, activity induced by pictures of humans and animals was hardly modulated by the implied motion speed. By contrast, activity in these areas correlated with the implied motion speed for pictures of inanimate objects and scenes. The interaction between implied motion speed and stimuli category was significant, suggesting different encoding mechanisms of implied motion for animate-inanimate distinction. Further multivariate pattern analysis of activity in the dorsal pathway revealed significant effects of stimulus category that are comparable to the ventral pathway. Moreover, still pictures of inanimate objects/scenes with higher implied motion speed evoked activation patterns that were difficult to differentiate from those evoked by pictures of humans and animals, indicating a functional role of implied motion in the representation of object categories. These results provide novel evidence to support integrated encoding of motion and object categories, suggesting a rethink of the relationship between the two visual pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Designing a Care Pathway Model - A Case Study of the Outpatient Total Hip Arthroplasty Care Pathway.

PubMed

Oosterholt, Robin I; Simonse, Lianne Wl; Boess, Stella U; Vehmeijer, Stephan Bw

2017-03-09

Although the clinical attributes of total hip arthroplasty (THA) care pathways have been thoroughly researched, a detailed understanding of the equally important organisational attributes is still lacking. The aim of this article is to contribute with a model of the outpatient THA care pathway that depicts how the care team should be organised to enable patient discharge on the day of surgery. The outpatient THA care pathway enables patients to be discharged on the day of surgery, shortening the length of stay and intensifying the provision and organisation of care. We utilise visual care modelling to construct a visual design of the organisation of the care pathway. An embedded case study was conducted of the outpatient THA care pathway at a teaching hospital in the Netherlands. The data were collected using a visual care modelling toolkit in 16 semi-structured interviews. Problems and inefficiencies in the care pathway were identified and addressed in the iterative design process. The results are two visual models of the most critical phases of the outpatient THA care pathway: diagnosis & preparation (1) and mobilisation & discharge (4). The results show the care team composition, critical value exchanges, and sequence that enable patient discharge on the day of surgery. The design addressed existing problems and is an optimisation of the case hospital's pathway. The network of actors consists of the patient (1), radiologist (1), anaesthetist (1), nurse specialist (1), pharmacist (1), orthopaedic surgeon (1,4), physiotherapist (1,4), nurse (4), doctor (4) and patient application (1,4). The critical value exchanges include patient preparation (mental and practical), patient education, aligned care team, efficient sequence of value exchanges, early patient mobilisation, flexible availability of the physiotherapist, functional discharge criteria, joint decision making and availability of the care team.

Smoke-induced microRNA and related proteome alterations. Modulation by chemopreventive agents.

PubMed

De Flora, Silvio; Balansky, Roumen; D'Agostini, Francesco; Cartiglia, Cristina; Longobardi, Mariagrazia; Steele, Vernon E; Izzotti, Alberto

2012-12-15

Dysregulation of microRNAs (miRNAs) has important consequences on gene and protein expression since a single miRNA targets a number of genes simultaneously. This article provides a review of published data and ongoing studies regarding the effects of cigarette smoke (CS), either mainstream (MCS) or environmental (ECS), on the expression of miRNAs and related proteins. The results generated in mice, rats, and humans provided evidence that exposure to CS results in an intense dysregulation of miRNA expression in the respiratory tract, which is mainly oriented in the sense of downregulation. In parallel, there was an upregulation of proteins targeted by the downregulated miRNAs. These trends reflect an attempt to defend the respiratory tract by means of antioxidant mechanisms, detoxification of carcinogens, DNA repair, anti-inflammatory pathways, apoptosis, etc. However, a long-lasting exposure to CS causes irreversible miRNA alterations that activate carcinogenic mechanisms, such as modulation of oncogenes and oncosuppressor genes, cell proliferation, recruitment of undifferentiated stem cells, inflammation, inhibition of intercellular communications, angiogenesis, invasion, and metastasis. The miRNA alterations induced by CS in the lung of mice and rats are similar to those observed in the human respiratory tract. Since a number of miRNAs that are modulated by CS and/or chemopreventive agents are subjected to single nucleotide polymorphisms in humans, they can be evaluated according to toxicogenomic/pharmacogenomics approaches. A variety of cancer chemopreventive agents tested in our laboratory modulated both baseline and CS-related miRNA and proteome alterations, thus contributing to evaluate both safety and efficacy of dietary and pharmacological agents. Copyright © 2012 UICC.

Generalization of Pain-Related Fear Based on Conceptual Knowledge.

PubMed

Meulders, Ann; Vandael, Kristof; Vlaeyen, Johan W S

2017-05-01

Increasing evidence suggests that pain-related fear is key to the transition from acute to chronic pain. Previous research has shown that perceptual similarity with a pain-associated movement fosters the generalization of fear to novel movements. Perceptual generalization of pain-related fear is adaptive as it enables individuals to extrapolate the threat value of one movement to another without the necessity to learn anew. However, excessive spreading of fear to safe movements may become maladaptive and may lead to sustained anxiety, dysfunctional avoidance behaviors, and severe disability. A hallmark of human cognition is the ability to extract conceptual knowledge from a learning episode as well. Although this conceptual pathway may be important to understand fear generalization in chronic pain, research on this topic is lacking. We investigated acquisition and generalization of concept-based pain-related fear. During acquisition, unique exemplars of one action category (CS+; e.g., opening boxes) were followed by pain, whereas exemplars of another action category (CS-; e.g., closing boxes) were not. Subsequently, spreading of pain-related fear to novel exemplars of both action categories was tested. Participants learned to expect the pain to occur and reported more pain-related fear to the exemplars of the CS+ category compared with those of the CS- category. During generalization, fear and expectancy generalized to novel exemplars of the CS+ category, but not to the CS- category. This pattern was not corroborated in the eyeblink startle measures. This is the first study that demonstrates that pain-related fear can be acquired and generalized based on conceptual knowledge. Copyright © 2016. Published by Elsevier Ltd.

Genetic parameter estimates for carcass traits and visual scores including or not genomic information.

PubMed

Gordo, D G M; Espigolan, R; Tonussi, R L; Júnior, G A F; Bresolin, T; Magalhães, A F Braga; Feitosa, F L; Baldi, F; Carvalheiro, R; Tonhati, H; de Oliveira, H N; Chardulo, L A L; de Albuquerque, L G

2016-05-01

The objective of this study was to determine whether visual scores used as selection criteria in Nellore breeding programs are effective indicators of carcass traits measured after slaughter. Additionally, this study evaluated the effect of different structures of the relationship matrix ( and ) on the estimation of genetic parameters and on the prediction accuracy of breeding values. There were 13,524 animals for visual scores of conformation (CS), finishing precocity (FP), and muscling (MS) and 1,753, 1,747, and 1,564 for LM area (LMA), backfat thickness (BF), and HCW, respectively. Of these, 1,566 animals were genotyped using a high-density panel containing 777,962 SNP. Six analyses were performed using multitrait animal models, each including the 3 visual scores and 1 carcass trait. For the visual scores, the model included direct additive genetic and residual random effects and the fixed effects of contemporary group (defined by year of birth, management group at yearling, and farm) and the linear effect of age of animal at yearling. The same model was used for the carcass traits, replacing the effect of age of animal at yearling with the linear effect of age of animal at slaughter. The variance and covariance components were estimated by the REML method in analyses using the numerator relationship matrix () or combining the genomic and the numerator relationship matrices (). The heritability estimates for the visual scores obtained with the 2 methods were similar and of moderate magnitude (0.23-0.34), indicating that these traits should response to direct selection. The heritabilities for LMA, BF, and HCW were 0.13, 0.07, and 0.17, respectively, using matrix and 0.29, 0.16, and 0.23, respectively, using matrix . The genetic correlations between the visual scores and carcass traits were positive, and higher correlations were generally obtained when matrix was used. Considering the difficulties and cost of measuring carcass traits postmortem, visual scores of CS, FP, and MS could be used as selection criteria to improve HCW, BF, and LMA. The use of genomic information permitted the detection of greater additive genetic variability for LMA and BF. For HCW, the high magnitude of the genetic correlations with visual scores was probably sufficient to recover genetic variability. The methods provided similar breeding value accuracies, especially for the visual scores.

Improvement of uncorrected visual acuity and contrast sensitivity with perceptual learning and transcranial random noise stimulation in individuals with mild myopia

PubMed Central

Camilleri, Rebecca; Pavan, Andrea; Ghin, Filippo; Battaglini, Luca; Campana, Gianluca

2014-01-01

Perceptual learning has been shown to produce an improvement of visual acuity (VA) and contrast sensitivity (CS) both in subjects with amblyopia and refractive defects such as myopia or presbyopia. Transcranial random noise stimulation (tRNS) has proven to be efficacious in accelerating neural plasticity and boosting perceptual learning in healthy participants. In this study, we investigated whether a short behavioral training regime using a contrast detection task combined with online tRNS was as effective in improving visual functions in participants with mild myopia compared to a 2-month behavioral training regime without tRNS (Camilleri et al., 2014). After 2 weeks of perceptual training in combination with tRNS, participants showed an improvement of 0.15 LogMAR in uncorrected VA (UCVA) that was comparable with that obtained after 8 weeks of training with no tRNS, and an improvement in uncorrected CS (UCCS) at various spatial frequencies (whereas no UCCS improvement was seen after 8 weeks of training with no tRNS). On the other hand, a control group that trained for 2 weeks without stimulation did not show any significant UCVA or UCCS improvement. These results suggest that the combination of behavioral and neuromodulatory techniques can be fast and efficacious in improving sight in individuals with mild myopia. PMID:25400610

[Case with probable dementia with Lewy bodies, who shows reduplicative paramnesia and Capgras syndrome].

PubMed

Ohara, Kazuyuki; Morita, Yoshio

2006-01-01

We report a case of probable dementia with Lewy bodies (DLB), showing reduplicative paramnesia (RP) and Capgras syndrome (CS). The patient, a right-handed 60 year-old male, began to show progressive dementia. At the age of 65, he showed fluctuating cognitive impairment and recurrent visual hallucinations. His SPECT demonstrated hypoperfusion not in the medial temporal cortices, but in the parieto-occipital lobes, where the right hemisphere was dominantly hypoperfused. He was diagnosed with probable DLB. In addition to recurrent visual hallucinations, he showed a sense of self- (or others) transfiguration, consciousness of something non-existent (Leibhaftige Bewusstheit; Jaspers, K.), and fluctuating visuo-spacial impairment. At the age of 67, he gradually complained of his duplicative wives "sosie". Finally he went so far as to talk about a nameless phantom boarder. We considered that RP and CS of this case comprised a sense of self-(or others) transfiguration, misidentification of important persons and places, and productive symptoms such as consciousness of something non-existent (Leibhaftige Bewusstheit) and visual hallucinations. The above mentioned symptoms might be originated not only from the disturbance of visuospacial recognition, which involves the limbic system (especially amygdala), medial frontal cortex, and right hemisphere of the brain, but also from the disturbance of recursive consciousness, due to diffusely damaged brain regions with Lewy body pathology. (Authors' abstract)

The optic pathway: the development of an eLearning animation.

PubMed

Cooper, Claire; Erolin, Caroline

2018-04-01

The optic pathway is responsible for sending visual information from the eyes to the brain via electrical impulses. It is essential that a sound understanding of this pathway is established in order to determine an accurate diagnosis concerning visual field defects. Although easy for trained neurologists to understand, it is an area which medical students repeatedly struggle to visualise. It is proposed that audio-visual teaching resources can improve students understanding of complex areas of importance. This article describes the development and evaluation of a short animation created for use in the undergraduate neurology curriculum at the University of Dundee School of Medicine.

Fear Conditioning in an Abdominal Pain Model: Neural Responses during Associative Learning and Extinction in Healthy Subjects

PubMed Central

Kattoor, Joswin; Gizewski, Elke R.; Kotsis, Vassilios; Benson, Sven; Gramsch, Carolin; Theysohn, Nina; Maderwald, Stefan; Forsting, Michael; Schedlowski, Manfred; Elsenbruch, Sigrid

2013-01-01

Fear conditioning is relevant for elucidating the pathophysiology of anxiety, but may also be useful in the context of chronic pain syndromes which often overlap with anxiety. Thus far, no fear conditioning studies have employed aversive visceral stimuli from the lower gastrointestinal tract. Therefore, we implemented a fear conditioning paradigm to analyze the conditioned response to rectal pain stimuli using fMRI during associative learning, extinction and reinstatement. In N = 21 healthy humans, visual conditioned stimuli (CS+) were paired with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS−) were presented without US. During extinction, all CSs were presented without US, whereas during reinstatement, a single, unpaired US was presented. In region-of-interest analyses, conditioned anticipatory neural activation was assessed along with perceived CS-US contingency and CS unpleasantness. Fear conditioning resulted in significant contingency awareness and valence change, i.e., learned unpleasantness of a previously neutral stimulus. This was paralleled by anticipatory activation of the anterior cingulate cortex, the somatosensory cortex and precuneus (all during early acquisition) and the amygdala (late acquisition) in response to the CS+. During extinction, anticipatory activation of the dorsolateral prefrontal cortex to the CS− was observed. In the reinstatement phase, a tendency for parahippocampal activation was found. Fear conditioning with rectal pain stimuli is feasible and leads to learned unpleasantness of previously neutral stimuli. Within the brain, conditioned anticipatory activations are seen in core areas of the central fear network including the amygdala and the anterior cingulate cortex. During extinction, conditioned responses quickly disappear, and learning of new predictive cue properties is paralleled by prefrontal activation. A tendency for parahippocampal activation during reinstatement could indicate a reactivation of the old memory trace. Together, these findings contribute to our understanding of aversive visceral learning and memory processes relevant to the pathophysiology of chronic abdominal pain. PMID:23468832

Radiocaesium derived FNPP1 accident in the ocean interior of the western North Pacific Ocean through 2016

NASA Astrophysics Data System (ADS)

Aoyama, Michio; Hamajima, Yasunori; Inomata, Yayoi; Kumamoto, Yuichiro; Oka, Eitarou; Tsubono, Takaki; Tsumune, Daisuke

2017-04-01

134Cs and 137Cs, hereafter radiocaesium, were released to the North Pacific Ocean by two major pathways, direct discharge and atmospheric deposition released from the TEPCO Fukushima Dai-ichi Nuclear Power Plant (FNPP1) accident in 2011. Activities of radiocaesium released from FNPP1 accident were measured as vertical profiles at 11 stations in 2011, at 14 stations in 2012, at 13 station in 2015 and at 6 stations in 2016 in the North Pacific Ocean to study transport processes in the ocean interior of the North Pacific Ocean. The major pathway from surface to ocean interior after injected in the ocean surface can be considered subduction of central mode water (CMW) and subduction of subduction of subtropical mode water (STMW) at potential densities of 26.1-26.3 for CMW and 25.1-25.3 for STMW, respectively. In June 2012 at 34°N-39°N along 165°E corresponding to the formation region of central mode water (CMW) located north of the Kuroshio Extension, 134Cs activity showed a maximum at around potential density= 26.3 kg m-3. 134Cs activity was higher in CMW than in any of the surrounding waters, including STMW. These observations also indicate that the most effective pathway by which FNPP1-derived radiocaesium is introduced into the ocean interior on a 1-year time scale is CMW formation and subduction. In June-July 2015 at 36 deg. N-44 deg. N along 165 deg. E and June 2016 at 38-40N, 165-170 deg. E, there are only very week signal of subduction of Fukushima derived radiocaesium at in the CMW formation region, which means that subducted radiocaesium might have moved eastward from this region. In June 2012, 134Cs activity reached a maximum of 6.12 ± 0.50 Bq m-3 at a 151-m depth (potential density, 25.3 kg m-3) at 29 deg. N, 165 deg. E. This subsurface maximum, which was also observed along 149°E, might reflect the southward transport of FNPP1-derived radiocaesium in association with the formation and subduction of subtropical mode water (STMW) from the region south of the Kuroshio Extension. In June 2015, FNPP1 derived radiocaesium spread over the entire subtropical gyre between 20 deg. N to 32 deg. N along 165 deg. E. In the south of Kuroshio Extension at 30 deg. N to 32 deg. N, 144 deg. E to 147 deg. E, 134Cs activity showed maximum at STMW, of which depth is around 400 meters, in 2014, 2015 and 2016. 134Cs activity , of which activities were decay corrected to March 2011, at 400 meters depth at this region were almost stable during these three years and the activities were 3.60 ± 0.80 Bq m-3 in June 2014, 3.65 ± 0.89 Bq m-3 in October 2015, 3.82 ± 0.85Bq m-3 in June 2016, respectively. This might indicate that FNPP1 derived radiocaesium subducted into ocean interior due to STMW formation are already recirculated to south of Kuroshio Extension in the subtropical gyre.

The ADMA/DDAH/NO pathway in human vein endothelial cells exposed to arsenite.

PubMed

Osorio-Yáñez, Citlalli; Chin-Chan, Miguel; Sánchez-Peña, Luz C; Atzatzi-Aguilar, Octavio G; Olivares-Reyes, Jesus A; Segovia, José; Del Razo, Luz M

2017-08-01

Inorganic arsenic (iAs) exposure is related to cardiovascular disease, which is characterized by endothelial dysfunction and nitric oxide (NO) depletion. The mechanisms underlying NO depletion as related to iAs exposure are not fully understood. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), might be a molecular target of iAs. ADMA concentrations are regulated by proteins involved in its synthesis (arginine methyl transferase 1 [PRMT-1]) and degradation (dimethylarginine dimethylaminohydrolase [DDAH]). Both, ADMA and NO are susceptible to oxidative stress. We aimed to determine the ADMA/DDAH/NO pathway in human vein endothelial cells (HUVEC-CS) exposed to arsenite. We exposed HUVEC-CS cells to 1, 2.5 and 5μM of arsenite for 24h. We proved that arsenite at 5μM was able to decrease NO levels with an associated increase in ADMA and depletion of l-arginine in HUVEC-CS cells. We also found a decrease in DDAH-1 protein expression with 5μM of arsenite compared to the control group. However, we did not observe significant differences in PRMT-1 protein expression at any of the concentrations of arsenite employed. Finally, arsenite (2.5 and 5μM) increased NADPH oxidase 4 protein levels compared with the control group. We conclude that ADMA, l-arginine and DDAH are involved in NO depletion produced by arsenite, and that the mechanism is related to oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Inversion of Sensory Processing by Feedback Pathways: A Model of Visual Cognitive Functions.

ERIC Educational Resources Information Center

Harth, E.; And Others

1987-01-01

Explains the hierarchic structure of the mammalian visual system. Proposes a model in which feedback pathways serve to modify sensory stimuli in ways that enhance and complete sensory input patterns. Investigates the functioning of the system through computer simulations. (ML)

Contralateral Bias of High Spatial Frequency Tuning and Cardinal Direction Selectivity in Mouse Visual Cortex

PubMed Central

Zeitoun, Jack H.; Kim, Hyungtae

2017-01-01

Binocular mechanisms for visual processing are thought to enhance spatial acuity by combining matched input from the two eyes. Studies in the primary visual cortex of carnivores and primates have confirmed that eye-specific neuronal response properties are largely matched. In recent years, the mouse has emerged as a prominent model for binocular visual processing, yet little is known about the spatial frequency tuning of binocular responses in mouse visual cortex. Using calcium imaging in awake mice of both sexes, we show that the spatial frequency preference of cortical responses to the contralateral eye is ∼35% higher than responses to the ipsilateral eye. Furthermore, we find that neurons in binocular visual cortex that respond only to the contralateral eye are tuned to higher spatial frequencies. Binocular neurons that are well matched in spatial frequency preference are also matched in orientation preference. In contrast, we observe that binocularly mismatched cells are more mismatched in orientation tuning. Furthermore, we find that contralateral responses are more direction-selective than ipsilateral responses and are strongly biased to the cardinal directions. The contralateral bias of high spatial frequency tuning was found in both awake and anesthetized recordings. The distinct properties of contralateral cortical responses may reflect the functional segregation of direction-selective, high spatial frequency-preferring neurons in earlier stages of the central visual pathway. Moreover, these results suggest that the development of binocularity and visual acuity may engage distinct circuits in the mouse visual system. SIGNIFICANCE STATEMENT Seeing through two eyes is thought to improve visual acuity by enhancing sensitivity to fine edges. Using calcium imaging of cellular responses in awake mice, we find surprising asymmetries in the spatial processing of eye-specific visual input in binocular primary visual cortex. The contralateral visual pathway is tuned to higher spatial frequencies than the ipsilateral pathway. At the highest spatial frequencies, the contralateral pathway strongly prefers to respond to visual stimuli along the cardinal (horizontal and vertical) axes. These results suggest that monocular, and not binocular, mechanisms set the limit of spatial acuity in mice. Furthermore, they suggest that the development of visual acuity and binocularity in mice involves different circuits. PMID:28924011

Identifying and characterising cerebral visual impairment in children: a review.

PubMed

Philip, Swetha Sara; Dutton, Gordon N

2014-05-01

Cerebral visual impairment (CVI) comprises visual malfunction due to retro-chiasmal visual and visual association pathway pathology. This can be isolated or accompany anterior visual pathway dysfunction. It is a major cause of low vision in children in the developed and developing world due to increasing survival in paediatric and neonatal care. CVI can present in many combinations and degrees. There are multiple causes and it is common in children with cerebral palsy. CVI can be identified easily, if a structured approach to history-taking is employed. This review describes the features of CVI and describes practical management strategies aimed at helping affected children. A literature review was undertaken using 'Medline' and 'Pubmed'. Search terms included cerebral visual impairment, cortical visual impairment, dorsal stream dysfunction and visual function in cerebral palsy. © 2014 The Authors. Clinical and Experimental Optometry © 2014 Optometrists Association Australia.

HPIminer: A text mining system for building and visualizing human protein interaction networks and pathways.

PubMed

Subramani, Suresh; Kalpana, Raja; Monickaraj, Pankaj Moses; Natarajan, Jeyakumar

2015-04-01

The knowledge on protein-protein interactions (PPI) and their related pathways are equally important to understand the biological functions of the living cell. Such information on human proteins is highly desirable to understand the mechanism of several diseases such as cancer, diabetes, and Alzheimer's disease. Because much of that information is buried in biomedical literature, an automated text mining system for visualizing human PPI and pathways is highly desirable. In this paper, we present HPIminer, a text mining system for visualizing human protein interactions and pathways from biomedical literature. HPIminer extracts human PPI information and PPI pairs from biomedical literature, and visualize their associated interactions, networks and pathways using two curated databases HPRD and KEGG. To our knowledge, HPIminer is the first system to build interaction networks from literature as well as curated databases. Further, the new interactions mined only from literature and not reported earlier in databases are highlighted as new. A comparative study with other similar tools shows that the resultant network is more informative and provides additional information on interacting proteins and their associated networks. Copyright © 2015 Elsevier Inc. All rights reserved.

Visual processing in the central bee brain.

PubMed

Paulk, Angelique C; Dacks, Andrew M; Phillips-Portillo, James; Fellous, Jean-Marc; Gronenberg, Wulfila

2009-08-12

Visual scenes comprise enormous amounts of information from which nervous systems extract behaviorally relevant cues. In most model systems, little is known about the transformation of visual information as it occurs along visual pathways. We examined how visual information is transformed physiologically as it is communicated from the eye to higher-order brain centers using bumblebees, which are known for their visual capabilities. We recorded intracellularly in vivo from 30 neurons in the central bumblebee brain (the lateral protocerebrum) and compared these neurons to 132 neurons from more distal areas along the visual pathway, namely the medulla and the lobula. In these three brain regions (medulla, lobula, and central brain), we examined correlations between the neurons' branching patterns and their responses primarily to color, but also to motion stimuli. Visual neurons projecting to the anterior central brain were generally color sensitive, while neurons projecting to the posterior central brain were predominantly motion sensitive. The temporal response properties differed significantly between these areas, with an increase in spike time precision across trials and a decrease in average reliable spiking as visual information processing progressed from the periphery to the central brain. These data suggest that neurons along the visual pathway to the central brain not only are segregated with regard to the physical features of the stimuli (e.g., color and motion), but also differ in the way they encode stimuli, possibly to allow for efficient parallel processing to occur.

Accumulation of sphingoid bases and sphingoid base 1-phosphates: A possible mechanism for Fusarium verticillioides corn-seedling disease

USDA-ARS?s Scientific Manuscript database

Sphingolipids are important structural components of membranes involved in signaling pathways that regulate cell growth and death. Fumonisins (FB) are water soluble mycotoxins produced by F. verticillioides, which is parasitic to corn. FBs are inhibitors of ceramide synthase (CS), a key enzyme in sp...

All Roads Lead to Computing: Making, Participatory Simulations, and Social Computing as Pathways to Computer Science

ERIC Educational Resources Information Center

Brady, Corey; Orton, Kai; Weintrop, David; Anton, Gabriella; Rodriguez, Sebastian; Wilensky, Uri

2017-01-01

Computer science (CS) is becoming an increasingly diverse domain. This paper reports on an initiative designed to introduce underrepresented populations to computing using an eclectic, multifaceted approach. As part of a yearlong computing course, students engage in Maker activities, participatory simulations, and computing projects that…

DNA packaging and the pathway of bacteriophage T4 head assembly.

PubMed Central

Hsiao, C L; Black, L W

1977-01-01

A cold-sensitive mutation in the structural gene for a minor phage T4 capsid protein (p20) leads to formation of heads containing p20 and cleaved head proteins and empty of DNA. Such heads can be filled with DNA and converted to active phages in vivo uponshift to high temperature. It appears that p20 has two distinct roles in head assembly: first, in construction of the prehead shell (blocked by ts and am mutation) and, second,in DNA packaging (blocked by cs mutation). The latter function is closely associated with gene 17 product, previously known to be required for DNA packagaing. Temperature shift studies of cs-ts double mutants and other observations allow determination of phage function required for DNA packaging. Contrary to previous proposals, we find that T4 DNA packaging is not directly coupled to and can follow DNA synthesis, protein cleavage, prehead core removal, and gene 21-mediated cleavage-induced increase in head volume. Our evidence suggests that an altered head assembly pathway exists and that DNA packaging is probably initiated by DNA-capsid (p20) interaction. Images PMID:269421

Immunostimulating activity of maysin isolated from corn silk in murine RAW 264.7 macrophages.

PubMed

Lee, Jisun; Kim, Sun-Lim; Lee, Seul; Chung, Mi Ja; Park, Yong Il

2014-07-01

Corn silk (CS) has long been consumed as a traditional herb in Korea. Maysin is a major flavonoid of CS. The effects of maysin on macrophage activation were evaluated, using the murine macrophage RAW 264.7 cells. Maysin was isolated from CS by methanol extraction, and preparative C18 reverse phase column chromatography. Maysin was nontoxic up to 100 μg/ml, and dose-dependently increased TNF-α secretion and iNOS production by 11.2- and 4.2-fold, respectively, compared to untreated control. The activation and subsequent nuclear translocation of NF-κB was substantially enhanced upon treatment with maysin (1-100 μg/ml). Maysin also stimulated the phosphorylation of Akt and MAPKs (ERK, JNK). These results indicated that maysin activates macrophages to secrete TNF-α and induce iNOS expression, via the activation of the Akt, NF-κB and MAPKs signaling pathways. These results suggest for the first time that maysin can be a new immunomodulator, enhancing the early innate immunity.

High wettability of liquid caesium iodine with solid uranium dioxide.

PubMed

Kurosaki, Ken; Suzuki, Masanori; Uno, Masayoshi; Ishii, Hiroto; Kumagai, Masaya; Anada, Keito; Murakami, Yukihiro; Ohishi, Yuji; Muta, Hiroaki; Tanaka, Toshihiro; Yamanaka, Shinsuke

2017-09-13

In March 2011, the Fukushima Daiichi Nuclear Power Plant accident caused nuclear fuel to melt and the release of high-volatility fission products into the environment. Caesium and iodine caused environmental contamination and public exposure. Certain fission-product behaviours remain unclear. We found experimentally that liquid CsI disperses extremely favourably toward solid UO 2 , exhibiting a contact angle approaching zero. We further observed the presence of CsI several tens of micrometres below the surface of the solid UO 2 sample, which would be caused by the infiltration of pores network by liquid CsI. Thus, volatile fission products released from molten nuclear fuels with complex internal composition and external structure migrate or evaporate to varying extents, depending on the nature of the solid-liquid interface and the fuel material surface, which becomes the pathway for the released fission products. Introducing the concept of the wettability of liquid chemical species of fission products in contact with solid fuels enabled developing accurate behavioural assessments of volatile fission products released by nuclear fuel.

Magnocellular pathway for rotation invariant Neocognitron.

PubMed

Ting, C H

1993-03-01

In the mammalian visual system, magnocellular pathway and parvocellular pathway cooperatively process visual information in parallel. The magnocellular pathway is more global and less particular about the details while the parvocellular pathway recognizes objects based on the local features. In many aspects, Neocognitron may be regarded as the artificial analogue of the parvocellular pathway. It is interesting then to model the magnocellular pathway. In order to achieve "rotation invariance" for Neocognitron, we propose a neural network model after the magnocellular pathway and expand its roles to include surmising the orientation of the input pattern prior to recognition. With the incorporation of the magnocellular pathway, a basic shift in the original paradigm has taken place. A pattern is now said to be recognized when and only when one of the winners of the magnocellular pathway is validified by the parvocellular pathway. We have implemented the magnocellular pathway coupled with Neocognitron parallel on transputers; our simulation programme is now able to recognize numerals in arbitrary orientation.

"That Tricky Subject": The Integration of Contextual Studies in Pre-Degree Art and Design Education

ERIC Educational Resources Information Center

Rintoul, Jenny; James, David

2017-01-01

Contextual studies (CS), "theory", "visual culture" or "art history" (amongst other labels) refer to a regular and often compulsory feature in art and design education. However, this takes many forms and can sit in a variety of relationships with the practical elements of such courses. This article is based on mixed…

Influence of Alice 3: Reducing the Hurdles to Success in a CS1 Programming Course

ERIC Educational Resources Information Center

Daly, Tebring

2013-01-01

Learning the syntax, semantics, and concepts behind software engineering can be a challenging task for many individuals. This paper examines the Alice 3 software, a three-dimensional visual environment for teaching programming concepts, to determine if it is an effective tool for improving student achievement, raising self-efficacy, and engaging…

Pathview: an R/Bioconductor package for pathway-based data integration and visualization.

PubMed

Luo, Weijun; Brouwer, Cory

2013-07-15

Pathview is a novel tool set for pathway-based data integration and visualization. It maps and renders user data on relevant pathway graphs. Users only need to supply their data and specify the target pathway. Pathview automatically downloads the pathway graph data, parses the data file, maps and integrates user data onto the pathway and renders pathway graphs with the mapped data. Although built as a stand-alone program, Pathview may seamlessly integrate with pathway and functional analysis tools for large-scale and fully automated analysis pipelines. The package is freely available under the GPLv3 license through Bioconductor and R-Forge. It is available at http://bioconductor.org/packages/release/bioc/html/pathview.html and at http://Pathview.r-forge.r-project.org/. luo_weijun@yahoo.com Supplementary data are available at Bioinformatics online.

Seeing More by Showing Less: Orientation-Dependent Transparency Rendering for Fiber Tractography Visualization

PubMed Central

Tax, Chantal M. W.; Chamberland, Maxime; van Stralen, Marijn; Viergever, Max A.; Whittingstall, Kevin; Fortin, David; Descoteaux, Maxime; Leemans, Alexander

2015-01-01

Fiber tractography plays an important role in exploring the architectural organization of fiber trajectories, both in fundamental neuroscience and in clinical applications. With the advent of diffusion MRI (dMRI) approaches that can also model “crossing fibers”, the complexity of the fiber network as reconstructed with tractography has increased tremendously. Many pathways interdigitate and overlap, which hampers an unequivocal 3D visualization of the network and impedes an efficient study of its organization. We propose a novel fiber tractography visualization approach that interactively and selectively adapts the transparency rendering of fiber trajectories as a function of their orientation to enhance the visibility of the spatial context. More specifically, pathways that are oriented (locally or globally) along a user-specified opacity axis can be made more transparent or opaque. This substantially improves the 3D visualization of the fiber network and the exploration of tissue configurations that would otherwise be largely covered by other pathways. We present examples of fiber bundle extraction and neurosurgical planning cases where the added benefit of our new visualization scheme is demonstrated over conventional fiber visualization approaches. PMID:26444010

MOST-visualization: software for producing automated textbook-style maps of genome-scale metabolic networks.

PubMed

Kelley, James J; Maor, Shay; Kim, Min Kyung; Lane, Anatoliy; Lun, Desmond S

2017-08-15

Visualization of metabolites, reactions and pathways in genome-scale metabolic networks (GEMs) can assist in understanding cellular metabolism. Three attributes are desirable in software used for visualizing GEMs: (i) automation, since GEMs can be quite large; (ii) production of understandable maps that provide ease in identification of pathways, reactions and metabolites; and (iii) visualization of the entire network to show how pathways are interconnected. No software currently exists for visualizing GEMs that satisfies all three characteristics, but MOST-Visualization, an extension of the software package MOST (Metabolic Optimization and Simulation Tool), satisfies (i), and by using a pre-drawn overview map of metabolism based on the Roche map satisfies (ii) and comes close to satisfying (iii). MOST is distributed for free on the GNU General Public License. The software and full documentation are available at http://most.ccib.rutgers.edu/. dslun@rutgers.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Magnetic resonance in studies of glaucoma

PubMed Central

Fiedorowicz, Michał; Dyda, Wojciech; Rejdak, Robert; Grieb, Paweł

2011-01-01

Summary Glaucoma is the second leading cause of blindness. It affects retinal ganglion cells and the optic nerve. However, there is emerging evidence that glaucoma also affects other components of the visual pathway and visual cortex. There is a need to employ new methods of in vivo brain evaluation to characterize these changes. Magnetic resonance (MR) techniques are well suited for this purpose. We review data on the MR evaluation of the visual pathway and the use of MR techniques in the study of glaucoma, both in humans and in animal models. These studies demonstrated decreases in optic nerve diameter, localized white matter loss and decrease in visual cortex density. Studies on rats employing manganese-enhanced MRI showed that axonal transport in the optic nerve is affected. Diffusion tensor MRI revealed signs of degeneration of the optic pathway. Functional MRI showed decreased response of the visual cortex after stimulation of the glaucomatous eye. Magnetic resonance spectroscopy demonstrated changes in metabolite levels in the visual cortex in a rat model of glaucoma, although not in glaucoma patients. Further applications of MR techniques in studies of glaucomatous brains are indicated. PMID:21959626

Seeing More by Showing Less: Orientation-Dependent Transparency Rendering for Fiber Tractography Visualization.

PubMed

Tax, Chantal M W; Chamberland, Maxime; van Stralen, Marijn; Viergever, Max A; Whittingstall, Kevin; Fortin, David; Descoteaux, Maxime; Leemans, Alexander

2015-01-01

Fiber tractography plays an important role in exploring the architectural organization of fiber trajectories, both in fundamental neuroscience and in clinical applications. With the advent of diffusion MRI (dMRI) approaches that can also model "crossing fibers", the complexity of the fiber network as reconstructed with tractography has increased tremendously. Many pathways interdigitate and overlap, which hampers an unequivocal 3D visualization of the network and impedes an efficient study of its organization. We propose a novel fiber tractography visualization approach that interactively and selectively adapts the transparency rendering of fiber trajectories as a function of their orientation to enhance the visibility of the spatial context. More specifically, pathways that are oriented (locally or globally) along a user-specified opacity axis can be made more transparent or opaque. This substantially improves the 3D visualization of the fiber network and the exploration of tissue configurations that would otherwise be largely covered by other pathways. We present examples of fiber bundle extraction and neurosurgical planning cases where the added benefit of our new visualization scheme is demonstrated over conventional fiber visualization approaches.

Rapid prefrontal cortex activation towards aversively paired faces and enhanced contingency detection are observed in highly trait-anxious women under challenging conditions

PubMed Central

Rehbein, Maimu Alissa; Wessing, Ida; Zwitserlood, Pienie; Steinberg, Christian; Eden, Annuschka Salima; Dobel, Christian; Junghöfer, Markus

2015-01-01

Relative to healthy controls, anxiety-disorder patients show anomalies in classical conditioning that may either result from, or provide a risk factor for, clinically relevant anxiety. Here, we investigated whether healthy participants with enhanced anxiety vulnerability show abnormalities in a challenging affective-conditioning paradigm, in which many stimulus-reinforcer associations had to be acquired with only few learning trials. Forty-seven high and low trait-anxious females underwent MultiCS conditioning, in which 52 different neutral faces (CS+) were paired with an aversive noise (US), while further 52 faces (CS−) remained unpaired. Emotional learning was assessed by evaluative (rating), behavioral (dot-probe, contingency report), and neurophysiological (magnetoencephalography) measures before, during, and after learning. High and low trait-anxious groups did not differ in evaluative ratings or response priming before or after conditioning. High trait-anxious women, however, were better than low trait-anxious women at reporting CS+/US contingencies after conditioning, and showed an enhanced prefrontal cortex (PFC) activation towards CS+ in the M1 (i.e., 80–117 ms) and M170 time intervals (i.e., 140–160 ms) during acquisition. These effects in MultiCS conditioning observed in individuals with elevated trait anxiety are consistent with theories of enhanced conditionability in anxiety vulnerability. Furthermore, they point towards increased threat monitoring and detection in highly trait-anxious females, possibly mediated by alterations in visual working memory. PMID:26113814

Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging.

PubMed

Lilja, Ylva; Gustafsson, Oscar; Ljungberg, Maria; Starck, Göran; Lindblom, Bertil; Skoglund, Thomas; Bergquist, Henrik; Jakobsson, Karl-Erik; Nilsson, Daniel

2017-09-01

OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p < 0.05 and r = 0.48, p < 0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = -0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial diffusivity differed significantly between controls and patients with VFD, both before and after surgery (p < 0.05); however, no difference was found between patients with and without VFD. Based on the axial diffusivity and fractional anisotropy, a prediction model classified all patients with VFD correctly (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and 17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect pathology and degree of injury in the anterior visual pathways that were compressed by pituitary adenomas. The correlation between radial diffusivity and visual impairment may reflect a gradual demyelination in the visual pathways caused by an increased tumor effect. The low level of axial diffusivity found in the patient group may represent early atrophy in the visual pathways, detectable on DTI but not by conventional methods. DTI may provide objective data, detect early signs of injury, and be an additional diagnostic tool for determining indication for surgery in cases of pituitary adenomas.

Relationship between cortical state and spiking activity in the lateral geniculate nucleus of marmosets

PubMed Central

Pietersen, Alexander N.J.; Cheong, Soon Keen; Munn, Brandon; Gong, Pulin; Solomon, Samuel G.

2017-01-01

Key points How parallel are the primate visual pathways? In the present study, we demonstrate that parallel visual pathways in the dorsal lateral geniculate nucleus (LGN) show distinct patterns of interaction with rhythmic activity in the primary visual cortex (V1).In the V1 of anaesthetized marmosets, the EEG frequency spectrum undergoes transient changes that are characterized by fluctuations in delta‐band EEG power.We show that, on multisecond timescales, spiking activity in an evolutionary primitive (koniocellular) LGN pathway is specifically linked to these slow EEG spectrum changes. By contrast, on subsecond (delta frequency) timescales, cortical oscillations can entrain spiking activity throughout the entire LGN.Our results are consistent with the hypothesis that, in waking animals, the koniocellular pathway selectively participates in brain circuits controlling vigilance and attention. Abstract The major afferent cortical pathway in the visual system passes through the dorsal lateral geniculate nucleus (LGN), where nerve signals originating in the eye can first interact with brain circuits regulating visual processing, vigilance and attention. In the present study, we investigated how ongoing and visually driven activity in magnocellular (M), parvocellular (P) and koniocellular (K) layers of the LGN are related to cortical state. We recorded extracellular spiking activity in the LGN simultaneously with local field potentials (LFP) in primary visual cortex, in sufentanil‐anaesthetized marmoset monkeys. We found that asynchronous cortical states (marked by low power in delta‐band LFPs) are linked to high spike rates in K cells (but not P cells or M cells), on multisecond timescales. Cortical asynchrony precedes the increases in K cell spike rates by 1–3 s, implying causality. At subsecond timescales, the spiking activity in many cells of all (M, P and K) classes is phase‐locked to delta waves in the cortical LFP, and more cells are phase‐locked during synchronous cortical states than during asynchronous cortical states. The switch from low‐to‐high spike rates in K cells does not degrade their visual signalling capacity. By contrast, during asynchronous cortical states, the fidelity of visual signals transmitted by K cells is improved, probably because K cell responses become less rectified. Overall, the data show that slow fluctuations in cortical state are selectively linked to K pathway spiking activity, whereas delta‐frequency cortical oscillations entrain spiking activity throughout the entire LGN, in anaesthetized marmosets. PMID:28116750

What does the Cantril Ladder measure in adolescence?

PubMed

Mazur, Joanna; Szkultecka-Dębek, Monika; Dzielska, Anna; Drozd, Mariola; Małkowska-Szkutnik, Agnieszka

2018-01-01

The Cantril Scale (CS) is a simple visual scale which makes it possible to assess general life satisfaction. The result may depend on the health, living, and studying conditions, and quality of social relations. The objective of this study is to identify key factors influencing the CS score in Polish adolescents. The survey comprised 1,423 parent-child pairs (54% girls; age range: 10-17; 67.3% urban inhabitants; 89.4% of parents were mothers). Linear and logistic models were estimated; the latter used alternative divisions into "satisfied" and "dissatisfied" with life. In addition to age and gender, child-reported KIDSCREEN-52 quality of life indexes were taken into account, along with some information provided by parents - child physical (CSHCN) and mental (SDQ) health, and family socio-economic conditions. According to the linear model, nine independent predictors, including six dimensions of KIDSCREEN-52, explain 47.2% of the variability of life satisfaction on the Cantril Scale. Self-perception was found to have a dominating influence (Δ R 2 = 0.301, p < 0.001). Important CS predictors also included Psychological Well-being (Δ R 2 = 0.088, p < 0.001) and Parent Relations (Δ R 2 = 0.041, p < 0.001). The impact of socioeconomic factors was more visible in boys and in older adolescents. According to logistic models, the key factors enhancing the chance of higher life satisfaction are Moods and Emotions (cut-off point CS > 5) and School Environment (CS > 8 points). None of the models indicated a relationship between the CS and physical health. The Cantril Scale can be considered a useful measurement tool in a broad approach to psychosocial adolescent health.

Variability of coronary venous anatomy in patients undergoing cardiac resynchronization therapy: a high-speed rotational venography study.

PubMed

Blendea, Dan; Shah, Ravi V; Auricchio, Angelo; Nandigam, Veena; Orencole, Mary; Heist, E Kevin; Reddy, Vivek Y; McPherson, Craig A; Ruskin, Jeremy N; Singh, Jagmeet P

2007-09-01

Imaging the coronary venous (CV) tree to delineate the coronary sinus and its tributaries can facilitate electrophysiological procedures, such as cardiac resynchronization therapy (CRT) and catheter ablation. Venography also allows visualization of the left atrial (LA) veins, which may be a potential conduit for ablative or pacing strategies given their proximity to foci that can trigger atrial fibrillation. The aim of this study was to provide a detailed description of CV anatomy using rotational venography in patients undergoing CRT. Coronary sinus (CS) size and the presence, size, and angulation of its tributaries were determined from the analysis of rotational CV angiograms from 51 patients (age 68 +/- 11 years; n = 12 women) undergoing CRT. The CS, posterior veins, and lateral veins were identified in 100%, 76%, and 91% of patients. Lateral veins were less prevalent in patients with a history of lateral myocardial infarction than in patients without such a history (33% vs. 96%; P = .014). The diameters of the CS and its tributaries were fairly variable (7.3-18.9 mm for CS, 1.3-10.5 mm for CS tributaries). The CS was larger in men than in women and in cases of ischemic than in cases of nonischemic cardiomyopathy (all P <.05). The vein of Marshall, the most constant LA vein, was identified in 37 patients; its diameter is 1.7 +/- 0.5 mm, and its takeoff angle is 154 degrees +/- 15 degrees , making the vein potentially accessible for cannulation. Differences in CV anatomy that are related to either gender or coronary artery disease could have important practical implications during the left ventricular lead implantation. The anatomical features of the vein of Marshall make it a feasible potential conduit for epicardial LA pacing.

On the usefulness of 'what' and 'where' pathways in vision.

PubMed

de Haan, Edward H F; Cowey, Alan

2011-10-01

The primate visual brain is classically portrayed as a large number of separate 'maps', each dedicated to the processing of specific visual cues, such as colour, motion or faces and their many features. In order to understand this fractionated architecture, the concept of cortical 'pathways' or 'streams' was introduced. In the currently prevailing view, the different maps are organised hierarchically into two major pathways, one involved in recognition and memory (the ventral stream or 'what' pathway) and the other in the programming of action (the dorsal stream or 'where' pathway). In this review, we question this heuristically influential but potentially misleading linear hierarchical pathway model and argue instead for a 'patchwork' or network model. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pathview Web: user friendly pathway visualization and data integration.

PubMed

Luo, Weijun; Pant, Gaurav; Bhavnasi, Yeshvant K; Blanchard, Steven G; Brouwer, Cory

2017-07-03

Pathway analysis is widely used in omics studies. Pathway-based data integration and visualization is a critical component of the analysis. To address this need, we recently developed a novel R package called Pathview. Pathview maps, integrates and renders a large variety of biological data onto molecular pathway graphs. Here we developed the Pathview Web server, as to make pathway visualization and data integration accessible to all scientists, including those without the special computing skills or resources. Pathview Web features an intuitive graphical web interface and a user centered design. The server not only expands the core functions of Pathview, but also provides many useful features not available in the offline R package. Importantly, the server presents a comprehensive workflow for both regular and integrated pathway analysis of multiple omics data. In addition, the server also provides a RESTful API for programmatic access and conveniently integration in third-party software or workflows. Pathview Web is openly and freely accessible at https://pathview.uncc.edu/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Two speed factors of visual recognition independently correlated with fluid intelligence.

PubMed

Tachibana, Ryosuke; Namba, Yuri; Noguchi, Yasuki

2014-01-01

Growing evidence indicates a moderate but significant relationship between processing speed in visuo-cognitive tasks and general intelligence. On the other hand, findings from neuroscience proposed that the primate visual system consists of two major pathways, the ventral pathway for objects recognition and the dorsal pathway for spatial processing and attentive analysis. Previous studies seeking for visuo-cognitive factors of human intelligence indicated a significant correlation between fluid intelligence and the inspection time (IT), an index for a speed of object recognition performed in the ventral pathway. We thus presently examined a possibility that neural processing speed in the dorsal pathway also represented a factor of intelligence. Specifically, we used the mental rotation (MR) task, a popular psychometric measure for mental speed of spatial processing in the dorsal pathway. We found that the speed of MR was significantly correlated with intelligence scores, while it had no correlation with one's IT (recognition speed of visual objects). Our results support the new possibility that intelligence could be explained by two types of mental speed, one related to object recognition (IT) and another for manipulation of mental images (MR).