A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation.

PubMed

Ballios, Brian G; Cooke, Michael J; Donaldson, Laura; Coles, Brenda L K; Morshead, Cindi M; van der Kooy, Derek; Shoichet, Molly S

2015-06-09

The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC) and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC)-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs). The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Orientation-selective Responses in the Mouse Lateral Geniculate Nucleus

PubMed Central

Zhao, Xinyu; Chen, Hui; Liu, Xiaorong

2013-01-01

The dorsal lateral geniculate nucleus (dLGN) receives visual information from the retina and transmits it to the cortex. In this study, we made extracellular recordings in the dLGN of both anesthetized and awake mice, and found that a surprisingly high proportion of cells were selective for stimulus orientation. The orientation selectivity of dLGN cells was unchanged after silencing the visual cortex pharmacologically, indicating that it is not due to cortical feedback. The orientation tuning of some dLGN cells correlated with their elongated receptive fields, while in others orientation selectivity was observed despite the fact that their receptive fields were circular, suggesting that their retinal input might already be orientation selective. Consistently, we revealed orientation/axis-selective ganglion cells in the mouse retina using multielectrode arrays in an in vitro preparation. Furthermore, the orientation tuning of dLGN cells was largely maintained at different stimulus contrasts, which could be sufficiently explained by a simple linear feedforward model. We also compared the degree of orientation selectivity in different visual structures under the same recording condition. Compared with the dLGN, orientation selectivity is greatly improved in the visual cortex, but is similar in the superior colliculus, another major retinal target. Together, our results demonstrate prominent orientation selectivity in the mouse dLGN, which may potentially contribute to visual processing in the cortex. PMID:23904611

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

Corneal Collagen Crosslinking Combined with Phototherapeutic Keratectomy and Photorefractive Keratectomy for Corneal Ectasia after Laser in situ Keratomileusis.

PubMed

Zhu, Wei; Han, Yunfei; Cui, Changxia; Xu, Wenwen; Wang, Xuan; Dou, Xiaoxiao; Xu, Linlin; Xu, Yanyun; Mu, Guoying

2018-01-01

The aim of this study was to analyze the effects of corneal crosslinking (CXL) combined with phototherapeutic keratectomy (PTK) and photorefractive keratectomy (PRK) in halting the progression and improving the visual function of corneal ectasia after laser in situ keratomileusis (LASIK). PTK-PRK-CXL was performed on 14 eyes of 14 patients who developed corneal ectasia after LASIK. The visual acuity, spherical refraction and cylinder, corneal topography indices, thinnest corneal thickness (TCT), and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. The mean uncorrected visual acuity improved significantly from 0.64 ± 0.36 logMAR preoperatively to 0.19 ± 0.12 logMAR at 12 months of follow-up (p < 0.001), while the mean best corrected visual acuity improved from 0.21 ± 0.14 logMAR at baseline to 0.04 ± 0.10 logMAR at 12 months postoperatively (p < 0.001). A significant decrease was observed in Kmax and Kmean values from 52.51 ± 6.74 and 43.55 ± 3.37 D at baseline to 45.72 ± 5.18 (p < 0.001) and 40.60 ± 3.05 D (p < 0.001) at the 1-year follow-up. The mean TCT decreased significantly from 419.07 ± 36.56 µm before treatment to 320.93 ± 39.78 µm at 12 months of follow-up (p < 0.001), and there was no significant endothelial cell loss (p > 0.05) beyond 6 months after treatment. PTK-PRK-CXL is a promising procedure to halt the progression of post-LASIK keratectasia with significant visual quality improvement. © 2018 S. Karger AG, Basel.

Non-invasive intravital imaging of cellular differentiation with a bright red-excitable fluorescent protein

PubMed Central

Chu, Jun; Haynes, Russell D; Corbel, Stéphane Y; Li, Pengpeng; González-González, Emilio; Burg, John S; Ataie, Niloufar J; Lam, Amy J; Cranfill, Paula J; Baird, Michelle A; Davidson, Michael W; Ng, Ho-Leung; Garcia, K Christopher; Contag, Christopher H; Shen, Kang; Blau, Helen M; Lin, Michael Z

2014-01-01

A method for non-invasive visualization of genetically labelled cells in animal disease models with micron-level resolution would greatly facilitate development of cell-based therapies. Imaging of fluorescent proteins (FPs) using red excitation light in the “optical window” above 600 nm is one potential method for visualizing implanted cells. However, previous efforts to engineer FPs with peak excitation beyond 600 nm have resulted in undesirable reductions in brightness. Here we report three new red-excitable monomeric FPs obtained by structure-guided mutagenesis of mNeptune, previously the brightest monomeric FP when excited beyond 600 nm. Two of these, mNeptune2 and mNeptune2.5, demonstrate improved maturation and brighter fluorescence, while the third, mCardinal, has a red-shifted excitation spectrum without reduction in brightness. We show that mCardinal can be used to non-invasively and longitudinally visualize the differentiation of myoblasts and stem cells into myocytes in living mice with high anatomical detail. PMID:24633408

Restoration of vision after transplantation of photoreceptors.

PubMed

Pearson, R A; Barber, A C; Rizzi, M; Hippert, C; Xue, T; West, E L; Duran, Y; Smith, A J; Chuang, J Z; Azam, S A; Luhmann, U F O; Benucci, A; Sung, C H; Bainbridge, J W; Carandini, M; Yau, K-W; Sowden, J C; Ali, R R

2012-05-03

Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1−/− mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.

Visual acuity, refractive error, and endothelial cell density six months after Descemet stripping and automated endothelial keratoplasty (DSAEK).

PubMed

Koenig, Steven B; Covert, Douglas J; Dupps, William J; Meisler, David M

2007-07-01

To evaluate visual acuity, refractive outcomes, and endothelial cell density 6 months after Descemet stripping and automated endothelial keratoplasty (DSAEK). We performed an institutional review board-approved prospective study of a surgical case series of 34 patients at 2 institutions undergoing DSAEK for Fuchs endothelial dystrophy, pseudophakic bullous keratopathy, or aphakic bullous keratopathy with or without simultaneous phacoemulsification and intraocular lens implantation. Clinical outcomes, including best spectacle-corrected visual acuity (BSCVA), spherical equivalent refraction, and refractive astigmatism and topographic or keratometric astigmatism, were assessed at the 6-month postoperative examination and compared with preoperative values with paired Student t tests. The change in endothelial cell density from the eye bank examination to 6 months after transplantation was similarly evaluated. BSCVA averaged 20/99 preoperatively and 20/42 postoperatively (P < 0.0001). After DSAEK, 30 (88.2%) of 34 patients showed improved BSCVA, and 21 (61.8%) of the 34 patients achieved a BSCVA of 20/40 or better. For patients not undergoing simultaneous phacoemulsification and intraocular lens implantation, a hyperopic shift in refraction of 1.19 +/- 1.32 D was noted. Refractive astigmatism, topographic astigmatism, and keratometry showed no statistically significant change. Endothelial cell density of donor corneas averaged 2826 +/- 370 cells/mm, whereas the mean postoperative density was 1396 +/- 440 cells/mm. This finding corresponded to an average loss of 1426 cells/mm (50% loss; P = 0.0001). The first half of cases experienced an average cell loss of 1674 cells/mm (59% loss) compared with 1181 (41% loss) in the second half of cases (P = 0.005). Three (9%) of 34 grafts experienced iatrogenic graft failure and required reoperation with new donor tissue. Also, 9 (27%) of 34 grafts experienced dislocation in the early postoperative period and required repositioning. In this prospective study of DSAEK for bullous keratopathy and Fuchs endothelial corneal dystrophy, improvement of visual acuity was achieved with only a mild tendency toward hyperopic shift and without significant induced astigmatism. Endothelial cell loss was significant, however, and may be related to surgical experience.

Human corneal endothelial cell transplantation using nanocomposite gel sheet in bullous keratopathy.

PubMed

Parikumar, Periasamy; Haraguchi, Kazutoshi; Senthilkumar, Rajappa; Abraham, Samuel Jk

2018-01-01

Transplantation of in vitro expanded human corneal endothelial precursors (HCEP) cells using a nanocomposite (D25-NC) gel sheet as supporting material in bovine's cornea has been earlier reported. Herein we report the transplantation of HCEP cells derived from a cadaver donor cornea to three patients using the NC gel sheet. In three patients with bullous keratopathy, one after cataract surgery, one after trauma and another in the corneal graft, earlier performed for congenital corneal dystrophy, not amenable to medical management HCEP cells isolated from a human cadaver donor cornea in vitro expanded using a thermoreversible gelation polymer (TGP) for 26 days were divided into three equal portions and 1.6 × 10 5 HCEP cells were injected on to the endothelium of the affected eye in each patient using the D25-NC gel sheet as a supporting material. The sheets were removed after three days. The bullae in the cornea disappeared by the 3 rd -11 th post-operative day in all the three patients. Visual acuity improved from Perception of light (PL)+/Projection of rays (PR)+ to Hand movements (HM)+ in one of the patients by post-operative day 3 which was maintained at 18 months follow-up. At 18 months follow-up, in another patient the visual acuity had improved from HM+ to 6/60 while in the third patient, visual acuity remained HM+ as it was prior to HCEP transplantation. There were no adverse effects during the follow-up in any of the patients.

Computer-controlled impalement of cells in retinal wholemounts visualized by infrared CCD imaging on an inverted microscope.

PubMed

Reitsamer, H; Groiss, H P; Franz, M; Pflug, R

2000-01-31

We present a computer-guided microelectrode positioning system that is routinely used in our laboratory for intracellular electrophysiology and functional staining of retinal neurons. Wholemount preparations of isolated retina are kept in a superfusion chamber on the stage of an inverted microscope. Cells and layers of the retina are visualized by Nomarski interference contrast using infrared light in combination with a CCD camera system. After five-point calibration has been performed the electrode can be guided to any point inside the calibrated volume without moving the retina. Electrode deviations from target cells can be corrected by the software further improving the precision of this system. The good visibility of cells avoids prelabeling with fluorescent dyes and makes it possible to work under completely dark adapted conditions.

Improved Visualization of Glaucomatous Retinal Damage Using High-speed Ultrahigh-Resolution Optical Coherence Tomography

PubMed Central

Mumcuoglu, Tarkan; Wollstein, Gadi; Wojtkowski, Maciej; Kagemann, Larry; Ishikawa, Hiroshi; Gabriele, Michelle L.; Srinivasan, Vivek; Fujimoto, James G.; Duker, Jay S.; Schuman, Joel S.

2009-01-01

Purpose To test if improving optical coherence tomography (OCT) resolution and scanning speed improves the visualization of glaucomatous structural changes as compared with conventional OCT. Design Prospective observational case series. Participants Healthy and glaucomatous subjects in various stages of disease. Methods Subjects were scanned at a single visit with commercially available OCT (StratusOCT) and high-speed ultrahigh-resolution (hsUHR) OCT. The prototype hsUHR OCT had an axial resolution of 3.4 μm (3 times higher than StratusOCT), with an A-scan rate of 24 000 hertz (60 times faster than StratusOCT). The fast scanning rate allowed the acquisition of novel scanning patterns such as raster scanning, which provided dense coverage of the retina and optic nerve head. Main Outcome Measures Discrimination of retinal tissue layers and detailed visualization of retinal structures. Results High-speed UHR OCT provided a marked improvement in tissue visualization as compared with StratusOCT. This allowed the identification of numerous retinal layers, including the ganglion cell layer, which is specifically prone to glaucomatous damage. Fast scanning and the enhanced A-scan registration properties of hsUHR OCT provided maps of the macula and optic nerve head with unprecedented detail, including en face OCT fundus images and retinal nerve fiber layer thickness maps. Conclusion High-speed UHR OCT improves visualization of the tissues relevant to the detection and management of glaucoma. PMID:17884170

Bioorthogonal Metabolic Labeling of Nascent RNA in Neurons Improves the Sensitivity of Transcriptome-Wide Profiling.

PubMed

Zajaczkowski, Esmi L; Zhao, Qiong-Yi; Zhang, Zong Hong; Li, Xiang; Wei, Wei; Marshall, Paul R; Leighton, Laura J; Nainar, Sarah; Feng, Chao; Spitale, Robert C; Bredy, Timothy W

2018-06-15

Transcriptome-wide expression profiling of neurons has provided important insights into the underlying molecular mechanisms and gene expression patterns that transpire during learning and memory formation. However, there is a paucity of tools for profiling stimulus-induced RNA within specific neuronal cell populations. A bioorthogonal method to chemically label nascent (i.e., newly transcribed) RNA in a cell-type-specific and temporally controlled manner, which is also amenable to bioconjugation via click chemistry, was recently developed and optimized within conventional immortalized cell lines. However, its value within a more fragile and complicated cellular system such as neurons, as well as for transcriptome-wide expression profiling, has yet to be demonstrated. Here, we report the visualization and sequencing of activity-dependent nascent RNA derived from neurons using this labeling method. This work has important implications for improving transcriptome-wide expression profiling and visualization of nascent RNA in neurons, which has the potential to provide valuable insights into the mechanisms underlying neural plasticity, learning, and memory.

Visualization and correction of automated segmentation, tracking and lineaging from 5-D stem cell image sequences.

PubMed

Wait, Eric; Winter, Mark; Bjornsson, Chris; Kokovay, Erzsebet; Wang, Yue; Goderie, Susan; Temple, Sally; Cohen, Andrew R

2014-10-03

Neural stem cells are motile and proliferative cells that undergo mitosis, dividing to produce daughter cells and ultimately generating differentiated neurons and glia. Understanding the mechanisms controlling neural stem cell proliferation and differentiation will play a key role in the emerging fields of regenerative medicine and cancer therapeutics. Stem cell studies in vitro from 2-D image data are well established. Visualizing and analyzing large three dimensional images of intact tissue is a challenging task. It becomes more difficult as the dimensionality of the image data increases to include time and additional fluorescence channels. There is a pressing need for 5-D image analysis and visualization tools to study cellular dynamics in the intact niche and to quantify the role that environmental factors play in determining cell fate. We present an application that integrates visualization and quantitative analysis of 5-D (x,y,z,t,channel) and large montage confocal fluorescence microscopy images. The image sequences show stem cells together with blood vessels, enabling quantification of the dynamic behaviors of stem cells in relation to their vascular niche, with applications in developmental and cancer biology. Our application automatically segments, tracks, and lineages the image sequence data and then allows the user to view and edit the results of automated algorithms in a stereoscopic 3-D window while simultaneously viewing the stem cell lineage tree in a 2-D window. Using the GPU to store and render the image sequence data enables a hybrid computational approach. An inference-based approach utilizing user-provided edits to automatically correct related mistakes executes interactively on the system CPU while the GPU handles 3-D visualization tasks. By exploiting commodity computer gaming hardware, we have developed an application that can be run in the laboratory to facilitate rapid iteration through biological experiments. We combine unsupervised image analysis algorithms with an interactive visualization of the results. Our validation interface allows for each data set to be corrected to 100% accuracy, ensuring that downstream data analysis is accurate and verifiable. Our tool is the first to combine all of these aspects, leveraging the synergies obtained by utilizing validation information from stereo visualization to improve the low level image processing tasks.

Light-Emitting Diode (LED) therapy improves occipital cortex damage by decreasing apoptosis and increasing BDNF-expressing cells in methanol-induced toxicity in rats.

PubMed

Ghanbari, Amir; Ghareghani, Majid; Zibara, Kazem; Delaviz, Hamdallah; Ebadi, Elham; Jahantab, Mohammad Hossein

2017-05-01

Methanol-induced retinal toxicity, frequently associated with elevated free radicals and cell edema, is characterized by progressive retinal ganglion cell (RGC) death and vision loss. Previous studies investigated the effect of photomodulation on RGCs, but not the visual cortex. In this study, the effect of 670nm Light-Emitting Diode (LED) therapy on RGCs and visual cortex recovery was investigated in a seven-day methanol-induced retinal toxicity protocol in rats. Methanol administration showed a reduction in the number of RGCs, loss of neurons (neuronal nuclear antigen, NeuN+), activation of glial fibrillary acidic protein (GFAP+) expressing cells, suppression of brain-derived neurotrophic factor (BDNF+) positive cells, increase in apoptosis (caspase 3+) and enhancement of nitric oxide (NO) release in serum and brain. On the other hand, LED therapy significantly reduced RGC death, in comparison to the methanol group. In addition, the number of BDNF positive cells was significantly higher in the visual cortex of LED-treated group, in comparison to methanol-intoxicated and control groups. Moreover, LED therapy caused a significant decrease in cell death (caspase 3+ cells) and a significant reduction in the NO levels, both in serum and brain tissue, in comparison to methanol-intoxicated rats. Overall, LED therapy demonstrated a number of beneficial effects in decreasing oxidative stress and in functional recovery of RGCs and visual cortex. Our data suggest that LED therapy could be a potential condidate as a non-invasive approach for treatment of retinal damage, which needs further clinicl studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Visualization of channels connecting cells in filamentous nitrogen-fixing cyanobacteria.

PubMed

Omairi-Nasser, Amin; Haselkorn, Robert; Austin, Jotham

2014-07-01

Cyanobacteria, formerly called blue-green algae, are abundant bacteria that carry out green plant photosynthesis, fixing CO2 and generating O2. Many species can also fix N2 when reduced nitrogen sources are scarce. Many studies imply the existence of intracellular communicating channels in filamentous cyanobacteria, in particular, the nitrogen-fixing species. In a species such as Anabaena, growth in nitrogen-depleted medium, in which ∼10% of the cells differentiate into anaerobic factories for nitrogen fixation (heterocysts), requires the transport of amino acids from heterocysts to vegetative cells, and reciprocally, the transport of sugar from vegetative cells to heterocysts. Convincing physical evidence for such channels has been slim. Using improved preservation of structure by high-pressure rapid freezing of samples for electron microscopy, coupled with high-resolution 3D tomography, it has been possible to visualize and measure the dimensions of channels that breach the peptidoglycan between vegetative cells and between heterocysts and vegetative cells. The channels appear to be straight tubes, 21 nm long and 14 nm in diameter for the latter and 12 nm long and 12 nm in diameter for the former.-Omairi-Nasser, A., Haselkorn, R., Austin, J. II. Visualization of channels connecting cells in filamentous nitrogen-fixing cyanobacteria. © FASEB.

The Effects of Phacoemulsification and Intraocular Lens Implantation on Anatomical and Functional Parameters in Patients with Primary Angle Closure: A Prospective Study. (An American Ophthalmological Society Thesis).

PubMed

Traverso, Carlo Enrico; Cutolo, Carlo Alberto

2017-08-01

To investigate the clinical, anatomical, and patient-reported outcomes of phacoemulsification (PE) with intraocular lens implantation performed to treat primary angle closure (PAC) and primary angle-closure glaucoma (PACG). Patients were evaluated at baseline and at 6 months after PE. The examination included visual acuity, intraocular pressure (IOP), visual field, optic nerve head, endothelial cell count (ECC), aqueous depth, and ocular biometric parameters. Patient-reported visual function and health status were assessed. Coprimary outcome measures were IOP changes, angle widening, and patient-reported visual function; secondary outcome measures were visual acuity changes, use of IOP-lowering medications, and complications. Univariate and multivariate analyses were performed to determine the predictors of IOP change. Thirty-nine cases were identified, and postoperative data were analyzed for 59 eyes, 39 with PACG and 20 with PAC. Globally, PE resulted in a mean reduction in IOP of -6.33 mm Hg (95% CI, -8.64 to -4.01, P <.001). Aqueous depth and angle measurements improved ( P <.01), whereas ECC significantly decreased ( P <.001). Both corrected and uncorrected visual acuity improved ( P <.01). The EQ visual analog scale did not change ( P =.16), but VFQ-25 improved ( P <.01). The IOP-lowering effect of PE was greater in the PACG compared to the PAC group ( P =.04). In both groups, preoperative IOP was the most significant predictor of IOP change ( P <.01). No sight-threatening complications were recorded. Our data support the usefulness of PE in lowering the IOP in patients with PAC and PACG. Although PE resulted in several anatomical and patient-reported visual improvements, we observe that a marked decrease in ECC should be carefully weighed before surgery.

Analytical validation of quantitative immunohistochemical assays of tumor infiltrating lymphocyte biomarkers.

PubMed

Singh, U; Cui, Y; Dimaano, N; Mehta, S; Pruitt, S K; Yearley, J; Laterza, O F; Juco, J W; Dogdas, B

2018-06-04

Tumor infiltrating lymphocytes (TIL), especially T-cells, have both prognostic and therapeutic applications. The presence of CD8+ effector T-cells and the ratio of CD8+ cells to FOXP3+ regulatory T-cells have been used as biomarkers of disease prognosis to predict response to various immunotherapies. Blocking the interaction between inhibitory receptors on T-cells and their ligands with therapeutic antibodies including atezolizumab, nivolumab, pembrolizumab and tremelimumab increases the immune response against cancer cells and has shown significant improvement in clinical benefits and survival in several different tumor types. The improved clinical outcome is presumed to be associated with a higher tumor infiltration; therefore, it is thought that more accurate methods for measuring the amount of TIL could assist prognosis and predict treatment response. We have developed and validated quantitative immunohistochemistry (IHC) assays for CD3, CD8 and FOXP3 for immunophenotyping T-lymphocytes in tumor tissue. Various types of formalin fixed, paraffin embedded (FFPE) tumor tissues were immunolabeled with anti-CD3, anti-CD8 and anti-FOXP3 antibodies using an IHC autostainer. The tumor area of stained tissues, including the invasive margin of the tumor, was scored by a pathologist (visual scoring) and by computer-based quantitative image analysis. Two image analysis scores were obtained for the staining of each biomarker: the percent positive cells in the tumor area and positive cells/mm 2 tumor area. Comparison of visual vs. image analysis scoring methods using regression analysis showed high correlation and indicated that quantitative image analysis can be used to score the number of positive cells in IHC stained slides. To demonstrate that the IHC assays produce consistent results in normal daily testing, we evaluated the specificity, sensitivity and reproducibility of the IHC assays using both visual and image analysis scoring methods. We found that CD3, CD8 and FOXP3 IHC assays met the fit-for-purpose analytical acceptance validation criteria and that they can be used to support clinical studies.

Rapid learning in visual cortical networks.

PubMed

Wang, Ye; Dragoi, Valentin

2015-08-26

Although changes in brain activity during learning have been extensively examined at the single neuron level, the coding strategies employed by cell populations remain mysterious. We examined cell populations in macaque area V4 during a rapid form of perceptual learning that emerges within tens of minutes. Multiple single units and LFP responses were recorded as monkeys improved their performance in an image discrimination task. We show that the increase in behavioral performance during learning is predicted by a tight coordination of spike timing with local population activity. More spike-LFP theta synchronization is correlated with higher learning performance, while high-frequency synchronization is unrelated with changes in performance, but these changes were absent once learning had stabilized and stimuli became familiar, or in the absence of learning. These findings reveal a novel mechanism of plasticity in visual cortex by which elevated low-frequency synchronization between individual neurons and local population activity accompanies the improvement in performance during learning.

Surface topography of hairy cell leukemia cells compared to other leukemias as seen by scanning electron microscopy.

PubMed

Polliack, Aaron; Tadmor, Tamar

2011-06-01

This short review deals with the ultrastructural surface architecture of hairy cell leukemia (HCL) compared to other leukemic cells, as seen by scanning electron microscopy (SEM). The development of improved techniques for preparing blood cells for SEM in the 1970s readily enabled these features to be visualized more accurately. This review returns us to the earlier history of SEM, when the surface topography of normal and neoplastic cells was visualized and reported for the first time, in an era before the emergence and use of monoclonal antibodies and flow cytometry, now used routinely to define cells by their immunophenotype. Surface microvilli are characteristic for normal and leukemic lymphoid cells, myelo-monocytic cells lack microvilli and show surface ruffles, while leukemic plasma and myeloma cells and megakaryocytes display large surface blebs. HCL cell surfaces are complex and typically 'hybrid' in nature, displaying both lymphoid and monocytic features with florid ruffles of varying sizes interspersed with clumps of short microvilli cytoplasm. The surface features of other leukemic cells and photomicrographs of immuno-SEM labeling of cells employing antibodies and colloidal gold, reported more than 20 years ago, are shown.

Visualization of phage DNA degradation by a type I CRISPR-Cas system at the single-cell level.

PubMed

Guan, Jingwen; Shi, Xu; Burgos, Roberto; Zeng, Lanying

2017-03-01

The CRISPR-Cas system is a widespread prokaryotic defense system which targets and cleaves invasive nucleic acids, such as plasmids or viruses. So far, a great number of studies have focused on the components and mechanisms of this system, however, a direct visualization of CRISPR-Cas degrading invading DNA in real-time has not yet been studied at the single-cell level. In this study, we fluorescently label phage lambda DNA in vivo , and track the labeled DNA over time to characterize DNA degradation at the single-cell level. At the bulk level, the lysogenization frequency of cells harboring CRISPR plasmids decreases significantly compared to cells with a non-CRISPR control. At the single-cell level, host cells with CRISPR activity are unperturbed by phage infection, maintaining normal growth like uninfected cells, where the efficiency of our anti-lambda CRISPR system is around 26%. During the course of time-lapse movies, the average fluorescence of invasive phage DNA in cells with CRISPR activity, decays more rapidly compared to cells without, and phage DNA is fully degraded by around 44 minutes on average. Moreover, the degradation appears to be independent of cell size or the phage DNA ejection site suggesting that Cas proteins are dispersed in sufficient quantities throughout the cell. With the CRISPR-Cas visualization system we developed, we are able to examine and characterize how a CRISPR system degrades invading phage DNA at the single-cell level. This work provides direct evidence and improves the current understanding on how CRISPR breaks down invading DNA.

Irregular Astigmatism After Corneal Transplantation--Efficacy and Safety of Topography-Guided Treatment.

PubMed

Laíns, Inês; Rosa, Andreia M; Guerra, Marta; Tavares, Cristina; Lobo, Conceição; Silva, Maria F L; Quadrado, Maria J; Murta, Joaquim N

2016-01-01

To analyze the efficacy and safety of topography-guided photorefractive keratectomy (TG-PRK) to treat irregular astigmatism after corneal transplantation. This was a retrospective observational case series. Eyes with irregular astigmatism after penetrating keratoplasty treated with TG-PRK (Allegretto Wave Eye-Q) with the topography-guided customized ablation treatment protocol were included. All treatments had been planned to correct the topographic irregularities, as well as to reduce the refractive error after neutralizing the induced refractive change. Clinical records, treatment plan, and the examinations performed were reviewed and the following data were collected: corrected and uncorrected distance visual acuities; manifest refraction; topographic parameters, and corneal endothelial cell count. We included 31 eyes [30 patients; mean age 45.0 ± 13.4 (SD) years]. At the last postoperative follow-up (mean 9.2 ± 8.2 months), we observed a significant improvement in corrected (P = 0.001) and uncorrected distance visual acuities (P < 0.001). There was a gain of ≥1 uncorrected distance visual acuity line in 96.8% (n = 30) of the eyes. Similarly, the refractive parameters also improved (cylinder P < 0.001; spherical equivalent P = 0.002). At the last visit, 54.8% (n = 17) of the patients presented a spherical equivalent of ±1 D. The 3-mm topographic irregularity also decreased significantly (P < 0.001). There was no significant variation of the corneal endothelial cell count. This is the largest case series of TG-PRK to treat irregular astigmatism in postcorneal transplantation eyes. Our results confirm that TG-PRK is an efficient treatment, associated with significant improvements of both visual acuity and refractive parameters.

Intravital characterization of tumor cell migration in pancreatic cancer

PubMed Central

Beerling, Evelyne; Oosterom, Ilse; Voest, Emile; Lolkema, Martijn; van Rheenen, Jacco

2016-01-01

ABSTRACT Curing pancreatic cancer is difficult as metastases often determine the poor clinical outcome. To gain more insight into the metastatic behavior of pancreatic cancer cells, we characterized migratory cells in primary pancreatic tumors using intravital microscopy. We visualized the migratory behavior of primary tumor cells of a genetically engineered pancreatic cancer mouse model and found that pancreatic tumor cells migrate with a mesenchymal morphology as single individual cells or collectively as a stream of non-cohesive single motile cells. These findings may improve our ability to conceive treatments that block metastatic behavior. PMID:28243522

Biological Characteristics of Fluorescent Superparamagnetic Iron Oxide Labeled Human Dental Pulp Stem Cells

PubMed Central

Li, Ming-wei; Bai, Yu; Guo, Hui-hui

2017-01-01

Tracking transplanted stem cells is necessary to clarify cellular properties and improve transplantation success. In this study, we investigate the effects of fluorescent superparamagnetic iron oxide particles (SPIO) (Molday ION Rhodamine-B™, MIRB) on biological properties of human dental pulp stem cells (hDPSCs) and monitor hDPSCs in vitro and in vivo using magnetic resonance imaging (MRI). Morphological analysis showed that intracellular MIRB particles were distributed in the cytoplasm surrounding the nuclei of hDPSCs. 12.5–100 μg/mL MIRB all resulted in 100% labeling efficiency. MTT showed that 12.5–50 μg/mL MIRB could promote cell proliferation and MIRB over 100 μg/mL exhibited toxic effect on hDPSCs. In vitro MRI showed that 1 × 106 cells labeled with various concentrations of MIRB (12.5–100 μg/mL) could be visualized. In vivo MRI showed that transplanted cells could be clearly visualized up to 60 days after transplantation. These results suggest that 12.5–50 μg/mL MIRB is a safe range for labeling hDPSCs. MIRB labeled hDPSCs cell can be visualized by MRI in vitro and in vivo. These data demonstrate that MIRB is a promising candidate for hDPSCs tracking in hDPSCs based dental pulp regeneration therapy. PMID:28298928

Learning and Prediction of Slip from Visual Information

NASA Technical Reports Server (NTRS)

Angelova, Anelia; Matthies, Larry; Helmick, Daniel; Perona, Pietro

2007-01-01

This paper presents an approach for slip prediction from a distance for wheeled ground robots using visual information as input. Large amounts of slippage which can occur on certain surfaces, such as sandy slopes, will negatively affect rover mobility. Therefore, obtaining information about slip before entering such terrain can be very useful for better planning and avoiding these areas. To address this problem, terrain appearance and geometry information about map cells are correlated to the slip measured by the rover while traversing each cell. This relationship is learned from previous experience, so slip can be predicted remotely from visual information only. The proposed method consists of terrain type recognition and nonlinear regression modeling. The method has been implemented and tested offline on several off-road terrains including: soil, sand, gravel, and woodchips. The final slip prediction error is about 20%. The system is intended for improved navigation on steep slopes and rough terrain for Mars rovers.

[Large vessel vasculitides].

PubMed

Morović-Vergles, Jadranka; Puksić, Silva; Gracanin, Ana Gudelj

2013-01-01

Large vessel vasculitis includes Giant cell arteritis and Takayasu arteritis. Giant cell arteritis is the most common form of vasculitis affect patients aged 50 years or over. The diagnosis should be considered in older patients who present with new onset of headache, visual disturbance, polymyalgia rheumatica and/or fever unknown cause. Glucocorticoides remain the cornerstone of therapy. Takayasu arteritis is a chronic panarteritis of the aorta ant its major branches presenting commonly in young ages. Although all large arteries can be affected, the aorta, subclavian and carotid arteries are most commonly involved. The most common symptoms included upper extremity claudication, hypertension, pain over the carotid arteries (carotidynia), dizziness and visual disturbances. Early diagnosis and treatment has improved the outcome in patients with TA.

CV2/CRMP5-antibody-related Paraneoplastic Optic Neuropathy Associated with Small-cell Lung Cancer.

PubMed

Nakajima, Masanori; Uchibori, Ayumi; Ogawa, Yuki; Miyazaki, Tai; Ichikawa, Yaeko; Kaneko, Kimihiko; Takahashi, Toshiyuki; Nakashima, Ichiro; Shiraishi, Hirokazu; Motomura, Masakatsu; Chiba, Atsuro

2018-06-01

A 61-year-old woman who had smoked for 41 years developed subacute dizziness, ataxic gait, opsoclonus, and right visual impairment. She had right optic disc swelling and optic nerve gadolinium enhancement on magnetic resonance imaging. She had small-cell lung cancer (SCLC), with CV2/collapsin response mediator protein (CRMP) 5 and HuD antibodies in her serum and cerebrospinal fluid. She was diagnosed with paraneoplastic optic neuropathy (PON) accompanied by paraneoplastic opsoclonus-ataxia syndrome. Her symptoms improved after removing the SCLC. Classical PON is rare in Japan. We recommend assaying for CV2/CRMP5 antibodies and searching for cancer in elderly patients with subacute painless visual impairment.

3D visualization of subcellular structures of Schizosaccharomyces pombe by hard X-ray tomography.

PubMed

Yang, Y; Li, W; Liu, G; Zhang, X; Chen, J; Wu, W; Guan, Y; Xiong, Y; Tian, Y; Wu, Z

2010-10-01

Cellular structures of the fission yeast, Schizosaccharomyces pombe, were examined by using hard X-ray tomography. Since cells are nearly transparent to hard X-rays, Zernike phase contrast and heavy metal staining were introduced to improve image contrast. Through using such methods, images taken at 8 keV displayed sufficient contrast for observing cellular structures. The cell wall, the intracellular organelles and the entire structural organization of the whole cells were visualized in three-dimensional at a resolution better than 100 nm. Comparison between phase contrast and absorption contrast was also made, indicating the obvious advantage of phase contrast for cellular imaging at this energy. Our results demonstrate that hard X-ray tomography with Zernike phase contrast is suitable for cellular imaging. Its unique abilities make it have potential to become a useful tool for revealing structural information from cells, especially thick eukaryotic cells. © 2010 The Authors Journal compilation © 2010 The Royal Microscopical Society.

Outcome of cataract surgery following simple limbal epithelial transplantation for lime injury-induced limbal stem cell deficiency

PubMed Central

Nair, Dhanyasree

2015-01-01

A 19-year-old woman presented to us after being diagnosed elsewhere with right eye total limbal stem cell deficiency resulting from a lime burn. She was advised to undergo limbal stem cell transplantation, but failed to immediately do so. Two years later, she underwent cultivated limbal epithelial transplantation (CLET). As she had severe loss of vision with persisting conjunctival nodule and symblepharon 2 years following surgery, an impression of failed CLET was formed. Subsequently, simple limbal epithelial transplantation (SLET) was performed. Nine months later, she developed a cataract in her right eye; the cataract was extracted and posterior chamber intraocular lens implanted. The unaided visual acuity improved from light perception at presentation to 20/60 at 1-week postoperatively. At 5 months follow-up, the patient continued to maintain 20/60 visual acuity in her right eye. This case describes the outcome of cataract surgery following SLET, emphasising the need to perform cataract surgery in complicated cataracts for a better visual prognosis. PMID:26698204

The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal Amacrine Cell of the Rabbit Retina.

PubMed

Murphy-Baum, Benjamin L; Taylor, W Rowland

2015-09-30

Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene. Copyright © 2015 the authors 0270-6474/15/3513336-15$15.00/0.

Daily visual stimulation in the critical period enhances multiple aspects of vision through BDNF-mediated pathways in the mouse retina

PubMed Central

Mui, Amanda M.; Yang, Victoria; Aung, Moe H.; Fu, Jieming; Adekunle, Adewumi N.; Prall, Brian C.; Sidhu, Curran S.; Park, Han na; Boatright, Jeffrey H.; Iuvone, P. Michael

2018-01-01

Visual experience during the critical period modulates visual development such that deprivation causes visual impairments while stimulation induces enhancements. This study aimed to determine whether visual stimulation in the form of daily optomotor response (OMR) testing during the mouse critical period (1) improves aspects of visual function, (2) involves retinal mechanisms and (3) is mediated by brain derived neurotrophic factor (BDNF) and dopamine (DA) signaling pathways. We tested spatial frequency thresholds in C57BL/6J mice daily from postnatal days 16 to 23 (P16 to P23) using OMR testing. Daily OMR-treated mice were compared to littermate controls that were placed in the OMR chamber without moving gratings. Contrast sensitivity thresholds, electroretinograms (ERGs), visual evoked potentials, and pattern ERGs were acquired at P21. To determine the role of BDNF signaling, a TrkB receptor antagonist (ANA-12) was systemically injected 2 hours prior to OMR testing in another cohort of mice. BDNF immunohistochemistry was performed on retina and brain sections. Retinal DA levels were measured using high-performance liquid chromatography. Daily OMR testing enhanced spatial frequency thresholds and contrast sensitivity compared to controls. OMR-treated mice also had improved rod-driven ERG oscillatory potential response times, greater BDNF immunoreactivity in the retinal ganglion cell layer, and increased retinal DA content compared to controls. VEPs and pattern ERGs were unchanged. Systemic delivery of ANA-12 attenuated OMR-induced visual enhancements. Daily OMR testing during the critical period leads to general visual function improvements accompanied by increased DA and BDNF in the retina, with this process being requisitely mediated by TrkB activation. These results suggest that novel combination therapies involving visual stimulation and using both behavioral and molecular approaches may benefit degenerative retinal diseases or amblyopia. PMID:29408880

Visual analysis of orthokeratology on myopia reduction for aviators

NASA Astrophysics Data System (ADS)

Mitsui, Iwane

2005-04-01

Ortho-K was indicated for sixty eyes of thirty aviators, twenty-one pilots and nine flight attendants, with age of 34.5 on the average. Uncorrected visual acuity (UCVA) was originally 20/30 or worse in all cases. The mean spherical equivalent (SE) was -3.69 Diopters (D). The same ophthalmologist designed full costumed reverse geometry Advanced Orthokeratology lenses for each patient. All the patients were followed at least two years wearing of Advanced Ortho-K lenses. The follow up examinations on auto-refraction, auto-keratometry, uncorrected and corrected visual acuity, intra-ocular pressure, corneal endothelial cells, corneal thickness and curve, and corneal shape were performed in the morning, 10am to 12am. 94% of the patients improved in UCVA up to 20/20 or better, 87% of them improved up to 20/15 or better, and 67% of them improved up to 20/10. The mean SEs improved to -1.90+/-1.00D during six months, -1.49+/-1.03D during one year, and -0.73+/-0.94D during two years. Astigmatism slightly increased by 0.38D on the average, however, it did not cause any serious problems for aviation tasks even during night. Intraocular pressure did not increase and corneal endothelial cells did not decrease. Other ophthalmologic examinations showed normal conditions and any complications were not observed throughout the period. Advanced Ortho-K was evaluated to be safe and effective enough for also aviators with myopia. It can be recommended one of the options of reduction of myopia for aviators. Evaluations on night vision and night glare are planned for further studies.

Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats.

PubMed

Lund, Raymond D; Wang, Shaomei; Klimanskaya, Irina; Holmes, Toby; Ramos-Kelsey, Rebeca; Lu, Bin; Girman, Sergej; Bischoff, N; Sauvé, Yves; Lanza, Robert

2006-01-01

Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement tissue for human clinical studies. An early potential application of this technology is the use of retinal pigment epithelium (RPE) for the treatment of retinal degenerative diseases such as macular degeneration. Here we show the reproducible generation of RPE (67 passageable cultures established from 18 different hES cell lines); batches of RPE derived from NIH-approved hES cells (H9) were tested and shown capable of extensive photoreceptor rescue in an animal model of retinal disease, the Royal College of Surgeons (RCS) rat, in which photoreceptor loss is caused by a defect in the adjacent retinal pigment epithelium. Improvement in visual performance was 100% over untreated controls (spatial acuity was approximately 70% that of normal nondystrophic rats) without evidence of untoward pathology. The use of somatic cell nuclear transfer (SCNT) and/or the creation of banks of reduced complexity human leucocyte antigen (HLA) hES-RPE lines could minimize or eliminate the need for immunosuppressive drugs and/or immunomodulatory protocols.

Endothelial keratoplasty with infant donor tissue

PubMed Central

Kobayashi, Akira; Yokogawa, Hideaki; Yamazaki, Natsuko; Masaki, Toshinori; Sugiyama, Kazuhisa

2014-01-01

Here we report a case of endothelial keratoplasty with infant donor tissue obtained after brain death. A 52-year-old man with endothelial dysfunction of unknown cause in the right eye underwent non-Descemet stripping automated endothelial keratoplasty (nDSAEK) with tissue from an infant donor (2 years). Intraoperative and postoperative complications were recorded. Best corrected visual acuity and donor central endothelial cell density were recorded preoperatively and postoperatively. Infant donor tissue preparation with a microkeratome set at 300 μm was successful; the donor tissue was extremely elastic and soft compared with adult tissue. The central endothelial cell density of the infant donor tissue was as high as 4,291 cells/mm2. No complications were observed during donor tissue (8.0 mm in diameter) insertion with the double-glide technique (Busin glide with intraocular lens sheet glide) or any of the other procedures. Best corrected visual acuity improved from 1.7 logMAR (logarithm of the minimum angle of resolution; 0.02 decimal visual acuity) preoperatively to 0.2 logMAR (0.6) after 6 months and 0.1 logMAR (0.8) after 1 year. The central endothelial cell density after 6 months was 4,098 cells/mm2 (representing a 4.5% cell loss from preoperative donor cell measurements), and the central endothelial cell density after 1 year was 4,032 cells/mm2 (6.0% decrease). Infant donor tissue may be preferably used for DSAEK/nDASEK, since it may not be suitable for penetrating keratoplasty or Descemet membrane endothelial keratoplasty. PMID:25246761

Sample to answer visualization pipeline for low-cost point-of-care blood cell counting

NASA Astrophysics Data System (ADS)

Smith, Suzanne; Naidoo, Thegaran; Davies, Emlyn; Fourie, Louis; Nxumalo, Zandile; Swart, Hein; Marais, Philip; Land, Kevin; Roux, Pieter

2015-03-01

We present a visualization pipeline from sample to answer for point-of-care blood cell counting applications. Effective and low-cost point-of-care medical diagnostic tests provide developing countries and rural communities with accessible healthcare solutions [1], and can be particularly beneficial for blood cell count tests, which are often the starting point in the process of diagnosing a patient [2]. The initial focus of this work is on total white and red blood cell counts, using a microfluidic cartridge [3] for sample processing. Analysis of the processed samples has been implemented by means of two main optical visualization systems developed in-house: 1) a fluidic operation analysis system using high speed video data to determine volumes, mixing efficiency and flow rates, and 2) a microscopy analysis system to investigate homogeneity and concentration of blood cells. Fluidic parameters were derived from the optical flow [4] as well as color-based segmentation of the different fluids using a hue-saturation-value (HSV) color space. Cell count estimates were obtained using automated microscopy analysis and were compared to a widely accepted manual method for cell counting using a hemocytometer [5]. The results using the first iteration microfluidic device [3] showed that the most simple - and thus low-cost - approach for microfluidic component implementation was not adequate as compared to techniques based on manual cell counting principles. An improved microfluidic design has been developed to incorporate enhanced mixing and metering components, which together with this work provides the foundation on which to successfully implement automated, rapid and low-cost blood cell counting tests.

Phototaxis and the origin of visual eyes

PubMed Central

Randel, Nadine

2016-01-01

Vision allows animals to detect spatial differences in environmental light levels. High-resolution image-forming eyes evolved from low-resolution eyes via increases in photoreceptor cell number, improvements in optics and changes in the neural circuits that process spatially resolved photoreceptor input. However, the evolutionary origins of the first low-resolution visual systems have been unclear. We propose that the lowest resolving (two-pixel) visual systems could initially have functioned in visual phototaxis. During visual phototaxis, such elementary visual systems compare light on either side of the body to regulate phototactic turns. Another, even simpler and non-visual strategy is characteristic of helical phototaxis, mediated by sensory–motor eyespots. The recent mapping of the complete neural circuitry (connectome) of an elementary visual system in the larva of the annelid Platynereis dumerilii sheds new light on the possible paths from non-visual to visual phototaxis and to image-forming vision. We outline an evolutionary scenario focusing on the neuronal circuitry to account for these transitions. We also present a comprehensive review of the structure of phototactic eyes in invertebrate larvae and assign them to the non-visual and visual categories. We propose that non-visual systems may have preceded visual phototactic systems in evolution that in turn may have repeatedly served as intermediates during the evolution of image-forming eyes. PMID:26598725

Differences in Visual-Spatial Input May Underlie Different Compression Properties of Firing Fields for Grid Cell Modules in Medial Entorhinal Cortex

PubMed Central

Raudies, Florian; Hasselmo, Michael E.

2015-01-01

Firing fields of grid cells in medial entorhinal cortex show compression or expansion after manipulations of the location of environmental barriers. This compression or expansion could be selective for individual grid cell modules with particular properties of spatial scaling. We present a model for differences in the response of modules to barrier location that arise from different mechanisms for the influence of visual features on the computation of location that drives grid cell firing patterns. These differences could arise from differences in the position of visual features within the visual field. When location was computed from the movement of visual features on the ground plane (optic flow) in the ventral visual field, this resulted in grid cell spatial firing that was not sensitive to barrier location in modules modeled with small spacing between grid cell firing fields. In contrast, when location was computed from static visual features on walls of barriers, i.e. in the more dorsal visual field, this resulted in grid cell spatial firing that compressed or expanded based on the barrier locations in modules modeled with large spacing between grid cell firing fields. This indicates that different grid cell modules might have differential properties for computing location based on visual cues, or the spatial radius of sensitivity to visual cues might differ between modules. PMID:26584432

Cell Phones, Tablets, and Other Mobile Technology for Users with Visual Impairments

MedlinePlus

... Visual Impairments Cell Phones, Tablets, and Other Mobile Technology for Users with Visual Impairments The Mobile Revolution ... 223 Likes) Cell Phones, Tablets, and Other Mobile Technology Touchscreen Smartphone Accessibility for People with Visual Impairments ...

Retinal stimulation strategies to restore vision: Fundamentals and systems.

PubMed

Yue, Lan; Weiland, James D; Roska, Botond; Humayun, Mark S

2016-07-01

Retinal degeneration, a leading cause of blindness worldwide, is primarily characterized by the dysfunctional/degenerated photoreceptors that impair the ability of the retina to detect light. Our group and others have shown that bioelectronic retinal implants restore useful visual input to those who have been blind for decades. This unprecedented approach of restoring sight demonstrates that patients can adapt to new visual input, and thereby opens up opportunities to not only improve this technology but also develop alternative retinal stimulation approaches. These future improvements or new technologies could have the potential of selectively stimulating specific cell classes in the inner retina, leading to improved visual resolution and color vision. In this review we will detail the progress of bioelectronic retinal implants and future devices in this genre as well as discuss other technologies such as optogenetics, chemical photoswitches, and ultrasound stimulation. We will discuss the principles, biological aspects, technology development, current status, clinical outcomes/prospects, and challenges for each approach. The review will cover functional imaging documented cortical responses to retinal stimulation in blind patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Visualizing Without Vision at the Microscale: Students With Visual Impairments Explore Cells With Touch

NASA Astrophysics Data System (ADS)

Jones, M. Gail; Minogue, James; Oppewal, Tom; Cook, Michelle P.; Broadwell, Bethany

2006-12-01

Science instruction is typically highly dependent on visual representations of scientific concepts that are communicated through textbooks, teacher presentations, and computer-based multimedia materials. Little is known about how students with visual impairments access and interpret these types of visually-dependent instructional materials. This study explored the efficacy of new haptic (simulated tactile feedback and kinesthetics) instructional technology for teaching cell morphology and function to middle and high school students with visual impairments. The study examined students' prior experiences learning about the cell and cell functions in classroom instruction, as well as how haptic feedback technology impacted students' awareness of the 3-D nature of an animal cell, the morphology and function of cell organelles, and students' interest in the haptic technology as an instructional tool. Twenty-one students with visual impairment participated in the study. Students explored a tactile model of the cell with a haptic point probe that allowed them to feel the cell and its organelles. Results showed that students made significant gains in their ability to identify cell organelles and found the technology to be highly interesting as an instructional tool. The need for additional adaptive technology for students with visual impairments is discussed.

Novel full-spectral flow cytometry with multiple spectrally-adjacent fluorescent proteins and fluorochromes and visualization of in vivo cellular movement.

PubMed

Futamura, Koji; Sekino, Masashi; Hata, Akihiro; Ikebuchi, Ryoyo; Nakanishi, Yasutaka; Egawa, Gyohei; Kabashima, Kenji; Watanabe, Takeshi; Furuki, Motohiro; Tomura, Michio

2015-09-01

Flow cytometric analysis with multicolor fluoroprobes is an essential method for detecting biological signatures of cells. Here, we present a new full-spectral flow cytometer (spectral-FCM). Unlike conventional flow cytometer, this spectral-FCM acquires the emitted fluorescence for all probes across the full-spectrum from each cell with 32 channels sequential PMT unit after dispersion with prism, and extracts the signals of each fluoroprobe based on the spectral shape of each fluoroprobe using unique algorithm in high speed, high sensitive, accurate, automatic and real-time. The spectral-FCM detects the continuous changes in emission spectra from green to red of the photoconvertible protein, KikGR with high-spectral resolution and separates spectrally-adjacent fluoroprobes, such as FITC (Emission peak (Em) 519 nm) and EGFP (Em 507 nm). Moreover, the spectral-FCM can measure and subtract autofluorescence of each cell providing increased signal-to-noise ratios and improved resolution of dim samples, which leads to a transformative technology for investigation of single cell state and function. These advances make it possible to perform 11-color fluorescence analysis to visualize movement of multilinage immune cells by using KikGR-expressing mice. Thus, the novel spectral flow cytometry improves the combinational use of spectrally-adjacent various FPs and multicolor fluorochromes in metabolically active cell for the investigation of not only the immune system but also other research and clinical fields of use. © 2015 International Society for Advancement of Cytometry.

Ocular vascular occlusive disorders: Natural history of visual outcome☆

PubMed Central

Hayreh, Sohan Singh

2014-01-01

Ocular vascular occlusive disorders collectively constitute the most common cause of visual disability. Before a disease can be managed, it is essential to understand its natural history, so as to be able to assess the likely effectiveness of any intervention. I investigated natural history of visual outcome in prospective studies of 386 eyes with non-arteritic anterior ischemic optic neuropathy (NA-AION), 16 eyes with non-arteritic posterior ischemic optic neuropathy, 697 eyes with central retinal vein occlusion (CRVO), 67 eyes with hemi-CRVO (HCRVO), 216 eyes with branch retinal vein occlusion (BRVO), 260 eyes with central retinal artery occlusion (CRAO), 151 eyes with branch retinal artery occlusion (BRAO) and 61 eyes with cilioretinal artery occlusion (CLRAO). My studies have shown that every one of these disorders consists of multiple distinct clinical sub-categories with different visual findings. When an ocular vascular occlusive disorder is caused by giant cell arteritis, which is an ophthalmic emergency, it would be unethical to do a natural history study of visual outcome in them, because in this case early diagnosis and immediate, intensive high-dose steroid therapy is essential to prevent any further visual loss, not only in the involved eye but also in the fellow, normal eye. In NA-AION in eyes seen ≤2 weeks after the onset, visual acuity (VA) improved in 41% of those with VA 20/70 or worse, and visual field (VF) improved in 26% of those with moderate to severe VF defect. In non-ischemic CRVO eyes with VA 20/70 or worse, VA improved in 47% and in ischemic CRVO in 23%; moderate to severe VF defect improved in 79% in non-ischemic CRVO and in 27% in ischemic CRVO. In HCRVO, overall findings demonstrated that initial VA and VF defect and the final visual outcome were different in non-ischemic from ischemic HCRVO – much better in the former than the latter. In major BRVO, in eyes with initial VA of 20/70 or worse, VA improved in 69%, and moderate to severe VF defect improved in 52%. In macular BRVO with 20/70 or worse initial VA, it improved in 53%, and initial minimal-mild VF defect was stable or improved in 85%. In various types of CRAO there are significant differences in both initial and final VA and VF defects. In CRAO eyes seen within 7 days of onset and initial VA of counting fingers or worse, VA improved in 82% with transient non-arteritic CRAO, 67% with non-arteritic CRAO with cilioretinal artery sparing, 22% with non-arteritic CRAO. Central VF improved in 39% of transient non-arteritic CRAO, 25% of non-arteritic CRAO with cilioretinal artery sparing and 21% of non-arteritic CRAO. Peripheral VF improved in non-arteritic CRAO in 39% and in transient non-arteritic CRAO in 39%. In transient CRAO, finally peripheral VFs were normal in 93%. In non-arteritic CRAO eyes initially 22% had normal peripheral VF and in the rest it improved in 39%. Final VA of 20/40 or better was seen in 89% of permanent BRAO, and in 100% of transient BRAO and non-arteritic CLRAO. In permanent BRAO eyes, among those seen within 7 days of onset, central VF defect improved in 47% and peripheral VF in 52%, and in transient BRAO central and peripheral VFs were normal at follow-up. My studies showed that AION, CRVO, BRVO, CRAO and BRAO, each consist of multiple distinct clinical sub-categories with different visual outcome. Contrary to the prevalent impression, these studies on the natural history of visual outcome have shown that there is a statistically significant spontaneous visual improvement in each category. The factors which influence the visual outcome in various ocular vascular occlusive disorders are discussed. PMID:24769221

Femtosecond laser correction of presbyopia (INTRACOR) in emmetropes using a modified pattern.

PubMed

Thomas, Bettina C; Fitting, Anna; Auffarth, Gerd U; Holzer, Mike P

2012-12-01

To evaluate functional results and corneal changes after femtosecond laser correction of presbyopia (INTRACOR, Technolas Perfect Vision GmbH) in emmetropes using a modified treatment pattern over a 12-month period. Twenty eyes from 20 emmetropic patients were treated with a modified intrastromal INTRACOR pattern consisting of 5 central rings and 8 radial cuts in a prospective, nonrandomized, uncontrolled, open, single-center, clinical study. Refraction, visual acuity, endothelial cell density, corneal pachymetry, total corneal power, and stray light were evaluated preoperatively and 1 (except endothelial cell density and stray light), 3, 6, and 12 months postoperatively. Patients filled out a subjective questionnaire at 12 months postoperatively. Comparison of preoperative versus 12-month postoperative median values revealed a significant improvement in uncorrected near visual acuity (UNVA) from 0.60 (20/80) to 0.10 logMAR (20/25) (P<.0001) and a significant decrease in corrected distance visual acuity (CDVA) from -0.10 (20/16) to 0.00 logMAR (20/20), which equals a median loss of one line (P=.0005). Fifteen percent of patients lost two lines of CDVA in the treated eye. Subjective spherical equivalent refraction remained unchanged at 0.00 diopters (D) (P=.194). After INTRACOR treatment, significant corneal steepening of 1.40 D and midperipheral flattening of 0.50 D occurred (both P<.0001). Corneal pachymetry at the thinnest point and endothelial cell density did not change significantly (P=.829 and P=.058, respectively). After 12 months, the modified INTRACOR pattern improved UNVA in emmetropic patients without inducing a myopic shift or significant changes in endothelial cell density or pachymetry. Copyright 2012, SLACK Incorporated.

A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant.

PubMed

Ronald, John A; Kim, Byung-Su; Gowrishankar, Gayatri; Namavari, Mohammad; Alam, Israt S; D'Souza, Aloma; Nishikii, Hidekazu; Chuang, Hui-Yen; Ilovich, Ohad; Lin, Chih-Feng; Reeves, Robert; Shuhendler, Adam; Hoehne, Aileen; Chan, Carmel T; Baker, Jeanette; Yaghoubi, Shahriar S; VanBrocklin, Henry F; Hawkins, Randall; Franc, Benjamin L; Jivan, Salma; Slater, James B; Verdin, Emily F; Gao, Kenneth T; Benjamin, Jonathan; Negrin, Robert; Gambhir, Sanjiv Sam

2017-06-01

A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages. Here, we show that a novel PET radiotracer, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways preferentially accumulates in activated primary T cells. [18F]F-AraG PET imaging of a murine aGVHD model enabled visualization of secondary lymphoid organs harboring activated donor T cells prior to clinical symptoms. Tracer biodistribution in healthy humans showed favorable kinetics. This new PET strategy has great potential for early aGVHD diagnosis, enabling timely treatments and improved patient outcomes. [18F]F-AraG may be useful for imaging activated T cells in various biomedical applications. Cancer Res; 77(11); 2893-902. ©2017 AACR . ©2017 American Association for Cancer Research.

High resolution imaging of intracellular oxygen concentration by phosphorescence lifetime

PubMed Central

Kurokawa, Hiromi; Ito, Hidehiro; Inoue, Mai; Tabata, Kenji; Sato, Yoshifumi; Yamagata, Kazuya; Kizaka-Kondoh, Shinae; Kadonosono, Tetsuya; Yano, Shigenobu; Inoue, Masahiro; Kamachi, Toshiaki

2015-01-01

Optical methods using phosphorescence quenching by oxygen are suitable for sequential monitoring and non-invasive measurements for oxygen concentration (OC) imaging within cells. Phosphorescence intensity measurement is widely used with phosphorescent dyes. These dyes are ubiquitously but heterogeneously distributed inside the whole cell. The distribution of phosphorescent dye is a major disadvantage in phosphorescence intensity measurement. We established OC imaging system for a single cell using phosphorescence lifetime and a laser scanning confocal microscope. This system had improved spatial resolution and reduced the measurement time with the high repetition rate of the laser. By the combination of ubiquitously distributed phosphorescent dye with this lifetime imaging microscope, we can visualize the OC inside the whole cell and spheroid. This system uses reversible phosphorescence quenching by oxygen, so it can measure successive OC changes from normoxia to anoxia. Lower regions of OC inside the cell colocalized with mitochondria. The time-dependent OC change in an insulin-producing cell line MIN6 by the glucose stimulation was successfully visualized. Assessing the detailed distribution and dynamics of OC inside cells achieved by the presented system will be useful to understanding a physiological and pathological oxygen metabolism. PMID:26065366

[Retrospective analysis of the effect of vinpocetine infusion in ophthalmologic disorders].

PubMed

Végh, Sarolta; Szikszay, Erzsébet; Bönöczk, Péter; Cserjés, Zsuzsanna; Kiss, Gyöngyvér

2006-12-10

Retrospective analysis of the effect of vinpocetine infusion in ophthalmologic disorders. The authors retrospectively examined the effect of vinpocetine infusion on various ophthalmological disorders. Based on the data of 280 patients they concluded that vinpocetine infusion has beneficial effects in numerous ophthalmologic disorders of vision and visual field. There was a clear difference regarding the response to treatment. Best results were achieved in diseases characterized by sclerosis, hypertonia and macular degeneration. The improvement was modest or progression was slowed in patients with nervus opticus ischaemia, glaucoma and myopia. These results are in accordance with the literature data. The beneficial effect of vinpocetine can be explained by the fact that the vessels of the eye are in direct connection with the cerebral circulation and hereby the circulation improving effect of vinpocetine could be effective. The neuronal effects of vinpocetine could also play a role at least in two ways. On the one hand by the direct effect exerted on the cells of retina (these cells are related to the neurons), and on the other hand by the improvement of the circulation and metabolism of the secondary visual cortex found in the occipital lobe (this effect is proved by PET studies).

Recombination imaging of III-V solar cells

NASA Technical Reports Server (NTRS)

Virshup, G. F.

1987-01-01

An imaging technique based on the radiative recombination of minority carriers in forward-biased solar cells has been developed for characterization of III-V solar cells. When used in mapping whole wafers, it has helped identify three independent loss mechanisms (broken grid lines, shorting defects, and direct-to-indirect bandgap transitions), all of which resulted in lower efficiencies. The imaging has also led to improvements in processing techniques to reduce the occurrence of broken gridlines as well as surface defects. The ability to visualize current mechanisms in solar cells is an intuitive tool which is powerful in its simplicity.

IMPROVED METHODS FOR HEPATITIS A VIRUS AND ROTAVIRUS CONCENTRATION AND DETECTION IN RECREATIONAL, RAW POTABLE, AND FINISHED WATERS

EPA Science Inventory

The report contains procedures for detecting rotaviruses based upon an immunofluorescence test using a monoclonal antibody and fluorescein-isothiocyanate-conjugated antibody staining method to visualize virus-infected cells. Also contained in the report are test methods for detec...

From grid cells and visual place cells to multimodal place cell: a new robotic architecture

PubMed Central

Jauffret, Adrien; Cuperlier, Nicolas; Gaussier, Philippe

2015-01-01

In the present study, a new architecture for the generation of grid cells (GC) was implemented on a real robot. In order to test this model a simple place cell (PC) model merging visual PC activity and GC was developed. GC were first built from a simple “several to one” projection (similar to a modulo operation) performed on a neural field coding for path integration (PI). Robotics experiments raised several practical and theoretical issues. To limit the important angular drift of PI, head direction information was introduced in addition to the robot proprioceptive signal coming from the wheel rotation. Next, a simple associative learning between visual place cells and the neural field coding for the PI has been used to recalibrate the PI and to limit its drift. Finally, the parameters controlling the shape of the PC built from the GC have been studied. Increasing the number of GC obviously improves the shape of the resulting place field. Yet, other parameters such as the discretization factor of PI or the lateral interactions between GC can have an important impact on the place field quality and avoid the need of a very large number of GC. In conclusion, our results show our GC model based on the compression of PI is congruent with neurobiological studies made on rodent. GC firing patterns can be the result of a modulo transformation of PI information. We argue that such a transformation may be a general property of the connectivity from the cortex to the entorhinal cortex. Our model predicts that the effect of similar transformations on other kinds of sensory information (visual, tactile, auditory, etc…) in the entorhinal cortex should be observed. Consequently, a given EC cell should react to non-contiguous input configurations in non-spatial conditions according to the projection from its different inputs. PMID:25904862

Fluorescence In situ Hybridization: Cell-Based Genetic Diagnostic and Research Applications.

PubMed

Cui, Chenghua; Shu, Wei; Li, Peining

2016-01-01

Fluorescence in situ hybridization (FISH) is a macromolecule recognition technology based on the complementary nature of DNA or DNA/RNA double strands. Selected DNA strands incorporated with fluorophore-coupled nucleotides can be used as probes to hybridize onto the complementary sequences in tested cells and tissues and then visualized through a fluorescence microscope or an imaging system. This technology was initially developed as a physical mapping tool to delineate genes within chromosomes. Its high analytical resolution to a single gene level and high sensitivity and specificity enabled an immediate application for genetic diagnosis of constitutional common aneuploidies, microdeletion/microduplication syndromes, and subtelomeric rearrangements. FISH tests using panels of gene-specific probes for somatic recurrent losses, gains, and translocations have been routinely applied for hematologic and solid tumors and are one of the fastest-growing areas in cancer diagnosis. FISH has also been used to detect infectious microbias and parasites like malaria in human blood cells. Recent advances in FISH technology involve various methods for improving probe labeling efficiency and the use of super resolution imaging systems for direct visualization of intra-nuclear chromosomal organization and profiling of RNA transcription in single cells. Cas9-mediated FISH (CASFISH) allowed in situ labeling of repetitive sequences and single-copy sequences without the disruption of nuclear genomic organization in fixed or living cells. Using oligopaint-FISH and super-resolution imaging enabled in situ visualization of chromosome haplotypes from differentially specified single-nucleotide polymorphism loci. Single molecule RNA FISH (smRNA-FISH) using combinatorial labeling or sequential barcoding by multiple round of hybridization were applied to measure mRNA expression of multiple genes within single cells. Research applications of these single molecule single cells DNA and RNA FISH techniques have visualized intra-nuclear genomic structure and sub-cellular transcriptional dynamics of many genes and revealed their functions in various biological processes.

Recent advances in targeted endoscopic imaging: Early detection of gastrointestinal neoplasms

PubMed Central

Kwon, Yong-Soo; Cho, Young-Seok; Yoon, Tae-Jong; Kim, Ho-Shik; Choi, Myung-Gyu

2012-01-01

Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy. This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells. Molecular imaging has several advantages including minimal damage to tissues, repetitive visualization, and utility for conducting quantitative analyses. Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible. Molecular imaging during gastrointestinal endoscopy requires the development of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio. Additionally, a high-resolution endoscope with an accurate wide-field viewing capability must be developed. Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer. PMID:22442742

Complex inhibitory microcircuitry regulates retinal signaling near visual threshold

PubMed Central

Grimes, William N.; Zhang, Jun; Tian, Hua; Graydon, Cole W.; Hoon, Mrinalini; Rieke, Fred

2015-01-01

Neuronal microcircuits, small, localized signaling motifs involving two or more neurons, underlie signal processing and computation in the brain. Compartmentalized signaling within a neuron may enable it to participate in multiple, independent microcircuits. Each A17 amacrine cell in the mammalian retina contains within its dendrites hundreds of synaptic feedback microcircuits that operate independently to modulate feedforward signaling in the inner retina. Each of these microcircuits comprises a small (<1 μm) synaptic varicosity that typically receives one excitatory synapse from a presynaptic rod bipolar cell (RBC) and returns two reciprocal inhibitory synapses back onto the same RBC terminal. Feedback inhibition from the A17 sculpts the feedforward signal from the RBC to the AII, a critical component of the circuitry mediating night vision. Here, we show that the two inhibitory synapses from the A17 to the RBC express kinetically distinct populations of GABA receptors: rapidly activating GABAARs are enriched at one synapse while more slowly activating GABACRs are enriched at the other. Anatomical and electrophysiological data suggest that macromolecular complexes of voltage-gated (Cav) channels and Ca2+-activated K+ channels help to regulate GABA release from A17 varicosities and limit GABACR activation under certain conditions. Finally, we find that selective elimination of A17-mediated feedback inhibition reduces the signal to noise ratio of responses to dim flashes recorded in the feedforward pathway (i.e., the AII amacrine cell). We conclude that A17-mediated feedback inhibition improves the signal to noise ratio of RBC-AII transmission near visual threshold, thereby improving visual sensitivity at night. PMID:25972578

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease.

PubMed

Nörenberg, Dominik; Ebersberger, Hans U; Diederichs, Gerd; Hamm, Bernd; Botnar, René M; Makowski, Marcus R

2016-03-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

Neuron analysis of visual perception

NASA Technical Reports Server (NTRS)

Chow, K. L.

1980-01-01

The receptive fields of single cells in the visual system of cat and squirrel monkey were studied investigating the vestibular input affecting the cells, and the cell's responses during visual discrimination learning process. The receptive field characteristics of the rabbit visual system, its normal development, its abnormal development following visual deprivation, and on the structural and functional re-organization of the visual system following neo-natal and prenatal surgery were also studied. The results of each individual part of each investigation are detailed.

Development of novel two-photon microscopy for living brain and neuron.

PubMed

Nemoto, Tomomi

2014-11-01

"In vivo" two-photon microscopy (TPLSM) has revealed vital information on neural activity for brain function, even in light of its limitation in imaging events at depths greater than a several hundred micrometers from the brain surface. To break the limit of this penetration depth, we introduced a novel light source based on a semiconductor laser [1]. The light source successfully visualized not only cortex layer V pyramidal neurons spreading to all cortex layers at a superior S/N ratio, but visualize hippocampal CA1 neurons in young adult mice [2]. These results indicate that the penetration depth of this laser was ∼1.4 mm. In vivo TPLSM with a laser emitting a longer wavelength might give us insights on activities of neurons in the cortex or the hippocampus. This deep imaging method could be applicable to other living organs including tumor tissues. In addition, we developed liquid crystal devices to convert linearly polarized beams (LP) to vector beams [3]. A liquid device generated a vector beam called higher-order radially polarized (HRP) beam, which enabled that each of the aggregated 0.17 m beads was distinguished individually, whereas in conventional confocal microscopy or TPLSM they could not. We also visualized the finer structures of networks of filamentous cytoskeleton microtubule fluorescently-labeled in the COS-7, and primary culture of mouse neurons. Moreover, by taking an advantage of the LCDs that can utilize various wavelengths including near-infrared, we could employ an HRP beam for improving TPLSM. An HRP beam visualized fine intracellular structures not only in fixed cells stained with various dyes, but also in living cells expressing a fluorescent protein [4]. HRP beam also visualized finer structures of microtubules in fixed cells. Here, we will discuss these improvements and future application on the basis of our recent data.jmicro;63/suppl_1/i7/DFU087F1F1DFU087F1Fig. 1."in vivo" imaging of living mouse brain (H-line). © The Author 2014. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cryo-imaging of fluorescently labeled single cells in a mouse

NASA Astrophysics Data System (ADS)

Steyer, Grant J.; Roy, Debashish; Salvado, Olivier; Stone, Meredith E.; Wilson, David L.

2009-02-01

We developed a cryo-imaging system to provide single-cell detection of fluorescently labeled cells in mouse, with particular applicability to stem cells and metastatic cancer. The Case cryoimaging system consists of a fluorescence microscope, robotic imaging positioner, customized cryostat, PC-based control system, and visualization/analysis software. The system alternates between sectioning (10-40 μm) and imaging, collecting color brightfield and fluorescent blockface image volumes >60GB. In mouse experiments, we imaged quantum-dot labeled stem cells, GFP-labeled cancer and stem cells, and cell-size fluorescent microspheres. To remove subsurface fluorescence, we used a simplified model of light-tissue interaction whereby the next image was scaled, blurred, and subtracted from the current image. We estimated scaling and blurring parameters by minimizing entropy of subtracted images. Tissue specific attenuation parameters were found [uT : heart (267 +/- 47.6 μm), liver (218 +/- 27.1 μm), brain (161 +/- 27.4 μm)] to be within the range of estimates in the literature. "Next image" processing removed subsurface fluorescence equally well across multiple tissues (brain, kidney, liver, adipose tissue, etc.), and analysis of 200 microsphere images in the brain gave 97+/-2% reduction of subsurface fluorescence. Fluorescent signals were determined to arise from single cells based upon geometric and integrated intensity measurements. Next image processing greatly improved axial resolution, enabled high quality 3D volume renderings, and improved enumeration of single cells with connected component analysis by up to 24%. Analysis of image volumes identified metastatic cancer sites, found homing of stem cells to injury sites, and showed microsphere distribution correlated with blood flow patterns. We developed and evaluated cryo-imaging to provide single-cell detection of fluorescently labeled cells in mouse. Our cryo-imaging system provides extreme (>60GB), micron-scale, fluorescence, and bright field image data. Here we describe our image preprocessing, analysis, and visualization techniques. Processing improves axial resolution, reduces subsurface fluorescence by 97%, and enables single cell detection and counting. High quality 3D volume renderings enable us to evaluate cell distribution patterns. Applications include the myriad of biomedical experiments using fluorescent reporter gene and exogenous fluorophore labeling of cells in applications such as stem cell regenerative medicine, cancer, tissue engineering, etc.

Visualizing chemical functionality in plant cell walls

DOE PAGES

Zeng, Yining; Himmel, Michael E.; Ding, Shi-You

2017-11-30

Understanding plant cell wall cross-linking chemistry and polymeric architecture is key to the efficient utilization of biomass in all prospects from rational genetic modification to downstream chemical and biological conversion to produce fuels and value chemicals. In fact, the bulk properties of cell wall recalcitrance are collectively determined by its chemical features over a wide range of length scales from tissue, cellular to polymeric architectures. Microscopic visualization of cell walls from the nanometer to the micrometer scale offers an in situ approach to study their chemical functionality considering its spatial and chemical complexity, particularly the capabilities of characterizing biomass non-destructivelymore » and in real-time during conversion processes. Microscopic characterization has revealed heterogeneity in the distribution of chemical features, which would otherwise be hidden in bulk analysis. Key microscopic features include cell wall type, wall layering, and wall composition - especially cellulose and lignin distributions. Microscopic tools, such as atomic force microscopy, stimulated Raman scattering microscopy, and fluorescence microscopy, have been applied to investigations of cell wall structure and chemistry from the native wall to wall treated by thermal chemical pretreatment and enzymatic hydrolysis. While advancing our current understanding of plant cell wall recalcitrance and deconstruction, microscopic tools with improved spatial resolution will steadily enhance our fundamental understanding of cell wall function.« less

Visualizing chemical functionality in plant cell walls

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

Zeng, Yining; Himmel, Michael E.; Ding, Shi-You

Understanding plant cell wall cross-linking chemistry and polymeric architecture is key to the efficient utilization of biomass in all prospects from rational genetic modification to downstream chemical and biological conversion to produce fuels and value chemicals. In fact, the bulk properties of cell wall recalcitrance are collectively determined by its chemical features over a wide range of length scales from tissue, cellular to polymeric architectures. Microscopic visualization of cell walls from the nanometer to the micrometer scale offers an in situ approach to study their chemical functionality considering its spatial and chemical complexity, particularly the capabilities of characterizing biomass non-destructivelymore » and in real-time during conversion processes. Microscopic characterization has revealed heterogeneity in the distribution of chemical features, which would otherwise be hidden in bulk analysis. Key microscopic features include cell wall type, wall layering, and wall composition - especially cellulose and lignin distributions. Microscopic tools, such as atomic force microscopy, stimulated Raman scattering microscopy, and fluorescence microscopy, have been applied to investigations of cell wall structure and chemistry from the native wall to wall treated by thermal chemical pretreatment and enzymatic hydrolysis. While advancing our current understanding of plant cell wall recalcitrance and deconstruction, microscopic tools with improved spatial resolution will steadily enhance our fundamental understanding of cell wall function.« less

Visualizing chemical functionality in plant cell walls.

PubMed

Zeng, Yining; Himmel, Michael E; Ding, Shi-You

2017-01-01

Understanding plant cell wall cross-linking chemistry and polymeric architecture is key to the efficient utilization of biomass in all prospects from rational genetic modification to downstream chemical and biological conversion to produce fuels and value chemicals. In fact, the bulk properties of cell wall recalcitrance are collectively determined by its chemical features over a wide range of length scales from tissue, cellular to polymeric architectures. Microscopic visualization of cell walls from the nanometer to the micrometer scale offers an in situ approach to study their chemical functionality considering its spatial and chemical complexity, particularly the capabilities of characterizing biomass non-destructively and in real-time during conversion processes. Microscopic characterization has revealed heterogeneity in the distribution of chemical features, which would otherwise be hidden in bulk analysis. Key microscopic features include cell wall type, wall layering, and wall composition-especially cellulose and lignin distributions. Microscopic tools, such as atomic force microscopy, stimulated Raman scattering microscopy, and fluorescence microscopy, have been applied to investigations of cell wall structure and chemistry from the native wall to wall treated by thermal chemical pretreatment and enzymatic hydrolysis. While advancing our current understanding of plant cell wall recalcitrance and deconstruction, microscopic tools with improved spatial resolution will steadily enhance our fundamental understanding of cell wall function.

Locomotion Enhances Neural Encoding of Visual Stimuli in Mouse V1

PubMed Central

2017-01-01

Neurons in mouse primary visual cortex (V1) are selective for particular properties of visual stimuli. Locomotion causes a change in cortical state that leaves their selectivity unchanged but strengthens their responses. Both locomotion and the change in cortical state are thought to be initiated by projections from the mesencephalic locomotor region, the latter through a disinhibitory circuit in V1. By recording simultaneously from a large number of single neurons in alert mice viewing moving gratings, we investigated the relationship between locomotion and the information contained within the neural population. We found that locomotion improved encoding of visual stimuli in V1 by two mechanisms. First, locomotion-induced increases in firing rates enhanced the mutual information between visual stimuli and single neuron responses over a fixed window of time. Second, stimulus discriminability was improved, even for fixed population firing rates, because of a decrease in noise correlations across the population. These two mechanisms contributed differently to improvements in discriminability across cortical layers, with changes in firing rates most important in the upper layers and changes in noise correlations most important in layer V. Together, these changes resulted in a threefold to fivefold reduction in the time needed to precisely encode grating direction and orientation. These results support the hypothesis that cortical state shifts during locomotion to accommodate an increased load on the visual system when mice are moving. SIGNIFICANCE STATEMENT This paper contains three novel findings about the representation of information in neurons within the primary visual cortex of the mouse. First, we show that locomotion reduces by at least a factor of 3 the time needed for information to accumulate in the visual cortex that allows the distinction of different visual stimuli. Second, we show that the effect of locomotion is to increase information in cells of all layers of the visual cortex. Third, we show that the means by which information is enhanced by locomotion differs between the upper layers, where the major effect is the increasing of firing rates, and in layer V, where the major effect is the reduction in noise correlations. PMID:28264980

Cellular Therapy With Human Autologous Adipose-Derived Adult Stem Cells for Advanced Keratoconus.

PubMed

Alió Del Barrio, Jorge L; El Zarif, Mona; de Miguel, María P; Azaar, Albert; Makdissy, Norman; Harb, Walid; El Achkar, Ibrahim; Arnalich-Montiel, Francisco; Alió, Jorge L

2017-08-01

The aim of this phase 1 study was to preliminarily evaluate the safety and efficacy of autologous adipose-derived adult stem cell (ADASC) implantation within the corneal stroma of patients with advanced keratoconus. Five consecutive patients were selected. Autologous ADASCs were obtained by elective liposuction. ADASCs (3 × 10) contained in 1 mL saline were injected into the corneal stroma through a femtosecond-assisted 9.5-mm diameter lamellar pocket under topical anesthesia. Patients were reviewed at 1 day, 1 week, 1, 3, and 6 months postoperatively. Visual function, manifest refraction, slit-lamp biomicroscopy, intraocular pressure, endothelial cell density, corneal topography, corneal optical coherence tomography, and corneal confocal biomicroscopy were recorded. No intraoperative or postoperative complications were recorded, with full corneal transparency recovery within 24 hours. Four patients completed the full follow-up. All patients improved their visual function (mean: 1 line of unaided and spectacle-corrected distance vision and 2 lines of rigid contact lens distance vision). Manifest refraction and topographic keratometry remained stable. Corneal optical coherence tomography showed a mean improvement of 16.5 μm in the central corneal thickness, and new collagen production was observed as patchy hyperreflective areas at the level of the stromal pocket. Confocal biomicroscopy confirmed the survival of the implanted stem cells at the surgical plane. Intraocular pressure and endothelial cell density remained stable. Cellular therapy of the human corneal stroma in vivo with autologous ADASCs appears to be safe. Stem cells survive in vivo with intrastromal new collagen production. Future studies with larger samples are required to confirm these preliminary results.

Novel full‐spectral flow cytometry with multiple spectrally‐adjacent fluorescent proteins and fluorochromes and visualization of in vivo cellular movement

PubMed Central

Futamura, Koji; Sekino, Masashi; Hata, Akihiro; Ikebuchi, Ryoyo; Nakanishi, Yasutaka; Egawa, Gyohei; Kabashima, Kenji; Watanabe, Takeshi; Furuki, Motohiro

2015-01-01

Abstract Flow cytometric analysis with multicolor fluoroprobes is an essential method for detecting biological signatures of cells. Here, we present a new full‐spectral flow cytometer (spectral‐FCM). Unlike conventional flow cytometer, this spectral‐FCM acquires the emitted fluorescence for all probes across the full‐spectrum from each cell with 32 channels sequential PMT unit after dispersion with prism, and extracts the signals of each fluoroprobe based on the spectral shape of each fluoroprobe using unique algorithm in high speed, high sensitive, accurate, automatic and real‐time. The spectral‐FCM detects the continuous changes in emission spectra from green to red of the photoconvertible protein, KikGR with high‐spectral resolution and separates spectrally‐adjacent fluoroprobes, such as FITC (Emission peak (Em) 519 nm) and EGFP (Em 507 nm). Moreover, the spectral‐FCM can measure and subtract autofluorescence of each cell providing increased signal‐to‐noise ratios and improved resolution of dim samples, which leads to a transformative technology for investigation of single cell state and function. These advances make it possible to perform 11‐color fluorescence analysis to visualize movement of multilinage immune cells by using KikGR‐expressing mice. Thus, the novel spectral flow cytometry improves the combinational use of spectrally‐adjacent various FPs and multicolor fluorochromes in metabolically active cell for the investigation of not only the immune system but also other research and clinical fields of use. © 2015 The Authors. Cytometry Part A Published by Wiley Periodicals, Inc. on behalf of ISAC PMID:26217952

Correlation of visual in vitro cytotoxicity ratings of biomaterials with quantitative in vitro cell viability measurements.

PubMed

Bhatia, Sujata K; Yetter, Ann B

2008-08-01

Medical devices and implanted biomaterials are often assessed for biological reactivity using visual scores of cell-material interactions. In such testing, biomaterials are assigned cytotoxicity ratings based on visual evidence of morphological cellular changes, including cell lysis, rounding, spreading, and proliferation. For example, ISO 10993 cytotoxicity testing of medical devices allows the use of a visual grading scale. The present study compared visual in vitro cytotoxicity ratings to quantitative in vitro cytotoxicity measurements for biomaterials to determine the level of correlation between visual scoring and a quantitative cell viability assay. Biomaterials representing a spectrum of biological reactivity levels were evaluated, including organo-tin polyvinylchloride (PVC; a known cytotoxic material), ultra-high molecular weight polyethylene (a known non-cytotoxic material), and implantable tissue adhesives. Each material was incubated in direct contact with mouse 3T3 fibroblast cell cultures for 24 h. Visual scores were assigned to the materials using a 5-point rating scale; the scorer was blinded to the material identities. Quantitative measurements of cell viability were performed using a 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay; again, the assay operator was blinded to material identities. The investigation revealed a high degree of correlation between visual cytotoxicity ratings and quantitative cell viability measurements; a Pearson's correlation gave a correlation coefficient of 0.90 between the visual cytotoxicity score and the percent viable cells. An equation relating the visual cytotoxicity score and the percent viable cells was derived. The results of this study are significant for the design and interpretation of in vitro cytotoxicity studies of novel biomaterials.

Improvement of 19F MR image uniformity in a mouse model of cellular therapy using inductive coupling.

PubMed

Park, Bu S; Ma, Ge; Koch, William T; Rajan, Sunder S; Mastromanolis, Manuel; Lam, Johnny; Sung, Kyung; McCright, Brent

2018-06-15

Improve 19 F magnetic resonance imaging uniformity of perfluorocarbon (PFC)-labeled cells by using a secondary inductive resonator tuned to 287 MHz to enhance the induced radio frequency (RF) magnetic field (B 1 ) at 7.05 T. Following Faraday's induction law, the sign of induced B 1 made by the secondary resonator can be changed depending on the tuning of the resonator. A secondary resonator located on the opposite side of the phantom of the 19 F surface coil can be shown to enhance or subtract the induced B 1 field, depending upon its tuning. The numerical simulation results of rotating transmit B 1 magnitude (|B 1 + |) and corresponding experimental 19 F images were compared without and with the secondary resonator. With the secondary resonator tuned to 287 MHz, improvements of |B 1 + | and 19 F image uniformity were demonstrated. The use of the secondary resonator improved our ability to visualize transplanted cell location non-invasively over a period of 6 weeks. The secondary resonator tuned to enhance the induced B 1 results in improved image uniformity in a pre-clinical application, enabling cell tracking of PFC-labeled cells with the secondary resonator.

Live-cell CRISPR imaging in plants reveals dynamic telomere movements.

PubMed

Dreissig, Steven; Schiml, Simon; Schindele, Patrick; Weiss, Oda; Rutten, Twan; Schubert, Veit; Gladilin, Evgeny; Mette, Michael F; Puchta, Holger; Houben, Andreas

2017-08-01

Elucidating the spatiotemporal organization of the genome inside the nucleus is imperative to our understanding of the regulation of genes and non-coding sequences during development and environmental changes. Emerging techniques of chromatin imaging promise to bridge the long-standing gap between sequencing studies, which reveal genomic information, and imaging studies that provide spatial and temporal information of defined genomic regions. Here, we demonstrate such an imaging technique based on two orthologues of the bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 (Cas9). By fusing eGFP/mRuby2 to catalytically inactive versions of Streptococcus pyogenes and Staphylococcus aureus Cas9, we show robust visualization of telomere repeats in live leaf cells of Nicotiana benthamiana. By tracking the dynamics of telomeres visualized by CRISPR-dCas9, we reveal dynamic telomere movements of up to 2 μm over 30 min during interphase. Furthermore, we show that CRISPR-dCas9 can be combined with fluorescence-labelled proteins to visualize DNA-protein interactions in vivo. By simultaneously using two dCas9 orthologues, we pave the way for the imaging of multiple genomic loci in live plants cells. CRISPR imaging bears the potential to significantly improve our understanding of the dynamics of chromosomes in live plant cells. © 2017 The Authors The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer.

PubMed

Bennicelli, Jeannette; Wright, John Fraser; Komaromy, Andras; Jacobs, Jonathan B; Hauck, Bernd; Zelenaia, Olga; Mingozzi, Federico; Hui, Daniel; Chung, Daniel; Rex, Tonia S; Wei, Zhangyong; Qu, Guang; Zhou, Shangzhen; Zeiss, Caroline; Arruda, Valder R; Acland, Gregory M; Dell'Osso, Lou F; High, Katherine A; Maguire, Albert M; Bennett, Jean

2008-03-01

We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models of the RPE65 form of Leber congenital amaurosis (LCA). Protein expression was optimized by addition of a modified Kozak sequence at the translational start site of hRPE65. Modifications in AAV production and delivery included use of a long stuffer sequence to prevent reverse packaging from the AAV inverted-terminal repeats, and co-injection with a surfactant. The latter allows consistent and predictable delivery of a given dose of vector. We observed improved electroretinograms (ERGs) and visual acuity in Rpe65 mutant mice. This has not been reported previously using AAV2 vectors. Subretinal delivery of 8.25 x 10(10) vector genomes in affected dogs was well tolerated both locally and systemically, and treated animals showed improved visual behavior and pupillary responses, and reduced nystagmus within 2 weeks of injection. ERG responses confirmed the reversal of visual deficit. Immunohistochemistry confirmed transduction of retinal pigment epithelium cells and there was minimal toxicity to the retina as judged by histopathologic analysis. The data demonstrate that AAV2.RPE65 delivers the RPE65 transgene efficiently and quickly to the appropriate target cells in vivo in animal models. This vector holds great promise for treatment of LCA due to RPE65 mutations.

Reversal of Blindness in Animal Models of Leber Congenital Amaurosis Using Optimized AAV2-mediated Gene Transfer

PubMed Central

Bennicelli, Jeannette; Wright, John Fraser; Komaromy, Andras; Jacobs, Jonathan B; Hauck, Bernd; Zelenaia, Olga; Mingozzi, Federico; Hui, Daniel; Chung, Daniel; Rex, Tonia S; Wei, Zhangyong; Qu, Guang; Zhou, Shangzhen; Zeiss, Caroline; Arruda, Valder R; Acland, Gregory M; Dell’Osso, Lou F; High, Katherine A; Maguire, Albert M; Bennett, Jean

2010-01-01

We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models of the RPE65 form of Leber congenital amaurosis (LCA). Protein expression was optimized by addition of a modified Kozak sequence at the translational start site of hRPE65. Modifications in AAV production and delivery included use of a long stuffer sequence to prevent reverse packaging from the AAV inverted-terminal repeats, and co-injection with a surfactant. The latter allows consistent and predictable delivery of a given dose of vector. We observed improved electroretinograms (ERGs) and visual acuity in Rpe65 mutant mice. This has not been reported previously using AAV2 vectors. Subretinal delivery of 8.25 × 1010 vector genomes in affected dogs was well tolerated both locally and systemically, and treated animals showed improved visual behavior and pupillary responses, and reduced nystagmus within 2 weeks of injection. ERG responses confirmed the reversal of visual deficit. Immunohistochemistry confirmed transduction of retinal pigment epithelium cells and there was minimal toxicity to the retina as judged by histopathologic analysis. The data demonstrate that AAV2.RPE65 delivers the RPE65 transgene efficiently and quickly to the appropriate target cells in vivo in animal models. This vector holds great promise for treatment of LCA due to RPE65 mutations. PMID:18209734

Nutrition in brain development and aging: role of essential fatty acids.

PubMed

Uauy, Ricardo; Dangour, Alan D

2006-05-01

The essential fatty acids (EFAs), particularly the n-3 long-chain polyunsaturated fatty acids (LCPs), are important for brain development during both the fetal and postnatal period. They are also increasingly seen to be of value in limiting the cognitive decline during aging. EFA deficiency was first shown over 75 years ago, but the more subtle effects of the n-3 fatty acids in terms of skin changes, a poor response to linoleic acid supplementation, abnormal visual function, and peripheral neuropathy were only discovered later. Both n-3 and n-6 LCPs play important roles in neuronal growth, development of synaptic processing of neural cell interaction, and expression of genes regulating cell differentiation and growth. The fetus and placenta are dependent on maternal EFA supply for their growth and development, with docosahexaenomic acid (DHA)-supplemented infants showing significantly greater mental and psychomotor development scores (breast-fed children do even better). Dietary DHA is needed for the optimum functional maturation of the retina and visual cortex, with visual acuity and mental development seemingly improved by extra DHA. Aging is also associated with decreased brain levels of DHA: fish consumption is associated with decreased risk of dementia and Alzheimer's disease, and the reported daily use of fish-oil supplements has been linked to improved cognitive function scores, but confirmation of these effects is needed.

New light for old eyes: comparing melanopsin-mediated non-visual benefits of blue-light and UV-blocking intraocular lenses.

PubMed

Schmoll, Conrad; Khan, Ashraf; Aspinall, Peter; Goudie, Colin; Koay, Peter; Tendo, Christelle; Cameron, James; Roe, Jenny; Deary, Ian; Dhillon, Bal

2014-01-01

Melanopsin-expressing photosensitive retinal ganglion cells form a blue-light-sensitive non-visual system mediating diverse physiological effects including circadian entrainment and cognitive alertness. Reduced blue wavelength retinal illumination through cataract formation is thought to blunt these responses while cataract surgery and intraocular lens (IOL) implantation have been shown to have beneficial effects on sleep and cognition. We aimed to use the reaction time (RT) task and the Epworth Sleepiness Score (ESS) as a validated objective platform to compare non-visual benefits of UV- and blue-blocking IOLs. Patients were prospectively randomised to receive either a UV- or blue-blocking IOL, performing an RT test and ESS questionnaire before and after surgery. Optical blurring at the second test controlled for visual improvement. Non-operative age-matched controls were recruited for comparison. 80 participants completed the study. Those undergoing first-eye phacoemulsification demonstrated significant improvements in RT over control (p=0.001) and second-eye surgery patients (p=0.03). Moreover, reduced daytime sleepiness was measured by ESS for the first-eye surgery group (p=0.008) but not for the second-eye group (p=0.09). Choice of UV- or blue-blocking IOL made no significant difference to magnitude of cognitive improvement (p=0.272). Phacoemulsification, particularly first-eye surgery, has a strong positive effect on cognition and daytime alertness, regardless of IOL type.

Neural networks improve brain cancer detection with Raman spectroscopy in the presence of operating room light artifacts

NASA Astrophysics Data System (ADS)

Jermyn, Michael; Desroches, Joannie; Mercier, Jeanne; Tremblay, Marie-Andrée; St-Arnaud, Karl; Guiot, Marie-Christine; Petrecca, Kevin; Leblond, Frederic

2016-09-01

Invasive brain cancer cells cannot be visualized during surgery and so they are often not removed. These residual cancer cells give rise to recurrences. In vivo Raman spectroscopy can detect these invasive cancer cells in patients with grade 2 to 4 gliomas. The robustness of this Raman signal can be dampened by spectral artifacts generated by lights in the operating room. We found that artificial neural networks (ANNs) can overcome these spectral artifacts using nonparametric and adaptive models to detect complex nonlinear spectral characteristics. Coupling ANN with Raman spectroscopy simplifies the intraoperative use of Raman spectroscopy by limiting changes required to the standard neurosurgical workflow. The ability to detect invasive brain cancer under these conditions may reduce residual cancer remaining after surgery and improve patient survival.

A novel method for accurate patterning and positioning of biological cells

NASA Astrophysics Data System (ADS)

Jing, Gaoshan; Labukas, Joseph P.; Iqbal, Aziz; Perry, Susan Fueshko; Ferguson, Gregory S.; Tatic-Lucic, Svetlana

2007-05-01

The ability to anchor cells in predefined patterns on a surface has become very important for the development of cell-based sensors, tissue-engineering applications, and the understanding of basic cell functions. Currently, the most widely used technique to generate micrometer or sub-micrometer-sized patterns for various biological applications is microcontact printing (μCP). However, the fidelity of the final pattern may be compromised by deformation of the PDMS stamps used during printing. A novel technique for accurately patterning and positioning biological cells is presented, which can overcome this obstacle. We have fabricated a chip on a silicon wafer using standard photolithographic and deposition processes consisting of gold patterns on top of PECVD silicon dioxide. A hydrophobic self-assembled monolayer (SAM) derived from 1-hexadecanethiol (HDT) was coated on the gold surface to prevent cell growth, and a hydrophilic SAM derived from (3-trimethoxysilyl propyl)-diethylenetriamine (DETA) was coated on the exposed PECVD silicon dioxide surface to promote cell growth. Immortalized mouse hypothalamic neurons (GT1-7) were cultured in vitro on the chip, and patterned cells were fluorescently stained and visualized by fluorescence microscopy. By our method, hydrophobic and hydrophilic regions can be reliably generated and easily visualized under a microscope prior to cell culturing. Cell growth was precisely controlled and limited to specific areas. The achieved resolution was 2 microns, and it could be improved with high resolution photolithographic methods.

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.

PubMed

Mehat, Manjit S; Sundaram, Venki; Ripamonti, Caterina; Robson, Anthony G; Smith, Alexander J; Borooah, Shyamanga; Robinson, Martha; Rosenthal, Adam N; Innes, William; Weleber, Richard G; Lee, Richard W J; Crossland, Michael; Rubin, Gary S; Dhillon, Baljean; Steel, David H W; Anglade, Eddy; Lanza, Robert P; Ali, Robin R; Michaelides, Michel; Bainbridge, James W B

2018-06-05

Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area. Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.gov identifier, NCT01469832). Twelve participants with advanced Stargardt disease (STGD1), the most common cause of macular degeneration in children and young adults. Subretinal transplantation of up to 200 000 hESC-derived RPE cells with systemic immunosuppressive therapy for 13 weeks. The primary end points were the safety and tolerability of hESC-derived RPE cell administration. We also investigated evidence of the survival of transplanted cells and measured retinal structure and function using microperimetry and spectral-domain OCT. Focal areas of subretinal hyperpigmentation developed in all participants in a dose-dependent manner in the recipient retina and persisted after withdrawal of systemic immunosuppression. We found no evidence of uncontrolled proliferation or inflammatory responses. Borderline improvements in best-corrected VA in 4 participants either were unsustained or were matched by a similar improvement in the untreated contralateral eye. Microperimetry demonstrated no evidence of benefit at 12 months in the 12 participants. In one instance at the highest dose, localized retinal thinning and reduced sensitivity in the area of hyperpigmentation suggested the potential for harm. Participant-reported quality of life using the 25-item National Eye Institute Visual Function Questionnaire indicated no significant change. Subretinal hyperpigmentation is consistent with the survival of viable transplanted hESC-derived RPE cells, but may reflect released pigment in their absence. The findings demonstrate the value of detailed analysis of spatial correlation of retinal structure and function in determining with appropriate sensitivity the impact of cell transplantation and suggest that intervention in early stage of disease should be approached with caution. Given the slow rate of progressive degeneration at this advanced stage of disease, any protection against further deterioration may be evident only after a more extended period of observation. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results.

PubMed

Nordström, Maria; Schiller, Maria; Fredriksson, Anneli; Behndig, Anders

2017-07-01

To assess the refractive improvements and the corneal endothelial safety of an individualised topography-guided regimen for corneal crosslinking in progressive keratoconus. An open-label prospective randomised clinical trial was performed at the Department of Clinical Sciences, Ophthalmology, Umeå University Hospital, Umeå, Sweden. Thirty-seven patients (50 eyes) with progressive keratoconus planned for corneal crosslinking were included. The patients were randomised to topography-guided crosslinking (photorefractive intrastromal crosslinking (PiXL); n=25) or uniform 9 mm crosslinking (corneal collagen crosslinking (CXL); n=25). Visual acuity, refraction, keratometry (K1, K2 and K max ) and corneal endothelial morphometry were assessed preoperatively and at 1, 3, 6 and 12 months postoperatively. The PiXL treatment involved an asymmetrical treatment zone centred on the area of maximum corneal steepness with treatment energies ranging from 7.2 to 15.0 J/cm 2 ; the CXL treatment was a uniform 9 mm 5.4 J/cm 2 pulsed crosslinking. The main outcome measures were changes in refractive errors and corneal endothelial cell density. The spherical refractive errors decreased (p<0.05) and the visual acuity improved (p<0.01) at 3, 6 and 12 months after PiXL, but not after CXL. The between-groups differences, however, were not significant. K2 and K max decreased at 3, 6 and 12 months after PiXL (p<0.01), but not after CXL (p<0.01 when comparing the two treatments). No corneal endothelial cell loss was seen after either treatment. Individualised topography-based crosslinking treatment centred on the ectatic cone has the potential to improve the corneal shape in keratoconus with decreased spherical refractive errors and improved visual acuity, without damage to the corneal endothelium. NCT02514200, Results. 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/.

Segregation of Visual Response Properties in the Mouse Superior Colliculus and Their Modulation during Locomotion

PubMed Central

2017-01-01

The superior colliculus (SC) receives direct input from the retina and integrates it with information about sound, touch, and state of the animal that is relayed from other parts of the brain to initiate specific behavioral outcomes. The superficial SC layers (sSC) contain cells that respond to visual stimuli, whereas the deep SC layers (dSC) contain cells that also respond to auditory and somatosensory stimuli. Here, we used a large-scale silicon probe recording system to examine the visual response properties of SC cells of head-fixed and alert male mice. We found cells with diverse response properties including: (1) orientation/direction-selective (OS/DS) cells with a firing rate that is suppressed by drifting sinusoidal gratings (negative OS/DS cells); (2) suppressed-by-contrast cells; (3) cells with complex-like spatial summation nonlinearity; and (4) cells with Y-like spatial summation nonlinearity. We also found specific response properties that are enriched in different depths of the SC. The sSC is enriched with cells with small RFs, high evoked firing rates (FRs), and sustained temporal responses, whereas the dSC is enriched with the negative OS/DS cells and with cells with large RFs, low evoked FRs, and transient temporal responses. Locomotion modulates the activity of the SC cells both additively and multiplicatively and changes the preferred spatial frequency of some SC cells. These results provide the first description of the negative OS/DS cells and demonstrate that the SC segregates cells with different response properties and that the behavioral state of a mouse affects SC activity. SIGNIFICANCE STATEMENT The superior colliculus (SC) receives visual input from the retina in its superficial layers (sSC) and induces eye/head-orientating movements and innate defensive responses in its deeper layers (dSC). Despite their importance, very little is known about the visual response properties of dSC neurons. Using high-density electrode recordings and novel model-based analysis, we found several novel visual response properties of the SC cells, including encoding of a cell's preferred orientation or direction by suppression of the firing rate. The sSC and the dSC are enriched with cells with different visual response properties. Locomotion modulates the cells in the SC. These findings contribute to our understanding of how the SC processes visual inputs, a critical step in comprehending visually guided behaviors. PMID:28760858

Visualization of AMR data with multi-level dual-mesh interpolation.

PubMed

Moran, Patrick J; Ellsworth, David

2011-12-01

We present a new technique for providing interpolation within cell-centered Adaptive Mesh Refinement (AMR) data that achieves C(0) continuity throughout the 3D domain. Our technique improves on earlier work in that it does not require that adjacent patches differ by at most one refinement level. Our approach takes the dual of each mesh patch and generates "stitching cells" on the fly to fill the gaps between dual meshes. We demonstrate applications of our technique with data from Enzo, an AMR cosmological structure formation simulation code. We show ray-cast visualizations that include contributions from particle data (dark matter and stars, also output by Enzo) and gridded hydrodynamic data. We also show results from isosurface studies, including surfaces in regions where adjacent patches differ by more than one refinement level. © 2011 IEEE

Molecular medicine in ophthalmic care.

PubMed

Richer, Stuart; Stiles, William; Thomas, Carla

2009-12-01

Lipofuscin is the most consistent and phylogenically constant morphologic marker of cellular aging. Autofluorescence of the A2E fluorophore within retinal pigment epithelial (RPE) lipofuscin affords the opportunity for noninvasive evaluation of age- and disease-related pathophysiological changes in the human retina. It is being used in National Eye Institute/Age-Related Eye Disease Study II to evaluate age-related macular degeneration (AMD) geographic atrophy expansion. Experiments show lipofuscin can be reversed in cell culture and animal models in heart, brain, spinal cord, and retinal tissues, using an array of antioxidants and iron chelators. An 80-year-old man with a gastric resection presented with complaints of unremitting night driving difficulty despite treatment with lutein and omega III fatty acids. Notable parafoveal deposition of retinal lipofuscin by 50 degrees fundus auto-fluorescence (580 nm excitation/660 barrier filters) and concurrent abnormalities in non-Snellen measures of visual function-Contrast Sensitivity Function, 6.5 degrees large field tritan threshold, 10 degrees threshold visual fields, and deficits in the National Institutes of Health/National Eye Institute Visual Function Questionnaire (VFQ) 25 subjective night driving/mental health subscale questionnaire were obtained. The patient was placed on an over-the-counter daily oral polyphenolic mixture containing resveratrol and re-evaluated 5 months later. The data reveal improvements in all measures of visual function, subjective improvement in vision and mental functioning on the VFQ 25, and visible clearing of RPE lipofuscin. To our knowledge, we believe this to be the first reported human clinical case of lipofuscin reversal in the human eye correlated with measured clinical and subjective improvement in visual and mental function after nutraceutical intervention.

CellMap visualizes protein-protein interactions and subcellular localization

PubMed Central

Dallago, Christian; Goldberg, Tatyana; Andrade-Navarro, Miguel Angel; Alanis-Lobato, Gregorio; Rost, Burkhard

2018-01-01

Many tools visualize protein-protein interaction (PPI) networks. The tool introduced here, CellMap, adds one crucial novelty by visualizing PPI networks in the context of subcellular localization, i.e. the location in the cell or cellular component in which a PPI happens. Users can upload images of cells and define areas of interest against which PPIs for selected proteins are displayed (by default on a cartoon of a cell). Annotations of localization are provided by the user or through our in-house database. The visualizer and server are written in JavaScript, making CellMap easy to customize and to extend by researchers and developers. PMID:29497493

Sudden visual loss after cardiac resynchronization therapy device implantation.

PubMed

De Vitis, Luigi A; Marchese, Alessandro; Giuffrè, Chiara; Carnevali, Adriano; Querques, Lea; Tomasso, Livia; Baldin, Giovanni; Maestranzi, Gisella; Lattanzio, Rosangela; Querques, Giuseppe; Bandello, Francesco

2017-03-10

To report a case of sudden decrease in visual acuity possibly due to a cardiogenic embolism in a patient who underwent cardiac resynchronization therapy (CRT) device implantation. A 62-year-old man with severe left ventricular systolic dysfunction and a left bundle branch block was referred to our department because of a sudden decrease in visual acuity. Nine days earlier, he had undergone cardiac transapical implantation of a CRT device, which was followed, 2 days later, by an inflammatory reaction. The patient underwent several general and ophthalmologic examinations, including multimodal imaging. At presentation, right eye (RE) best-corrected visual acuity (BCVA) was counting fingers and RE pupil was hyporeactive. Fundus examination revealed white-centered hemorrhagic dots suggestive of Roth spots. Fluorescein angiography showed delay in vascular perfusion during early stage, late hyperfluorescence of the macula and optic disk, and peripheral perivascular leakage. The first visual field test showed complete loss of vision RE and a normal left eye. Due to suspected giant cell arteritis, temporal artery biopsy was performed. Thirty minutes after the procedure, an ischemic stroke with right hemisyndrome and aphasia occurred. The RE BCVA worsened to hands motion. Four months later, RE BCVA did not improve, despite improvement in fluorescein angiography inflammatory sign. We report a possible cardiogenic embolism secondary to undiagnosed infective endocarditis causing monocular visual loss after CRT device implantation. It remains unclear how the embolus caused severe functional damage without altering the retinal anatomical structure.

Update on Clinical Trials in Dry Age-related Macular Degeneration

PubMed Central

Taskintuna, Ibrahim; Elsayed, M. E. A. Abdalla; Schatz, Patrik

2016-01-01

This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future. PMID:26957835

Techniques to improve the direct ex vivo detection of low frequency antigen-specific CD8+ T cells with peptide-major histocompatibility complex class I tetramers

PubMed Central

Chattopadhyay, Pratip K.; Melenhorst, J. Joseph; Ladell, Kristin; Gostick, Emma; Scheinberg, Philip; Barrett, A. John; Wooldridge, Linda; Roederer, Mario; Sewell, Andrew K.; Price, David A.

2008-01-01

The ability to quantify and characterize antigen-specific CD8+ T cells irrespective of functional readouts using fluorochrome-conjugated tetrameric peptide-MHC class I (pMHCI) complexes in conjunction with flow cytometry has transformed our understanding of cellular immune responses over the past decade. In the case of prevalent CD8+ T cell populations that engage cognate pMHCI tetramers with high avidities, direct ex vivo identification and subsequent data interpretation is relatively straightforward. However, the accurate identification of low frequency antigen-specific CD8+ T cell populations can be complicated, especially in situations where TCR-mediated tetramer binding occurs at low avidities. Here, we highlight a few simple techniques that can be employed to improve the visual resolution, and hence the accurate quantification, of tetramer-binding CD8+ T cell populations by flow cytometry. These methodological modifications enhance signal intensity, especially in the case of specific CD8+ T cell populations that bind cognate antigen with low avidity, minimize background noise and enable improved discrimination of true pMHCI tetramer binding events from nonspecific uptake. PMID:18836993

A medaka model of cancer allowing direct observation of transplanted tumor cells in vivo at a cellular-level resolution.

PubMed

Hasegawa, Sumitaka; Maruyama, Kouichi; Takenaka, Hikaru; Furukawa, Takako; Saga, Tsuneo

2009-08-18

The recent success with small fish as an animal model of cancer with the aid of fluorescence technique has attracted cancer modelers' attention because it would be possible to directly visualize tumor cells in vivo in real time. Here, we report a medaka model capable of allowing the observation of various cell behaviors of transplanted tumor cells, such as cell proliferation and metastasis, which were visualized easily in vivo. We established medaka melanoma (MM) cells stably expressing GFP and transplanted them into nonirradiated and irradiated medaka. The tumor cells were grown at the injection sites in medaka, and the spatiotemporal changes were visualized under a fluorescence stereoscopic microscope at a cellular-level resolution, and even at a single-cell level. Tumor dormancy and metastasis were also observed. Interestingly, in irradiated medaka, accelerated tumor growth and metastasis of the transplanted tumor cells were directly visualized. Our medaka model provides an opportunity to visualize in vivo tumor cells "as seen in a culture dish" and would be useful for in vivo tumor cell biology.

Phosphene phenomenon: a new concept.

PubMed

Bókkon, István

2008-05-01

This paper proposes a new biopsychophysical concept of phosphene phenomenon. Namely, visual sensation of phosphenes is due to the intrinsic perception of ultraweak bioluminescent photon emission of cells in the visual system. In other words, phosphenes are bioluminescent biophotons in the visual system induced by various stimuli (mechanical, electrical, magnetic, ionizing radiation, etc.) as well as random bioluminescent biophotons firings of cells in the visual pathway. This biophoton emission can become conscious if induced or spontaneous biophoton emission of cells in the visual system exceeds a distinct threshold. Neuronal biophoton communication can occur by means of non-visual neuronal opsins and natural photosensitive biomolecules. Our interpretation is in direct connection with the functional roles of free radicals and excited biomolecules in living cells.

Adaptations for vision in dim light: impulse responses and bumps in nocturnal spider photoreceptor cells (Cupiennius salei Keys).

PubMed

Pirhofer-Walzl, Karin; Warrant, Eric; Barth, Friedrich G

2007-10-01

The photoreceptor cells of the nocturnal spider Cupiennius salei were investigated by intracellular electrophysiology. (1) The responses of photoreceptor cells of posterior median (PM) and anterior median (AM) eyes to short (2 ms) light pulses showed long integration times in the dark-adapted and shorter integration times in the light-adapted state. (2) At very low light intensities, the photoreceptors responded to single photons with discrete potentials, called bumps, of high amplitude (2-20 mV). When measured in profoundly dark-adapted photoreceptor cells of the PM eyes these bumps showed an integration time of 128 +/- 35 ms (n = 7) whereas in dark-adapted photoreceptor cells of AM eyes the integration time was 84 +/- 13 ms (n = 8), indicating that the AM eyes are intrinsically faster than the PM eyes. (3) Long integration times, which improve visual reliability in dim light, and large responses to single photons in the dark-adapted state, contribute to a high visual sensitivity in Cupiennius at night. This conclusion is underlined by a calculation of sensitivity that accounts for both anatomical and physiological characteristics of the eye.

Objective automated quantification of fluorescence signal in histological sections of rat lens.

PubMed

Talebizadeh, Nooshin; Hagström, Nanna Zhou; Yu, Zhaohua; Kronschläger, Martin; Söderberg, Per; Wählby, Carolina

2017-08-01

Visual quantification and classification of fluorescent signals is the gold standard in microscopy. The purpose of this study was to develop an automated method to delineate cells and to quantify expression of fluorescent signal of biomarkers in each nucleus and cytoplasm of lens epithelial cells in a histological section. A region of interest representing the lens epithelium was manually demarcated in each input image. Thereafter, individual cell nuclei within the region of interest were automatically delineated based on watershed segmentation and thresholding with an algorithm developed in Matlab™. Fluorescence signal was quantified within nuclei, cytoplasms and juxtaposed backgrounds. The classification of cells as labelled or not labelled was based on comparison of the fluorescence signal within cells with local background. The classification rule was thereafter optimized as compared with visual classification of a limited dataset. The performance of the automated classification was evaluated by asking 11 independent blinded observers to classify all cells (n = 395) in one lens image. Time consumed by the automatic algorithm and visual classification of cells was recorded. On an average, 77% of the cells were correctly classified as compared with the majority vote of the visual observers. The average agreement among visual observers was 83%. However, variation among visual observers was high, and agreement between two visual observers was as low as 71% in the worst case. Automated classification was on average 10 times faster than visual scoring. The presented method enables objective and fast detection of lens epithelial cells and quantification of expression of fluorescent signal with an accuracy comparable with the variability among visual observers. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

CellShape: A user-friendly image analysis tool for quantitative visualization of bacterial cell factories inside.

PubMed

Goñi-Moreno, Ángel; Kim, Juhyun; de Lorenzo, Víctor

2017-02-01

Visualization of the intracellular constituents of individual bacteria while performing as live biocatalysts is in principle doable through more or less sophisticated fluorescence microscopy. Unfortunately, rigorous quantitation of the wealth of data embodied in the resulting images requires bioinformatic tools that are not widely extended within the community-let alone that they are often subject to licensing that impedes software reuse. In this context we have developed CellShape, a user-friendly platform for image analysis with subpixel precision and double-threshold segmentation system for quantification of fluorescent signals stemming from single-cells. CellShape is entirely coded in Python, a free, open-source programming language with widespread community support. For a developer, CellShape enhances extensibility (ease of software improvements) by acting as an interface to access and use existing Python modules; for an end-user, CellShape presents standalone executable files ready to open without installation. We have adopted this platform to analyse with an unprecedented detail the tridimensional distribution of the constituents of the gene expression flow (DNA, RNA polymerase, mRNA and ribosomal proteins) in individual cells of the industrial platform strain Pseudomonas putida KT2440. While the CellShape first release version (v0.8) is readily operational, users and/or developers are enabled to expand the platform further. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Influence AquaLase at corneal endothelial cells].

PubMed

Jirásková, N; Rozsíval, P; Ludvíková, M; Burova, M; Nekolová, J

2009-07-01

To assess the effect of the cleaning of the posterior capsule using pulses of balanced salt solution (BSS) on the corneal endothelial cells. This pilot study involves 43 patients with bilateral cataracts having lens removal using torsional phacoemulsification (Ozil, Infiniti, Alcon) and bimanul irrigation/aspiration (I/A). Posterior capsule of the right eye of each patient was cleaned using pulses of BSS (AquaLase, Infiniti, Alcon). Surgery was performed by one of 2 surgeons (NJ, PR), both eyes of each patient was operated on by the same surgeon. Best corrected visual acuity (BCVA), endotelial cell count and pachymetry were evaluated pre- and postoperatively as well as occurence af peri- and postoperative complications. Preoperative mean pachymetry (P) was 566 +/- 45 microm in the right eye (RE) and 562 +/- 42 microm in the left eye (LE), mean endotelial cell count (ECC) 2541 +/- 317 cells/mm2 (RE) and 2567 +/- 311 cells/mm2 (LE). Three months after surgery P was 557 +/- 43 microm (RE) and 558 +/- 45 microm (LE) and ECC 2368 +/- 416 cells/mm2 (RE) and 2396 +/- 417 cells/mm2 (LE). There was no statistical difference in postoperative changes of both corneal parameters between right and left eyes. Best corrected visual acuity improved in all eyes and no peri-or postoperative complications occured. Cleaning of the posterior capsule using AquaLase is safe for corneal endothelial cells.

Isolated primary central nervous system lymphoma arising from the optic chiasm.

PubMed

Vassal, F; Pommier, B; Boutet, C; Forest, F; Campolmi, N; Nuti, C

2014-12-01

A 58-year-old previously healthy woman rapidly developed progressive bilateral visual loss. Magnetic resonance imaging revealed a bulging appearance of the optic chiasm, with homogeneous enhancement after gadolinium administration, which suggested an optic glioma or inflammatory disease. In the absence of (para)clinical clues for a specific diagnosis despite extensive investigation, a biopsy of one optic nerve was performed, resulting in a diagnosis of non-Hodgkin B-cell lymphoma. There was no evidence of any other ocular or systemic involvement, therefore the conclusion was that this immunocompetent patient had a primary central nervous system lymphoma isolated in the anterior visual pathway. Treatment included two cycles of polychemotherapy (rituximab, methotrexate, carmustine, etoposide, methylprednisolone), followed by autologous peripheral blood stem cell transplantation and rituximab plus cytarabine consolidation therapy. Subsequently, the patient exhibited significant improvement in vision, and was still disease-free at the 1-year follow-up examination. The aim of the present paper was to provide well-documented clinical, radiological, and intraoperative features of isolated primary malignant lymphoma arising from the anterior visual pathway. A better recognition of this rare pathological entity is necessary for clinicians who may encounter similar presentations, as prompt management is crucial for both a visual and vital prognosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Isolating Attention Systems: A Cognitive-Anatomical Analysis. Cognitive Science Program, Technical Report No. 86-3.

ERIC Educational Resources Information Center

Posner, Michael I.; And Others

Recently, knowledge of the mechanisms of visual-spatial attention has improved due to studies employing single cell recording with alert monkeys and studies using performance analysis of neurological patients. These studies suggest that a complex neural network including parts of the posterior parietal lobe and midbrain are involved in covert…

Creating Accessible Science Museums with User-Activated Environmental Audio Beacons (Ping!)

ERIC Educational Resources Information Center

Landau, Steven; Wiener, William; Naghshineh, Koorosh; Giusti, Ellen

2005-01-01

In 2003, Touch Graphics Company carried out research on a new invention that promises to improve accessibility to science museums for visitors who are visually impaired. The system, nicknamed Ping!, allows users to navigate an exhibit area, listen to audio descriptions, and interact with exhibits using a cell phone-based interface. The system…

Attentional modulation of cell-class specific gamma-band synchronization in awake monkey area V4

PubMed Central

Vinck, Martin; Womelsdorf, Thilo; Buffalo, Elizabeth A.; Desimone, Robert; Fries, Pascal

2013-01-01

Summary Selective visual attention is subserved by selective neuronal synchronization, entailing precise orchestration among excitatory and inhibitory cells. We tentatively identified these as broad (BS) and narrow spiking (NS) cells and analyzed their synchronization to the local field potential in two macaque monkeys performing a selective visual attention task. Across cells, gamma phases scattered widely but were unaffected by stimulation or attention. During stimulation, NS cells lagged BS cells on average by ~60° and gamma synchronized twice as strongly. Attention enhanced and reduced the gamma locking of strongly and weakly activated cells, respectively. During a pre-stimulus attentional cue period, BS cells showed weak gamma synchronization, while NS cells gamma synchronized as strongly as with visual stimulation. These analyses reveal the cell-type specific dynamics of the gamma cycle in macaque visual cortex and suggest that attention affects neurons differentially depending on cell type and activation level. PMID:24267656

Precision Cut Mouse Lung Slices to Visualize Live Pulmonary Dendritic Cells

PubMed Central

Lyons-Cohen, Miranda R.; Thomas, Seddon Y.; Cook, Donald N.; Nakano, Hideki

2017-01-01

SHORT ABSTRACT We describe a method for generating precision-cut lung slices (PCLS) and immunostaining them to visualize the localization of various immune cell types in the lung. Our protocol can be extended to visualize the location and function of many different cell types under a variety of conditions. LONG ABSTRACT Inhalation of allergens and pathogens elicits multiple changes in a variety of immune cell types in the lung. Flow cytometry is a powerful technique for quantitative analysis of cell surface proteins on immune cells, but it provides no information on the localization and migration patterns of these cells within the lung. Similarly, in vitro chemotaxis assays can be performed to study the potential of cells to respond to chemotactic factors in vitro, but these assays do not reproduce the complex environment of the intact lung. In contrast to these aforementioned techniques, the location of individual cell types within the lung can be readily visualized by generating precision-cut lung slices (PCLS), staining them with commercially available, fluorescently tagged antibodies, and visualizing the sections by confocal microscopy. PCLS can be used for both live and fixed lung tissue, and the slices can encompass areas as large as a cross section of an entire lobe. We have used this protocol to successfully visualize the location of a wide variety of cell types in the lung, including distinct types of dendritic cells, macrophages, neutrophils, T cells and B cells, as well as structural cells such as lymphatic, endothelial, and epithelial cells. The ability to visualize cellular interactions, such as those between dendritic cells and T cells, in live, three-dimensional lung tissue, can reveal how cells move within the lung and interact with one another at steady state and during inflammation. Thus, when used in combination with other procedures, such as flow cytometry and quantitative PCR, PCLS can contribute to a comprehensive understanding of cellular events that underlie allergic and inflammatory diseases of the lung. PMID:28448013

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.

PubMed

Guyon, Laurent; Lajaunie, Christian; Fer, Frédéric; Bhajun, Ricky; Sulpice, Eric; Pinna, Guillaume; Campalans, Anna; Radicella, J Pablo; Rouillier, Philippe; Mary, Mélissa; Combe, Stéphanie; Obeid, Patricia; Vert, Jean-Philippe; Gidrol, Xavier

2015-09-18

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection.

Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays

PubMed Central

Guyon, Laurent; Lajaunie, Christian; fer, Frédéric; bhajun, Ricky; sulpice, Eric; pinna, Guillaume; campalans, Anna; radicella, J. Pablo; rouillier, Philippe; mary, Mélissa; combe, Stéphanie; obeid, Patricia; vert, Jean-Philippe; gidrol, Xavier

2015-01-01

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection. PMID:26382112

[Application of digital pathology tools. An unusual case of non-Hodgkin lymphoma].

PubMed

Meyer, A-S K; Dallenbach, F E; Lienert, G; Möller, P; Lennerz, J K

2012-11-01

Currently, lymphoma diagnosis is based on a combination of morphology, immunophenotyping, and molecular testing. Using the example of an unusual case of malignant non-Hodgkin lymphoma, we show that improved visualization using digital pathology contributes to the convergence of these complementary diagnostic modalities. A 45-year-old woman presented with skin rash and cervical lymphadenopathy. Histological workup of an excised lymph node showed loss of normal architecture with diffuse infiltration and increased mitotic activity. Immunohistochemistry for CD3/CD5 showed atypical arrangement and infiltration of a T-cell population that dominated over regionally dense, MUM1-positive plasmacellular infiltrates. Expanded CD21/CD23-positive meshworks of follicular dendritic cells were present within and between regressed follicles and the T-cell infiltrate; staining for CD56 and cyclin-D1 was negative. Quantification of Ki-67 staining within the T-, B- and plasmacellular compartments was achieved by digital image conversion, overlay and subsequent quantification algorithms that revealed proliferation within more than 60% of T-cells, over 50% of plasma cells and only 20% of B-cells. Clonality analysis by PCR revealed monoclonal rearrangement for both T-cell receptor gamma chains and immunoglobulin heavy chains. Taken together, we present an unusual combination of an angioimmunoblastic T-cell lymphoma (AITL) and simultaneous plasmacellular lymphoma. This report demonstrates how application of modern tools of digital pathology can visually integrate unusual morphological and molecular findings.

Dynamic focus optical coherence tomography: feasibility for improved basal cell carcinoma investigation

NASA Astrophysics Data System (ADS)

Nasiri-Avanaki, M. R.; Aber, Ahmed; Hojjatoleslami, S. A.; Sira, Mano; Schofield, John B.; Jones, Carole; Podoleanu, A. Gh.

2012-03-01

Basal cell carcinoma (BCC) is the most common form of skin cancer. To improve the diagnostic accuracy, additional non-invasive methods of making a preliminary diagnosis have been sought. We have implemented an En-Face optical coherence tomography (OCT) for this study in which the dynamic focus was integrated into it. With the dynamic focus scheme, the coherence gate moves synchronously with the peak of confocal gate determined by the confocal interface optics. The transversal resolution is then conserved throughout the depth range and an enhanced signal is returned from all depths. The Basal Cell Carcinoma specimens were obtained from the eyelid a patient. The specimens under went analysis by DF-OCT imaging. We searched for remarkable features that were visualized by OCT and compared these findings with features presented in the histology slices.

Combining Perfluorocarbon and Superparamagnetic Iron-oxide Cell Labeling for Improved and Expanded Applications of Cellular MRI

PubMed Central

Hitchens, T. Kevin; Liu, Li; Foley, Lesley M.; Simplaceanu, Virgil; Ahrens, Eric T.; Ho, Chien

2014-01-01

Purpose The ability to detect the migration of cells in living organisms is fundamental in understanding biological processes and important for the development of novel cell-based therapies to treat disease. MRI can be used to detect the migration of cells labeled with superparamagnetic iron-oxide (SPIO) or perfluorocarbon (PFC) agents. In this study, we explored combining these two cell-labeling approaches to overcome current limitations and enable new applications for cellular MRI. Methods We characterized 19F-NMR relaxation properties of PFC-labeled cells in the presence of SPIO and imaged cells both ex vivo and in vivo in a rodent inflammation model to demonstrate selective visualization of cell populations. Results We show that with UTE3D, RARE and FLASH 19F images one can uniquely identify PFC-labeled cells, co-localized PFC- and SPIO-labeled cells, and PFC/SPIO co-labeled cells. Conclusion This new methodology has the ability to improve and expand applications of MRI cell tracking. Combining PFC and SPIO strategies can potentially provide a method to quench PFC signal transferred from dead cells to macrophages, thereby eliminating false positives. In addition, combining these techniques could also be used to track two cell types simultaneously and probe cell-cell proximity in vivo with MRI. PMID:24478194

AHL signaling molecules with a large acyl chain enhance biofilm formation on sulfur and metal sulfides by the bioleaching bacterium Acidithiobacillus ferrooxidans.

PubMed

González, Alex; Bellenberg, Sören; Mamani, Sigde; Ruiz, Lina; Echeverría, Alex; Soulère, Laurent; Doutheau, Alain; Demergasso, Cecilia; Sand, Wolfgang; Queneau, Yves; Vera, Mario; Guiliani, Nicolas

2013-04-01

Biofilm formation plays a pivotal role in bioleaching activities of bacteria in both industrial and natural environments. Here, by visualizing attached bacterial cells on energetic substrates with different microscopy techniques, we obtained the first direct evidence that it is possible to positively modulate biofilm formation of the extremophilic bacterium Acidithiobacillus ferrooxidans on sulfur and pyrite surfaces by using Quorum Sensing molecules of the N-acylhomoserine lactone type (AHLs). Our results revealed that AHL-signaling molecules with a long acyl chain (12 or 14 carbons) increased the adhesion of A. ferrooxidans cells to these substrates. In addition, Card-Fish experiments demonstrated that C14-AHL improved the adhesion of indigenous A. ferrooxidans cells from a mixed bioleaching community to pyrite. Finally, we demonstrated that this improvement of cell adhesion is correlated with an increased production of extracellular polymeric substances. Our results open up a promising means to develop new strategies for the improvement of bioleaching efficiency and metal recovery, which could also be used to control environmental damage caused by acid mine/rock drainage.

Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool

PubMed Central

2013-01-01

Background System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes/proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries. While many enrichment analysis tools and gene-set libraries databases have been developed, there is still room for improvement. Results Here, we present Enrichr, an integrative web-based and mobile software application that includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. We applied Enrichr to analyze nine cancer cell lines by comparing their enrichment signatures to the enrichment signatures of matched normal tissues. We observed a common pattern of up regulation of the polycomb group PRC2 and enrichment for the histone mark H3K27me3 in many cancer cell lines, as well as alterations in Toll-like receptor and interlukin signaling in K562 cells when compared with normal myeloid CD33+ cells. Such analyses provide global visualization of critical differences between normal tissues and cancer cell lines but can be applied to many other scenarios. Conclusions Enrichr is an easy to use intuitive enrichment analysis web-based tool providing various types of visualization summaries of collective functions of gene lists. Enrichr is open source and freely available online at: http://amp.pharm.mssm.edu/Enrichr. PMID:23586463

Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool.

PubMed

Chen, Edward Y; Tan, Christopher M; Kou, Yan; Duan, Qiaonan; Wang, Zichen; Meirelles, Gabriela Vaz; Clark, Neil R; Ma'ayan, Avi

2013-04-15

System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes/proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries. While many enrichment analysis tools and gene-set libraries databases have been developed, there is still room for improvement. Here, we present Enrichr, an integrative web-based and mobile software application that includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. We applied Enrichr to analyze nine cancer cell lines by comparing their enrichment signatures to the enrichment signatures of matched normal tissues. We observed a common pattern of up regulation of the polycomb group PRC2 and enrichment for the histone mark H3K27me3 in many cancer cell lines, as well as alterations in Toll-like receptor and interlukin signaling in K562 cells when compared with normal myeloid CD33+ cells. Such analyses provide global visualization of critical differences between normal tissues and cancer cell lines but can be applied to many other scenarios. Enrichr is an easy to use intuitive enrichment analysis web-based tool providing various types of visualization summaries of collective functions of gene lists. Enrichr is open source and freely available online at: http://amp.pharm.mssm.edu/Enrichr.

Retinal Structure Measurements as Inclusion Criteria for Stem Cell-Based Therapies of Retinal Degenerations.

PubMed

Jacobson, Samuel G; Matsui, Rodrigo; Sumaroka, Alexander; Cideciyan, Artur V

2016-04-01

We reviewed and illustrated the most optimal retinal structural measurements to make in stem cell clinical trials. Optical coherence tomography (OCT) and autofluorescence (AF) imaging were used to evaluate patients with severe visual loss from nonsyndromic and syndromic retinitis pigmentosa (RP), ABCA4-Stargardt disease, and nonneovascular age-related macular degeneration (AMD). Outer nuclear layer (ONL), rod outer segment (ROS) layer, inner retina, ganglion cell layer (GCL), and nerve fiber layer (NFL) thicknesses were quantified. All patients had severely reduced visual acuities. Retinitis pigmentosa patients had limited visual fields; maculopathy patients had central scotomas with retained peripheral function. For the forms of RP illustrated, there was detectable albeit severely reduced ONL across the scanned retina, and normal or hyperthick GCL and NFL. Maculopathy patients had no measurable ONL centrally; it became detectable with eccentricity. Some maculopathy patients showed unexpected GCL losses. Autofluorescence imaging illustrated central losses of RPE integrity. A hypothetical scheme to relate patient data with different phases of retinal remodeling in animal models of retinal degeneration was presented. Stem cell science is advancing, but it is not too early to open the discussion of criteria for patient selection and monitoring. Available clinical tools, such as OCT and AF imaging, can provide inclusion/exclusion criteria and robust objective outcomes. Accepting that early trials may not lead to miraculous cures, we should be prepared to know why-scientifically and clinically-so we can improve subsequent trials. We also must determine if retinal remodeling is an impediment to efficacy.

Coherent motion threshold measurements for M-cell deficit differ for above- and below-average readers.

PubMed

Solan, Harold A; Hansen, Peter C; Shelley-Tremblay, John; Ficarra, Anthony

2003-11-01

Research during the past 20 years has influenced the management of diagnosis and treatment of children identified as having learning-related vision problems. The intent of this study is to determine whether coherent motion threshold testing can distinguish better-than-average non-disabled (ND) readers from those who are moderately reading disabled (RD) among sixth-grade students. A sample of 23 better-than-average non-disabled readers (> or = 80th percentile) and 27 moderately disabled readers (< or = 32nd percentile) were identified using a standardized reading comprehension test. Each participant was tested for coherent motion threshold. Previous psychophysical and fMRI research with adults suggests that coherent motion threshold is a valid measure of magnocellular (M-cell) integrity. The average of two coherent motion threshold trials was significantly greater for moderately reading disabled subjects than for above-average readers (p < 0.01). The mean threshold percentage of dots required to observe lateral motion was 9.2% for moderately reading disabled readers and 4.6% for superior readers (p = 0.001). The outcome of this preliminary study provides an efficient procedure to identify sixth-grade students whose reading disability may be associated with an M-cell deficit. Our previous investigations involving visual processing, visual attention, and oculomotor therapy have resulted in significant improvements in reading comprehension, visual attention, and eye movements. It remains to be demonstrated whether vision therapy has an impact on the M-cell deficit, as measured with coherent motion threshold testing for moderately disabled readers.

Journey to the centre of the cell: Virtual reality immersion into scientific data.

PubMed

Johnston, Angus P R; Rae, James; Ariotti, Nicholas; Bailey, Benjamin; Lilja, Andrew; Webb, Robyn; Ferguson, Charles; Maher, Sheryl; Davis, Thomas P; Webb, Richard I; McGhee, John; Parton, Robert G

2018-02-01

Visualization of scientific data is crucial not only for scientific discovery but also to communicate science and medicine to both experts and a general audience. Until recently, we have been limited to visualizing the three-dimensional (3D) world of biology in 2 dimensions. Renderings of 3D cells are still traditionally displayed using two-dimensional (2D) media, such as on a computer screen or paper. However, the advent of consumer grade virtual reality (VR) headsets such as Oculus Rift and HTC Vive means it is now possible to visualize and interact with scientific data in a 3D virtual world. In addition, new microscopic methods provide an unprecedented opportunity to obtain new 3D data sets. In this perspective article, we highlight how we have used cutting edge imaging techniques to build a 3D virtual model of a cell from serial block-face scanning electron microscope (SBEM) imaging data. This model allows scientists, students and members of the public to explore and interact with a "real" cell. Early testing of this immersive environment indicates a significant improvement in students' understanding of cellular processes and points to a new future of learning and public engagement. In addition, we speculate that VR can become a new tool for researchers studying cellular architecture and processes by populating VR models with molecular data. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study

PubMed Central

Limoli, Paolo Giuseppe; Limoli, Celeste; Vingolo, Enzo Maria; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

2016-01-01

Background The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. Results 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. Methods Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (μm) and group B with RTA equal to or more than 250 μm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). Conclusions The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity. PMID:27391437

Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study.

PubMed

Limoli, Paolo Giuseppe; Limoli, Celeste; Vingolo, Enzo Maria; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

2016-07-26

The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (µm) and group B with RTA equal to or more than 250 µm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity.

Hybrid image representation learning model with invariant features for basal cell carcinoma detection

NASA Astrophysics Data System (ADS)

Arevalo, John; Cruz-Roa, Angel; González, Fabio A.

2013-11-01

This paper presents a novel method for basal-cell carcinoma detection, which combines state-of-the-art methods for unsupervised feature learning (UFL) and bag of features (BOF) representation. BOF, which is a form of representation learning, has shown a good performance in automatic histopathology image classi cation. In BOF, patches are usually represented using descriptors such as SIFT and DCT. We propose to use UFL to learn the patch representation itself. This is accomplished by applying a topographic UFL method (T-RICA), which automatically learns visual invariance properties of color, scale and rotation from an image collection. These learned features also reveals these visual properties associated to cancerous and healthy tissues and improves carcinoma detection results by 7% with respect to traditional autoencoders, and 6% with respect to standard DCT representations obtaining in average 92% in terms of F-score and 93% of balanced accuracy.

Stem Cell Therapy for Treatment of Ocular Disorders

PubMed Central

Sivan, Padma Priya; Syed, Sakinah; Mok, Pooi-Ling; Higuchi, Akon; Murugan, Kadarkarai; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Awang Hamat, Rukman; Umezawa, Akihiro; Kumar, Suresh

2016-01-01

Sustenance of visual function is the ultimate focus of ophthalmologists. Failure of complete recovery of visual function and complications that follow conventional treatments have shifted search to a new form of therapy using stem cells. Stem cell progenitors play a major role in replenishing degenerated cells despite being present in low quantity and quiescence in our body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and differentiation. We review the processes of human eye development and address the strategies that have been exploited in an effort to regain visual function in the preclinical and clinical state. The update of clinical findings of patients receiving stem cell treatment is also presented. PMID:27293447

Seeing Cells: Teaching the Visual/Verbal Rhetoric of Biology

ERIC Educational Resources Information Center

Dinolfo, John; Heifferon, Barbara; Temesvari, Lesly A.

2007-01-01

This pilot study obtained baseline information on verbal and visual rhetorics to teach microscopy techniques to college biology majors. We presented cell images to students in cell biology and biology writing classes and then asked them to identify textual, verbal, and visual cues that support microscopy learning. Survey responses suggest that…

Macroglia-derived thrombospondin 2 regulates alterations of presynaptic proteins of retinal neurons following elevated hydrostatic pressure.

PubMed

Wang, Shuchao; Hu, Tu; Wang, Zhen; Li, Na; Zhou, Lihong; Liao, Lvshuang; Wang, Mi; Liao, Libin; Wang, Hui; Zeng, Leping; Fan, Chunling; Zhou, Hongkang; Xiong, Kun; Huang, Jufang; Chen, Dan

2017-01-01

Many studies on retinal injury and repair following elevated intraocular pressure suggest that the survival ratio of retinal neurons has been improved by various measures. However, the visual function recovery is far lower than expected. The homeostasis of retinal synapses in the visual signal pathway is the key structural basis for the delivery of visual signals. Our previous studies found that complicated changes in the synaptic structure between retinal neurons occurred much earlier than obvious degeneration of retinal ganglion cells in rat retinae. The lack of consideration of these earlier retinal synaptic changes in the rescue strategy may be partly responsible for the limited visual function recovery with the types of protective methods for retinal neurons used following elevated intraocular pressure. Thus, research on the modulatory mechanisms of the synaptic changes after elevated intraocular pressure injury may give new light to visual function rescue. In this study, we found that thrombospondin 2, an important regulator of synaptogenesis in central nervous system development, was distributed in retinal macroglia cells, and its receptor α2δ-1 was in retinal neurons. Cell cultures including mixed retinal macroglia cells/neuron cultures and retinal neuron cultures were exposed to elevated hydrostatic pressure for 2 h. The expression levels of glial fibrillary acidic protein (the marker of activated macroglia cells), thrombospondin 2, α2δ-1 and presynaptic proteins were increased following elevated hydrostatic pressure in mixed cultures, but the expression levels of postsynaptic proteins were not changed. SiRNA targeting thrombospondin 2 could decrease the upregulation of presynaptic proteins induced by the elevated hydrostatic pressure. However, in retinal neuron cultures, elevated hydrostatic pressure did not affect the expression of presynaptic or postsynaptic proteins. Rather, the retinal neuron cultures with added recombinant thrombospondin 2 protein upregulated the level of presynaptic proteins. Finally, gabapentin decreased the expression of presynaptic proteins in mixed cultures by blocking the interaction of thrombospondin 2 and α2δ-1. Taken together, these results indicate that activated macroglia cells may participate in alterations of presynaptic proteins of retinal neurons following elevated hydrostatic pressure, and macroglia-derived thrombospondin 2 may modulate these changes via binding to its neuronal receptor α2δ-1.

Ocular chemical injuries and their management.

PubMed

Singh, Parul; Tyagi, Manoj; Kumar, Yogesh; Gupta, K K; Sharma, P D

2013-05-01

Chemical burns represent potentially blinding ocular injuries and constitute a true ocular emergency requiring immediate assessment and initiation of treatment. The majority of victims are young and exposure occurs at home, work place and in association with criminal assaults. Alkali injuries occur more frequently than acid injuries. Chemical injuries of the eye produce extensive damage to the ocular surface epithelium, cornea, anterior segment and limbal stem cells resulting in permanent unilateral or bilateral visual impairment. Emergency management if appropriate may be single most important factor in determining visual outcome. This article reviews the emergency management and newer techniques to improve the prognosis of patients with chemical injuries.

The Effects of Forest Therapy on Coping with Chronic Widespread Pain: Physiological and Psychological Differences between Participants in a Forest Therapy Program and a Control Group.

PubMed

Han, Jin-Woo; Choi, Han; Jeon, Yo-Han; Yoon, Chong-Hyeon; Woo, Jong-Min; Kim, Won

2016-02-24

This study aimed to investigate the effects of a two-day forest therapy program on individuals with chronic widespread pain. Sixty one employees of a public organization providing building and facilities management services within the Seoul Metropolitan area participated in the study. Participants were assigned to an experimental group (n = 33) who participated in a forest therapy program or a control group (n = 28) on a non-random basis. Pre- and post-measures of heart rate variability (HRV), Natural Killer cell (NK cell) activity, self-reported pain using the visual analog scale (VAS), depression level using the Beck Depression Inventory (BDI), and health-related quality of life measures using the EuroQol Visual Analog Scale (EQ-VAS) were collected in both groups. The results showed that participants in the forest therapy group, as compared to the control group, showed physiological improvement as indicated by a significant increase in some measures of HRV and an increase in immune competence as indicated by NK cell activity. Participants in the forest therapy group also reported significant decreases in pain and depression, and a significant improvement in health-related quality of life. These results support the hypothesis that forest therapy is an effective intervention to relieve pain and associated psychological and physiological symptoms in individuals with chronic widespread pain.

Laser Capture Microdissection in the Genomic and Proteomic Era: Targeting the Genetic Basis of Cancer

PubMed Central

Domazet, Barbara; MacLennan, Gregory T.; Lopez-Beltran, Antonio; Montironi, Rodolfo; Cheng, Liang

2008-01-01

The advent of new technologies has enabled deeper insight into processes atsubcellular levels, which will ultimately improve diagnostic procedures and patient outcome. Thanks to cell enrichment methods, it is now possible to study cells in their native environment. This has greatly contributed to a rapid growth in several areas, such as gene expression analysis, proteomics, and metabolonomics. Laser capture microdissection (LCM) as a method of procuring subpopulations of cells under direct visual inspection is playing an important role in these areas. This review provides an overview of existing LCM technology and its downstream applications in genomics, proteomics, diagnostics and therapy. PMID:18787684

Laser capture microdissection in the genomic and proteomic era: targeting the genetic basis of cancer.

PubMed

Domazet, Barbara; Maclennan, Gregory T; Lopez-Beltran, Antonio; Montironi, Rodolfo; Cheng, Liang

2008-03-15

The advent of new technologies has enabled deeper insight into processes at subcellular levels, which will ultimately improve diagnostic procedures and patient outcome. Thanks to cell enrichment methods, it is now possible to study cells in their native environment. This has greatly contributed to a rapid growth in several areas, such as gene expression analysis, proteomics, and metabolonomics. Laser capture microdissection (LCM) as a method of procuring subpopulations of cells under direct visual inspection is playing an important role in these areas. This review provides an overview of existing LCM technology and its downstream applications in genomics, proteomics, diagnostics and therapy.

A Neural Theory of Visual Attention: Bridging Cognition and Neurophysiology

ERIC Educational Resources Information Center

Bundesen, Claus; Habekost, Thomas; Kyllingsbaek, Soren

2005-01-01

A neural theory of visual attention (NTVA) is presented. NTVA is a neural interpretation of C. Bundesen's (1990) theory of visual attention (TVA). In NTVA, visual processing capacity is distributed across stimuli by dynamic remapping of receptive fields of cortical cells such that more processing resources (cells) are devoted to behaviorally…

Micro-optical coherence tomography of the mammalian cochlea

PubMed Central

Iyer, Janani S.; Batts, Shelley A.; Chu, Kengyeh K.; Sahin, Mehmet I.; Leung, Hui Min; Tearney, Guillermo J.; Stankovic, Konstantina M.

2016-01-01

The mammalian cochlea has historically resisted attempts at high-resolution, non-invasive imaging due to its small size, complex three-dimensional structure, and embedded location within the temporal bone. As a result, little is known about the relationship between an individual’s cochlear pathology and hearing function, and otologists must rely on physiological testing and imaging methods that offer limited resolution to obtain information about the inner ear prior to performing surgery. Micro-optical coherence tomography (μOCT) is a non-invasive, low-coherence interferometric imaging technique capable of resolving cellular-level anatomic structures. To determine whether μOCT is capable of resolving mammalian intracochlear anatomy, fixed guinea pig inner ears were imaged as whole temporal bones with cochlea in situ. Anatomical structures such as the tunnel of Corti, space of Nuel, modiolus, scalae, and cell groupings were visualized, in addition to individual cell types such as neuronal fibers, hair cells, and supporting cells. Visualization of these structures, via volumetrically-reconstructed image stacks and endoscopic perspective videos, represents an improvement over previous efforts using conventional OCT. These are the first μOCT images of mammalian cochlear anatomy, and they demonstrate μOCT’s potential utility as an imaging tool in otology research. PMID:27633610

Chronic treadmill exercise in rats delicately alters the Purkinje cell structure to improve motor performance and toxin resistance in the cerebellum.

PubMed

Huang, Tung-Yi; Lin, Lung-Sheng; Cho, Keng-Chi; Chen, Shean-Jen; Kuo, Yu-Min; Yu, Lung; Wu, Fong-Sen; Chuang, Jih-Ing; Chen, Hsiun-Ing; Jen, Chauying J

2012-09-01

Although exercise usually improves motor performance, the underlying cellular changes in the cerebellum remain to be elucidated. This study aimed to investigate whether and how chronic treadmill exercise in young rats induced Purkinje cell changes to improve motor performance and rendered the cerebellum less vulnerable to toxin insults. After 1-wk familiarization of treadmill running, 6-wk-old male Wistar rats were divided into exercise and sedentary groups. The exercise group was then subjected to 8 wk of exercise training at moderate intensity. The rotarod test was carried out to evaluate motor performance. Purkinje cells in cerebellar slices were visualized by lucifer yellow labeling in single neurons and by calbindin immunostaining in groups of neurons. Compared with sedentary control rats, exercised rats not only performed better in the rotarod task, but also showed finer Purkinje cell structure (higher dendritic volume and spine density with the same dendritic field). The exercise-improved cerebellar functions were further evaluated by monitoring the long-lasting effects of intraventricular application of OX7-saporin. In the sedentary group, OX7-saporin treatment retarded the rotarod performance and induced ∼60% Purkinje cell loss in 3 wk. As a comparison, the exercise group showed much milder injuries in the cerebellum by the same toxin treatment. In conclusion, exercise training in young rats increased the dendritic density of Purkinje cells, which might play an important role in improving the motor performance. Furthermore, as Purkinje cells in the exercise group were relatively toxin resistant, the exercised rats showed good motor performance, even under toxin-treated conditions.

Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging

PubMed Central

2011-01-01

Background Stem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate in vivo. Non-invasive cell tracking can provide knowledge about mechanisms responsible for functional improvement of host tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label and visualize various cell types with magnetic resonance imaging (MRI). In this study we performed experiments designed to investigate the biological properties, including proliferation, viability and differentiation capacity of mesenchymal cells (MSCs) labeled with clinically approved SPIONs. Results Rat and mouse MSCs were isolated, cultured, and incubated with dextran-covered SPIONs (ferumoxide) alone or with poly-L-lysine (PLL) or protamine chlorhydrate for 4 or 24 hrs. Labeling efficiency was evaluated by dextran immunocytochemistry and MRI. Cell proliferation and viability were evaluated in vitro with Ki67 immunocytochemistry and live/dead assays. Ferumoxide-labeled MSCs could be induced to differentiate to adipocytes, osteocytes and chondrocytes. We analyzed ferumoxide retention in MSCs with or without mitomycin C pretreatment. Approximately 95% MSCs were labeled when incubated with ferumoxide for 4 or 24 hrs in the presence of PLL or protamine, whereas labeling of MSCs incubated with ferumoxide alone was poor. Proliferative capacity was maintained in MSCs incubated with ferumoxide and PLL for 4 hrs, however, after 24 hrs it was reduced. MSCs incubated with ferumoxide and protamine were efficiently visualized by MRI; they maintained proliferation and viability for up to 7 days and remained competent to differentiate. After 21 days MSCs pretreated with mitomycin C still showed a large number of ferumoxide-labeled cells. Conclusions The efficient and long lasting uptake and retention of SPIONs by MSCs using a protocol employing ferumoxide and protamine may be applicable to patients, since both ferumoxides and protamine are approved for human use. PMID:21542946

Allogeneic Transplantation of Müller-Derived Retinal Ganglion Cells Improves Retinal Function in a Feline Model of Ganglion Cell Depletion

PubMed Central

Becker, Silke; Eastlake, Karen; Jayaram, Hari; Jones, Megan F.; Brown, Robert A.; McLellan, Gillian J.; Charteris, David G.; Khaw, Peng T.

2016-01-01

Human Müller glia with stem cell characteristics (hMGSCs) have been shown to improve retinal function upon transplantation into rat models of retinal ganglion cell (RGC) depletion. However, their translational potential may depend upon successful engraftment and improvement of retinal function in experimental models with anatomical and functional features resembling those of the human eye. We investigated the effect of allogeneic transplantation of feline Müller glia with the ability to differentiate into cells expressing RGC markers, following ablation of RGCs by N-methyl-d-aspartate (NMDA). Unlike previous observations in the rat, transplantation of hMGSC-derived RGCs into the feline vitreous formed aggregates and elicited a severe inflammatory response without improving visual function. In contrast, allogeneic transplantation of feline MGSC (fMGSC)-derived RGCs into the vitrectomized eye improved the scotopic threshold response (STR) of the electroretinogram (ERG). Despite causing functional improvement, the cells did not attach onto the retina and formed aggregates on peripheral vitreous remnants, suggesting that vitreous may constitute a barrier for cell attachment onto the retina. This was confirmed by observations that cellular scaffolds of compressed collagen and enriched preparations of fMGSC-derived RGCs facilitated cell attachment. Although cells did not migrate into the RGC layer or the optic nerve, they significantly improved the STR and the photopic negative response of the ERG, indicative of increased RGC function. These results suggest that MGSCs have a neuroprotective ability that promotes partial recovery of impaired RGC function and indicate that cell attachment onto the retina may be necessary for transplanted cells to confer neuroprotection to the retina. Significance Müller glia with stem cell characteristics are present in the adult human retina, but they do not have regenerative ability. These cells, however, have potential for development of cell therapies to treat retinal disease. Using a feline model of retinal ganglion cell (RGC) depletion, cell grafting methods to improve RGC function have been developed. Using cellular scaffolds, allogeneic transplantation of Müller glia-derived RGC promoted cell attachment onto the retina and enhanced retinal function, as judged by improvement of the photopic negative and scotopic threshold responses of the electroretinogram. The results suggest that the improvement of RGC function observed may be ascribed to the neuroprotective ability of these cells and indicate that attachment of the transplanted cells onto the retina is required to promote effective neuroprotection. PMID:26718648

Insights from zebrafish on human pigment cell disease and treatment.

PubMed

Cooper, Cynthia D

2017-11-01

Black pigment cells, melanocytes, arise early during development from multipotent neural crest cells. Melanocytes protect human skin from DNA damaging sunrays and provide color for hair, eyes, and skin. Several disorders and diseases originate from these cells, including the deadliest skin cell cancer, melanoma. Thus, melanocytes are critical for a healthy life and for protecting humans from disease. Due to the ease of visualizing pigment cells through transparent larvae skin and conserved roles for zebrafish melanophore genes to mammalian melanocyte genes, zebrafish larvae offer a biologically relevant model for understanding pigment cell development and disease in humans. This review discusses our current knowledge of melanophore biology and how zebrafish are contributing to improving how diseases of melanocytes are understood and treated in humans. Developmental Dynamics 246:889-896, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.

PubMed

Kondo, Yuki; Nurani, Alif Meem; Saito, Chieko; Ichihashi, Yasunori; Saito, Masato; Yamazaki, Kyoko; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Fukuda, Hiroo

2016-06-01

Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. © 2016 American Society of Plant Biologists. All rights reserved.

Representation of the visual field in the primary visual area of the marmoset monkey: magnification factors, point-image size, and proportionality to retinal ganglion cell density.

PubMed

Chaplin, Tristan A; Yu, Hsin-Hao; Rosa, Marcello G P

2013-04-01

The primary visual area (V1) forms a systematic map of the visual field, in which adjacent cell clusters represent adjacent points of visual space. A precise quantification of this map is key to understanding the anatomical relationships between neurons located in different stations of the visual pathway, as well as the neural bases of visual performance in different regions of the visual field. We used computational methods to quantify the visual topography of V1 in the marmoset (Callithrix jacchus), a small diurnal monkey. The receptive fields of neurons throughout V1 were mapped in two anesthetized animals using electrophysiological recordings. Following histological reconstruction, precise 3D reconstructions of the V1 surface and recording sites were generated. We found that the areal magnification factor (M(A) ) decreases with eccentricity following a function that has the same slope as that observed in larger diurnal primates, including macaque, squirrel, and capuchin monkeys, and humans. However, there was no systematic relationship between M(A) and polar angle. Despite individual variation in the shape of V1, the relationship between M(A) and eccentricity was preserved across cases. Comparison between V1 and the retinal ganglion cell density demonstrated preferential magnification of central space in the cortex. The size of the cortical compartment activated by a punctiform stimulus decreased from the foveal representation towards the peripheral representation. Nonetheless, the relationship between the receptive field sizes of V1 cells and the density of ganglion cells suggested that each V1 cell receives information from a similar number of retinal neurons, throughout the visual field. Copyright © 2012 Wiley Periodicals, Inc.

In vivo dark-field imaging of the retinal pigment epithelium cell mosaic

PubMed Central

Scoles, Drew; Sulai, Yusufu N.; Dubra, Alfredo

2013-01-01

Non-invasive reflectance imaging of the human RPE cell mosaic is demonstrated using a modified confocal adaptive optics scanning light ophthalmoscope (AOSLO). The confocal circular aperture in front of the imaging detector was replaced with a combination of a circular aperture 4 to 16 Airy disks in diameter and an opaque filament, 1 or 3 Airy disks thick. This arrangement reveals the RPE cell mosaic by dramatically attenuating the light backscattered by the photoreceptors. The RPE cell mosaic was visualized in all 7 recruited subjects at multiple retinal locations with varying degrees of contrast and cross-talk from the photoreceptors. Various experimental settings were explored for improving the visualization of the RPE cell boundaries including: pinhole diameter, filament thickness, illumination and imaging pupil apodization, unmatched imaging and illumination focus, wavelength and polarization. None of these offered an obvious path for enhancing image contrast. The demonstrated implementation of dark-field AOSLO imaging using 790 nm light requires low light exposures relative to light safety standards and it is more comfortable for the subject than the traditional autofluorescence RPE imaging with visible light. Both these factors make RPE dark-field imaging appealing for studying mechanisms of eye disease, as well as a clinical tool for screening and monitoring disease progression. PMID:24049692

Visualization assisted by parallel processing

NASA Astrophysics Data System (ADS)

Lange, B.; Rey, H.; Vasques, X.; Puech, W.; Rodriguez, N.

2011-01-01

This paper discusses the experimental results of our visualization model for data extracted from sensors. The objective of this paper is to find a computationally efficient method to produce a real time rendering visualization for a large amount of data. We develop visualization method to monitor temperature variance of a data center. Sensors are placed on three layers and do not cover all the room. We use particle paradigm to interpolate data sensors. Particles model the "space" of the room. In this work we use a partition of the particle set, using two mathematical methods: Delaunay triangulation and Voronoý cells. Avis and Bhattacharya present these two algorithms in. Particles provide information on the room temperature at different coordinates over time. To locate and update particles data we define a computational cost function. To solve this function in an efficient way, we use a client server paradigm. Server computes data and client display this data on different kind of hardware. This paper is organized as follows. The first part presents related algorithm used to visualize large flow of data. The second part presents different platforms and methods used, which was evaluated in order to determine the better solution for the task proposed. The benchmark use the computational cost of our algorithm that formed based on located particles compared to sensors and on update of particles value. The benchmark was done on a personal computer using CPU, multi core programming, GPU programming and hybrid GPU/CPU. GPU programming method is growing in the research field; this method allows getting a real time rendering instates of a precompute rendering. For improving our results, we compute our algorithm on a High Performance Computing (HPC), this benchmark was used to improve multi-core method. HPC is commonly used in data visualization (astronomy, physic, etc) for improving the rendering and getting real-time.

Biological Dynamics Markup Language (BDML): an open format for representing quantitative biological dynamics data

PubMed Central

Kyoda, Koji; Tohsato, Yukako; Ho, Kenneth H. L.; Onami, Shuichi

2015-01-01

Motivation: Recent progress in live-cell imaging and modeling techniques has resulted in generation of a large amount of quantitative data (from experimental measurements and computer simulations) on spatiotemporal dynamics of biological objects such as molecules, cells and organisms. Although many research groups have independently dedicated their efforts to developing software tools for visualizing and analyzing these data, these tools are often not compatible with each other because of different data formats. Results: We developed an open unified format, Biological Dynamics Markup Language (BDML; current version: 0.2), which provides a basic framework for representing quantitative biological dynamics data for objects ranging from molecules to cells to organisms. BDML is based on Extensible Markup Language (XML). Its advantages are machine and human readability and extensibility. BDML will improve the efficiency of development and evaluation of software tools for data visualization and analysis. Availability and implementation: A specification and a schema file for BDML are freely available online at http://ssbd.qbic.riken.jp/bdml/. Contact: sonami@riken.jp Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:25414366

Biological Dynamics Markup Language (BDML): an open format for representing quantitative biological dynamics data.

PubMed

Kyoda, Koji; Tohsato, Yukako; Ho, Kenneth H L; Onami, Shuichi

2015-04-01

Recent progress in live-cell imaging and modeling techniques has resulted in generation of a large amount of quantitative data (from experimental measurements and computer simulations) on spatiotemporal dynamics of biological objects such as molecules, cells and organisms. Although many research groups have independently dedicated their efforts to developing software tools for visualizing and analyzing these data, these tools are often not compatible with each other because of different data formats. We developed an open unified format, Biological Dynamics Markup Language (BDML; current version: 0.2), which provides a basic framework for representing quantitative biological dynamics data for objects ranging from molecules to cells to organisms. BDML is based on Extensible Markup Language (XML). Its advantages are machine and human readability and extensibility. BDML will improve the efficiency of development and evaluation of software tools for data visualization and analysis. A specification and a schema file for BDML are freely available online at http://ssbd.qbic.riken.jp/bdml/. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.

Transplantation of reprogrammed embryonic stem cells improves visual function in a mouse model for retinitis pigmentosa.

PubMed

Wang, Nan-Kai; Tosi, Joaquin; Kasanuki, Jennifer Mie; Chou, Chai Lin; Kong, Jian; Parmalee, Nancy; Wert, Katherine J; Allikmets, Rando; Lai, Chi-Chun; Chien, Chung-Liang; Nagasaki, Takayuki; Lin, Chyuan-Sheng; Tsang, Stephen H

2010-04-27

To study whether C57BL/6J-Tyr/J (C2J) mouse embryonic stem (ES) cells can differentiate into retinal pigment epithelial (RPE) cells in vitro and then restore retinal function in a model for retinitis pigmentosa: Rpe65/Rpe65 C57BL6 mice. Yellow fluorescent protein (YFP)-labeled C2J ES cells were induced to differentiate into RPE-like structures on PA6 feeders. RPE-specific markers are expressed from differentiated cells in vitro. After differentiation, ES cell-derived RPE-like cells were transplanted into the subretinal space of postnatal day 5 Rpe65/Rpe65 mice. Live imaging of YFP-labeled C2J ES cells demonstrated survival of the graft. Electroretinograms (ERGs) were performed on transplanted mice to evaluate the functional outcome of transplantation. RPE-like cells derived from ES cells sequentially express multiple RPE-specific markers. After transplantation, YFP-labeled cells can be tracked with live imaging for as long as 7 months. Although more than half of the mice were complicated with retinal detachments or tumor development, one fourth of the mice showed increased electroretinogram responses in the transplanted eyes. Rpe65/Rpe65 mice transplanted with RPE-like cells showed significant visual recovery during a 7-month period, whereas those injected with saline, PA6 feeders, or undifferentiated ES cells showed no rescue. ES cells can differentiate, morphologically, and functionally, into RPE-like cells. Based on these findings, differentiated ES cells have the potential for the development of new therapeutic approaches for RPE-specific diseases such as certain forms of retinitis pigmentosa and macular degeneration. Nevertheless, stringent control of retinal detachment and teratoma development will be necessary before initiation of treatment trials.

Virally delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness

PubMed Central

Doroudchi, M Mehdi; Greenberg, Kenneth P; Liu, Jianwen; Silka, Kimberly A; Boyden, Edward S; Lockridge, Jennifer A; Arman, A Cyrus; Janani, Ramesh; Boye, Shannon E; Boye, Sanford L; Gordon, Gabriel M; Matteo, Benjamin C; Sampath, Alapakkam P; Hauswirth, William W; Horsager, Alan

2011-01-01

Previous work established retinal expression of channelrhodopsin-2 (ChR2), an algal cation channel gated by light, restored physiological and behavioral visual responses in otherwise blind rd1 mice. However, a viable ChR2-based human therapy must meet several key criteria: (i) ChR2 expression must be targeted, robust, and long-term, (ii) ChR2 must provide long-term and continuous therapeutic efficacy, and (iii) both viral vector delivery and ChR2 expression must be safe. Here, we demonstrate the development of a clinically relevant therapy for late stage retinal degeneration using ChR2. We achieved specific and stable expression of ChR2 in ON bipolar cells using a recombinant adeno-associated viral vector (rAAV) packaged in a tyrosine-mutated capsid. Targeted expression led to ChR2-driven electrophysiological ON responses in postsynaptic retinal ganglion cells and significant improvement in visually guided behavior for multiple models of blindness up to 10 months postinjection. Light levels to elicit visually guided behavioral responses were within the physiological range of cone photoreceptors. Finally, chronic ChR2 expression was nontoxic, with transgene biodistribution limited to the eye. No measurable immune or inflammatory response was observed following intraocular vector administration. Together, these data indicate that virally delivered ChR2 can provide a viable and efficacious clinical therapy for photoreceptor disease-related blindness. PMID:21505421

Visual Field Defects and Retinal Ganglion Cell Losses in Human Glaucoma Patients

PubMed Central

Harwerth, Ronald S.; Quigley, Harry A.

2007-01-01

Objective The depth of visual field defects are correlated with retinal ganglion cell densities in experimental glaucoma. This study was to determine whether a similar structure-function relationship holds for human glaucoma. Methods The study was based on retinal ganglion cell densities and visual thresholds of patients with documented glaucoma (Kerrigan-Baumrind, et al.) The data were analyzed by a model that predicted ganglion cell densities from standard clinical perimetry, which were then compared to histologic cell counts. Results The model, without free parameters, produced accurate and relatively precise quantification of ganglion cell densities associated with visual field defects. For 437 sets of data, the unity correlation for predicted vs. measured cell densities had a coefficient of determination of 0.39. The mean absolute deviation of the predicted vs. measured values was 2.59 dB, the mean and SD of the distribution of residual errors of prediction was -0.26 ± 3.22 dB. Conclusions Visual field defects by standard clinical perimetry are proportional to neural losses caused by glaucoma. Clinical Relevance The evidence for quantitative structure-function relationships provides a scientific basis of interpreting glaucomatous neuropathy from visual thresholds and supports the application of standard perimetry to establish the stage of the disease. PMID:16769839

Visual receptive field properties of cells in the optic tectum of the archer fish.

PubMed

Ben-Tov, Mor; Kopilevich, Ivgeny; Donchin, Opher; Ben-Shahar, Ohad; Giladi, Chen; Segev, Ronen

2013-08-01

The archer fish is well known for its extreme visual behavior in shooting water jets at prey hanging on vegetation above water. This fish is a promising model in the study of visual system function because it can be trained to respond to artificial targets and thus to provide valuable psychophysical data. Although much behavioral data have indeed been collected over the past two decades, little is known about the functional organization of the main visual area supporting this visual behavior, namely, the fish optic tectum. In this article we focus on a fundamental aspect of this functional organization and provide a detailed analysis of receptive field properties of cells in the archer fish optic tectum. Using extracellular measurements to record activities of single cells, we first measure their retinotectal mapping. We then determine their receptive field properties such as size, selectivity for stimulus direction and orientation, tuning for spatial frequency, and tuning for temporal frequency. Finally, on the basis of all these measurements, we demonstrate that optic tectum cells can be classified into three categories: orientation-tuned cells, direction-tuned cells, and direction-agnostic cells. Our results provide an essential basis for future investigations of information processing in the archer fish visual system.

Role of feedforward geniculate inputs in the generation of orientation selectivity in the cat's primary visual cortex

PubMed Central

Viswanathan, Sivaram; Jayakumar, Jaikishan; Vidyasagar, Trichur R

2011-01-01

Abstract Neurones of the mammalian primary visual cortex have the remarkable property of being selective for the orientation of visual contours. It has been controversial whether the selectivity arises from intracortical mechanisms, from the pattern of afferent connectivity from lateral geniculate nucleus (LGN) to cortical cells or from the sharpening of a bias that is already present in the responses of many geniculate cells. To investigate this, we employed a variation of an electrical stimulation protocol in the LGN that has been claimed to suppress intracortical inputs and isolate the raw geniculocortical input to a striate cortical cell. Such stimulation led to a sharpening of the orientation sensitivity of geniculate cells themselves and some broadening of cortical orientation selectivity. These findings are consistent with the idea that non-specific inhibition of the signals from LGN cells which exhibit an orientation bias can generate the sharp orientation selectivity of primary visual cortical cells. This obviates the need for an excitatory convergence from geniculate cells whose receptive fields are arranged along a row in visual space as in the classical model and provides a framework for orientation sensitivity originating in the retina and getting sharpened through inhibition at higher levels of the visual pathway. PMID:21486788

Pineal Photoreceptor Cells Are Required for Maintaining the Circadian Rhythms of Behavioral Visual Sensitivity in Zebrafish

PubMed Central

Li, Xinle; Montgomery, Jake; Cheng, Wesley; Noh, Jung Hyun; Hyde, David R.; Li, Lei

2012-01-01

In non-mammalian vertebrates, the pineal gland functions as the central pacemaker that regulates the circadian rhythms of animal behavior and physiology. We generated a transgenic zebrafish line [Tg(Gnat2:gal4-VP16/UAS:nfsB-mCherry)] in which the E. coli nitroreductase is expressed in pineal photoreceptor cells. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells. During aging, the expression of the transgene in retinal photoreceptor cells gradually diminishes. By 8 months of age, the Gnat2 promoter-driven nitroreductase is no longer expressed in retinal photoreceptor cells, but its expression in pineal photoreceptor cells persists. This provides a tool for selective ablation of pineal photoreceptor cells, i.e., by treatments with metronidazole. In the absence of pineal photoreceptor cells, the behavioral visual sensitivity of the fish remains unchanged; however, the circadian rhythms of rod and cone sensitivity are diminished. Brief light exposures restore the circadian rhythms of behavioral visual sensitivity. Together, the data suggest that retinal photoreceptor cells respond to environmental cues and are capable of entraining the circadian rhythms of visual sensitivity; however, they are insufficient for maintaining the rhythms. Cellular signals from the pineal photoreceptor cells may be required for maintaining the circadian rhythms of visual sensitivity. PMID:22815753

Perceptual learning in children with visual impairment improves near visual acuity.

PubMed

Huurneman, Bianca; Boonstra, F Nienke; Cox, Ralf F A; van Rens, Ger; Cillessen, Antonius H N

2013-09-17

This study investigated whether visual perceptual learning can improve near visual acuity and reduce foveal crowding effects in four- to nine-year-old children with visual impairment. Participants were 45 children with visual impairment and 29 children with normal vision. Children with visual impairment were divided into three groups: a magnifier group (n = 12), a crowded perceptual learning group (n = 18), and an uncrowded perceptual learning group (n = 15). Children with normal vision also were divided in three groups, but were measured only at baseline. Dependent variables were single near visual acuity (NVA), crowded NVA, LH line 50% crowding NVA, number of trials, accuracy, performance time, amount of small errors, and amount of large errors. Children with visual impairment trained during six weeks, two times per week, for 30 minutes (12 training sessions). After training, children showed significant improvement of NVA in addition to specific improvements on the training task. The crowded perceptual learning group showed the largest acuity improvements (1.7 logMAR lines on the crowded chart, P < 0.001). Only the children in the crowded perceptual learning group showed improvements on all NVA charts. Children with visual impairment benefit from perceptual training. While task-specific improvements were observed in all training groups, transfer to crowded NVA was largest in the crowded perceptual learning group. To our knowledge, this is the first study to provide evidence for the improvement of NVA by perceptual learning in children with visual impairment. (http://www.trialregister.nl number, NTR2537.).

[Efficacy of topical ketorolac for improving visual function after photocoagulation in diabetic patients with focal macular edema].

PubMed

Razo Blanco-Hernández, Dulce Milagros; Lima-Gómez, Virgilio; Asbun-Bojalil, Juan

2014-01-01

Photocoagulation reduces the incidence of visual loss in diabetic patients with focal macular edema, but it can induce it for Efficacy of topical ketorolac for improving visual function after photocoagulation in diabetic patients with focal macular edema 6 weeks after treatment and produces visual improvement in some cases. Topical ketorolac may reduce the inflammation caused by photocoagulation and improve visual outcome. To determine the efficacy of topical ketorolac for improving visual function after photocoagulation in diabetic patients with focal macular edema. An experimental, comparative, prospective, longitudinal study in diabetic patients with focal macular edema was conducted. Eyes were randomized into two groups of topical treatment for 3 weeks after photocoagulation (A: ketorolac, B: placebo). Best corrected visual acuity before and after treatment was compared in each group (paired t test), and the proportion of eyes with visual improvement was compared between groups (χ(2)). The evaluation was repeated after stratifying for initial visual acuity (≥ 0.5, < 0.5). There were 105 eyes included. In group A (n= 46) mean visual acuity changed from 0.50 to 0.58 (p= 0.003), and from 0.55 to 0.55 in group B (n= 59, p= 0.83); mean percent change was 22.3% in group A and 3.5% in group B (p= 0.03). Visual improvement was identified in 25 eyes from group A (54.3%) and 19 from group B (32.2%, p= 0.019, RR 1.65); the difference only persisted when initial visual acuity was ≥ 0.5 (10 [40%], group A, 5 [14.7%], group B, p= 0.02, RR 2.72). Topical ketorolac was more effective than placebo to improve best corrected visual acuity in diabetic patients with focal macular edema.

Application of glutaraldehyde for the staining of esterase-active cells with carboxyfluorescein diacetate.

PubMed

Morono, Yuki; Takano, Suguru; Miyanaga, Kazuhiko; Tanji, Yasunori; Unno, Hajime; Hori, Katsutoshi

2004-03-01

Staining of esterase-active bacteria with carboxyfluorescein diacetate (CFDA) has been used to evaluate the viability of various types of cell. However, the outer membrane of Gram-negative bacteria prevents CFDA from permeating into the cell. Although EDTA can increase the permeability of the outer membrane allowing CFDA to enter the cells, it was experimentally confirmed that there is still considerable difficulty in visualizing viable cells due to passive diffusion of carboxyfluorescein (CF), a hydrolyzed product of CFDA, out of the cells. We found that glutaraldehyde enhances the discriminative recognition of esterase-active Gram-negative bacteria under microscopic observation by improving the efficacy of staining. We believe the successful staining in the presence of glutaraldehyde is due to two separate effects: an increase in the permeability of CFDA into the cell and prevention of leakage of CF out of the cell.

The role of amniotic membrane extract eye drop (AMEED) in in vivo cultivation of limbal stem cells.

PubMed

Baradaran-Rafii, Alireza; Asl, Niloufar Shayan; Ebrahimi, Marzieh; Jabbehdari, Sayena; Bamdad, Shahram; Roshandel, Danial; Eslani, Medi; Momeni, Maryam

2018-01-01

Limbal stem cell transplantation (LSCT) is the definitive treatment for total limbal stem cell deficiency (LSCD). This study evaluates the anatomical and visual outcomes of a surgical technique supplemented by amniotic membrane extract eye drop (AMEED) for in vivo cultivation of limbal stem cells (LSCs). One small limbal block (2 × 1 mm) harvested from the contralateral healthy eye was transferred to the diseased eye, which had been already covered by cryopreserved amniotic membrane (N = 20). The patients were categorized into case and control groups. AMEED was administered postoperatively only for patients in the case group (N = 14). Sequential penetrating keratoplasty (PKP) was performed in 4 eyes of the case group for optical clarity. Visual acuity, epithelial healing, corneal clarity and regression of conjunctivalization/vascularization were evaluated after surgery. The corneal buttons of post-PKP eyes were evaluated for LSC markers. In the case group, the mean corrected distance visual acuity (CDVA) was 20/400 before surgery, which improved to 20/40 and 20/50 at the last follow-up in eyes with and without PKP, respectively. Epithelial defects healed in all eyes of the case group during 2 weeks after surgery. Corneal conjunctivalization/vascularization regressed dramatically in all patients of the case group 2-3 months after surgery. In PKP cases, all transplanted corneas were clear at the last follow-up. LSC markers were expressed on the surface of all trephined corneal buttons. All eyes in the control group developed persistent epithelial defect. This study suggests that amniotic membrane extract may be helpful for in vivo cultivation of limbal stem cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients.

PubMed

Liu, Yong; Chen, Shao Jun; Li, Shi Ying; Qu, Ling Hui; Meng, Xiao Hong; Wang, Yi; Xu, Hai Wei; Liang, Zhi Qing; Yin, Zheng Qin

2017-09-29

Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. However, long-term safety studies and visual assessment have not been thoroughly tested in retinitis pigmentosa patients. In our pre-clinical study, purified human fetal-derived retinal progenitor cells (RPCs) were transplanted into the diseased retina of Royal College of Surgeons (RCS) rats, a model of retinal degeneration. Based on these results, we conducted a phase I clinical trial to establish the safety and tolerability of transplantation of RPCs in eight patients with advanced retinitis pigmentosa. Patients were studied for 24 months. After RPC transplantation in RCS rats, we observed moderate recovery of vision and maintenance of the outer nuclear layer thickness. Most importantly, we did not find tumor formation or immune rejection. In the retinis pigmentosa patients given RPC injections, we also did not observe immunological rejection or tumorigenesis when immunosuppressive agents were not administered. We observed a significant improvement in visual acuity (P < 0.05) in five patients and an increase in retinal sensitivity of pupillary responses in three of the eight patients between 2 and 6 months after the transplant, but this improvement did not appear by 12 months. Our study for the first time confirmed the long-term safety and feasibility of vision repair by stem cell therapy in patients blinded by retinitis pigmentosa. WHO Trial Registration, ChiCTR-TNRC-08000193 . Retrospectively registered on 5 December 2008.

Regenerative Therapy by Suprachoroidal Cell Autograft in Dry Age-related Macular Degeneration: Preliminary In Vivo Report.

PubMed

Limoli, Paolo Giuseppe; Vingolo, Enzo Maria; Limoli, Celeste; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

2018-02-12

This study is aimed at examining whether a suprachoroidal graft of autologous cells can improve best corrected visual acuity (BCVA) and responses to microperimetry (MY) in eyes affected by dry Age-related Macular Degeneration (AMD) over time through the production and secretion of growth factors (GFs) on surrounding tissue. Patients were randomly assigned to each study group. All patients were diagnosed with dry AMD and with BCVA equal to or greater than 1 logarithm of the minimum angle of resolution (logMAR). A suprachoroidal autologous graft by Limoli Retinal Restoration Technique (LRRT) was carried out on group A, which included 11 eyes from 11 patients. The technique was performed by implanting adipocytes, adipose-derived stem cells obtained from the stromal vascular fraction, and platelets from platelet-rich plasma in the suprachoroidal space. Conversely, group B, including 14 eyes of 14 patients, was used as a control group. For each patient, diagnosis was verified by confocal scanning laser ophthalmoscope and spectral domain-optical coherence tomography (SD-OCT). In group A, BCVA improved by 0.581 to 0.504 at 90 days and to 0.376 logMAR at 180 days (+32.20%) postoperatively. Furthermore, MY test increased by 11.44 dB to 12.59 dB at 180 days. The different cell types grafted behind the choroid were able to ensure constant GF secretion in the choroidal flow. Consequently, the results indicate that visual acuity (VA) in the grafted group can increase more than in the control group after six months.

An Advanced Preclinical Mouse Model for Acute Myeloid Leukemia Using Patients' Cells of Various Genetic Subgroups and In Vivo Bioluminescence Imaging

PubMed Central

Vick, Binje; Rothenberg, Maja; Sandhöfer, Nadine; Carlet, Michela; Finkenzeller, Cornelia; Krupka, Christina; Grunert, Michaela; Trumpp, Andreas; Corbacioglu, Selim; Ebinger, Martin; André, Maya C.; Hiddemann, Wolfgang; Schneider, Stephanie; Subklewe, Marion; Metzeler, Klaus H.; Spiekermann, Karsten; Jeremias, Irmela

2015-01-01

Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease with poor outcome. Adequate model systems are required for preclinical studies to improve understanding of AML biology and to develop novel, rational treatment approaches. Xenografts in immunodeficient mice allow performing functional studies on patient-derived AML cells. We have established an improved model system that integrates serial retransplantation of patient-derived xenograft (PDX) cells in mice, genetic manipulation by lentiviral transduction, and essential quality controls by immunophenotyping and targeted resequencing of driver genes. 17/29 samples showed primary engraftment, 10/17 samples could be retransplanted and some of them allowed virtually indefinite serial transplantation. 5/6 samples were successfully transduced using lentiviruses. Neither serial transplantation nor genetic engineering markedly altered sample characteristics analyzed. Transgene expression was stable in PDX AML cells. Example given, recombinant luciferase enabled bioluminescence in vivo imaging and highly sensitive and reliable disease monitoring; imaging visualized minimal disease at 1 PDX cell in 10000 mouse bone marrow cells and facilitated quantifying leukemia initiating cells. We conclude that serial expansion, genetic engineering and imaging represent valuable tools to improve the individualized xenograft mouse model of AML. Prospectively, these advancements enable repetitive, clinically relevant studies on AML biology and preclinical treatment trials on genetically defined and heterogeneous subgroups. PMID:25793878

Smart markers for watershed-based cell segmentation.

PubMed

Koyuncu, Can Fahrettin; Arslan, Salim; Durmaz, Irem; Cetin-Atalay, Rengul; Gunduz-Demir, Cigdem

2012-01-01

Automated cell imaging systems facilitate fast and reliable analysis of biological events at the cellular level. In these systems, the first step is usually cell segmentation that greatly affects the success of the subsequent system steps. On the other hand, similar to other image segmentation problems, cell segmentation is an ill-posed problem that typically necessitates the use of domain-specific knowledge to obtain successful segmentations even by human subjects. The approaches that can incorporate this knowledge into their segmentation algorithms have potential to greatly improve segmentation results. In this work, we propose a new approach for the effective segmentation of live cells from phase contrast microscopy. This approach introduces a new set of "smart markers" for a marker-controlled watershed algorithm, for which the identification of its markers is critical. The proposed approach relies on using domain-specific knowledge, in the form of visual characteristics of the cells, to define the markers. We evaluate our approach on a total of 1,954 cells. The experimental results demonstrate that this approach, which uses the proposed definition of smart markers, is quite effective in identifying better markers compared to its counterparts. This will, in turn, be effective in improving the segmentation performance of a marker-controlled watershed algorithm.

Clinical role of early dynamic FDG-PET/CT for the evaluation of renal cell carcinoma.

PubMed

Nakajima, Reiko; Abe, Koichiro; Kondo, Tsunenori; Tanabe, Kazunari; Sakai, Shuji

2016-06-01

We studied the usefulness of early dynamic (ED) and whole-body (WB) FDG-PET/CT for the evaluation of renal cell carcinoma (RCC). One hundred patients with 107 tumours underwent kidney ED and WB FDG-PET/CT. We visually and semiquantitatively evaluated the FDG accumulation in RCCs in the ED and WB phases, and compared the accumulation values with regard to histological type (clear cell carcinoma [CCC] vs. non-clear cell carcinoma [N-CCC]), the TNM stage (high stage [3-4] vs. low stage [1-2]), the Fuhrman grade (high grade [3-4] vs. low grade [1-2]) and presence versus absence of venous (V) and lymphatic (Ly) invasion. In the ED phase, visual evaluation revealed no significant differences in FDG accumulation in terms of each item. However, the maximum standardized uptake value and tumour-to-normal tissue ratios were significantly higher in the CCCs compared to the N-CCCs (p < 0.001). In the WB phase, in contrast, significantly higher FDG accumulation (p < 0.001) was found in RCCs with a higher TNM stage, higher Furman grade, and the presence of V and Ly invasion in both the visual and the semiquantitative evaluations. ED and WB FDG-PET/CT is a useful tool for the evaluation of RCCs. • ED and WB FDG-PET/ CT helps to assess patients with RCC • ED FDG-PET/CT enabled differentiation between CCC and N-CCC • FDG accumulation in the WB phase reflects tumour aggressiveness • Management of RCC is improved by ED and WB FDG-PET/CT.

VisIO: enabling interactive visualization of ultra-scale, time-series data via high-bandwidth distributed I/O systems

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

Mitchell, Christopher J; Ahrens, James P; Wang, Jun

2010-10-15

Petascale simulations compute at resolutions ranging into billions of cells and write terabytes of data for visualization and analysis. Interactive visuaUzation of this time series is a desired step before starting a new run. The I/O subsystem and associated network often are a significant impediment to interactive visualization of time-varying data; as they are not configured or provisioned to provide necessary I/O read rates. In this paper, we propose a new I/O library for visualization applications: VisIO. Visualization applications commonly use N-to-N reads within their parallel enabled readers which provides an incentive for a shared-nothing approach to I/O, similar tomore » other data-intensive approaches such as Hadoop. However, unlike other data-intensive applications, visualization requires: (1) interactive performance for large data volumes, (2) compatibility with MPI and POSIX file system semantics for compatibility with existing infrastructure, and (3) use of existing file formats and their stipulated data partitioning rules. VisIO, provides a mechanism for using a non-POSIX distributed file system to provide linear scaling of 110 bandwidth. In addition, we introduce a novel scheduling algorithm that helps to co-locate visualization processes on nodes with the requested data. Testing using VisIO integrated into Para View was conducted using the Hadoop Distributed File System (HDFS) on TACC's Longhorn cluster. A representative dataset, VPIC, across 128 nodes showed a 64.4% read performance improvement compared to the provided Lustre installation. Also tested, was a dataset representing a global ocean salinity simulation that showed a 51.4% improvement in read performance over Lustre when using our VisIO system. VisIO, provides powerful high-performance I/O services to visualization applications, allowing for interactive performance with ultra-scale, time-series data.« less

Positive visual phenomena in space: A scientific case and a safety issue in space travel.

PubMed

Sannita, Walter G; Narici, Livio; Picozza, Piergiorgio

2006-07-01

Most astronauts on Apollo, Skylab, and MIR reported 'flashes of light' occurring in different shapes and apparently moving across the visual field, in the absence of auditory, somatosensory, or olfactory abnormal percepts. A temporal correlation with heavy nuclei or protons has been documented in space and comparable phosphenes were observed by volunteers whose eyes were exposed to accelerated heavy ions at intensities below the threshold for Cerenkov visible radiation. An interaction between heavy ions and the retina was suggested. However, the biophysics of heavy ions or protons action remains undefined, the effects on photoreceptors and neuroretina have not been differentiated, and some direct action on the visual cortex never ruled out. Phosphenes are common in migraine and are known to occur also in response to the electrical stimulation of ganglion cells (in retinas without photoreceptors), optic pathways or visual cortex, with mechanisms that bypass the chemically gated channels. Intrinsic photosensitive ganglion cells exist in the retina of teleost fish and mammals. In the hypothesis of a peculiar sensitivity to subatomic particles of the visual system, phosphenes due to the activation of processes by-passing the photoreceptors would raise questions about human safety in space. The issue is particularly relevant with experiments of increasing duration being now operative in the International Space Station (ISS) and with plans of space travel outside the geomagnetic shield. Research is in progress both in the ISS and on animal models, in the framework of the NASA/ESA actions to improve the astronauts' health in space.

Retinal constraints on orientation specificity in cat visual cortex.

PubMed

Schall, J D; Vitek, D J; Leventhal, A G

1986-03-01

Most retinal ganglion cells (Levick and Thibos, 1982) and cortical cells (Leventhal, 1983; Leventhal et al., 1984) subserving peripheral vision respond best to stimuli that are oriented radially, i.e., like the spokes of a wheel with the area centralis at the hub. We have extended this work by comparing directly the distributions of orientations represented in topographically corresponding regions of retina and visual cortex. Both central and peripheral regions were studied. The relations between the orientations of neighboring ganglion cells and the manner in which the overrepresentation of radial orientations is accommodated in the functional architecture of visual cortex were also studied. Our results are based on an analysis of the orientations of the dendritic fields of 1296 ganglion cells throughout the retina and the preferred orientations of 1389 cells located in retinotopically corresponding regions of cortical areas 17, 18, and 19 in the cat. We find that horizontal and vertical orientations are overrepresented in regions of both retina and visual cortex subserving the central 5 degrees of vision. The distributions of the orientations of retinal ganglion cells and cortical cells subserving the horizontal, vertical, and diagonal meridians outside the area centralis differ significantly. The distribution of the preferred orientations of the S (simple) cells in areas 17, 18 and 19 subserving a given part of the retina corresponds to the distribution of the dendritic field orientations of the ganglion cells in that part of retina. The distribution of the preferred orientations of C (complex) cells with narrow receptive fields in area 17 but not C cells with wide receptive fields in areas 17, 18, or 19 subserving a given part of the retina matches the distribution of the orientations of the ganglion cells in that part of retina. The orientations of all of the alpha-cells in 5-9 mm2 patches of retina along the horizontal, vertical, and oblique meridians were determined. A comparison of the orientations of neighboring cells indicates that other than a mutual tendency to be oriented radially, ganglion cells with similar orientations are not clustered in the retina. Reconstructions of electrode penetrations into regions of visual cortex representing peripheral retina indicate that columns subserving radial orientations are wider than those subserving nonradial orientations. Our results provide evidence that the distribution of the preferred orientations of simple cells in visual cortex subserving any region of the visual field matches the distribution of the orientations of the ganglion cells subserving the same region of the visual field.(ABSTRACT TRUNCATED AT 400 WORDS)

Mesenchymal stem cells and their conditioned medium improve integration of purified induced pluripotent stem cell-derived cardiomyocyte clusters into myocardial tissue.

PubMed

Rubach, Martin; Adelmann, Roland; Haustein, Moritz; Drey, Florian; Pfannkuche, Kurt; Xiao, Bing; Koester, Annette; Udink ten Cate, Floris E A; Choi, Yeong-Hoon; Neef, Klaus; Fatima, Azra; Hannes, Tobias; Pillekamp, Frank; Hescheler, Juergen; Šarić, Tomo; Brockmeier, Konrad; Khalil, Markus

2014-03-15

Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) might become therapeutically relevant to regenerate myocardial damage. Purified iPS-CMs exhibit poor functional integration into myocardial tissue. The aim of this study was to investigate whether murine mesenchymal stem cells (MSCs) or their conditioned medium (MScond) improves the integration of murine iPS-CMs into myocardial tissue. Vital or nonvital embryonic murine ventricular tissue slices were cocultured with purified clusters of iPS-CMs in combination with murine embryonic fibroblasts (MEFs), MSCs, or MScond. Morphological integration was assessed by visual scoring and functional integration by isometric force and field potential measurements. We observed a moderate morphological integration of iPS-CM clusters into vital, but a poor integration into nonvital, slices. MEFs and MSCs but not MScond improved morphological integration of CMs into nonvital slices and enabled purified iPS-CMs to confer force. Coculture of vital slices with iPS-CMs and MEFs or MSCs resulted in an improved electrical integration. A comparable improvement of electrical coupling was achieved with the cell-free MScond, indicating that soluble factors secreted by MSCs were involved in electrical coupling. We conclude that cells such as MSCs support the engraftment and adhesion of CMs, and confer force to noncontractile tissue. Furthermore, soluble factors secreted by MSCs mediate electrical coupling of purified iPS-CM clusters to myocardial tissue. These data suggest that MSCs may increase the functional engraftment and therapeutic efficacy of transplanted iPS-CMs into infarcted myocardium.

Cell structure and function in the visual cortex of the cat

PubMed Central

Kelly, J. P.; Van Essen, D. C.

1974-01-01

1. The organization of the visual cortex was studied with a technique that allows one to determine the physiology and morphology of individual cells. Micro-electrodes filled with the fluorescent dye Procion yellow were used to record intracellularly from cells in area 17 of the cat. The visual receptive field of each neurone was classified as simple, complex, or hypercomplex, and the cell was then stained by the iontophoretic injection of dye. 2. Fifty neurones were successfully examined in this way, and their structural features were compared to the varieties of cell types seen in Golgi preparations of area 17. The majority of simple units were stellate cells, whereas the majority of complex and hypercomplex units were pyramidal cells. Several neurones belonged to less common morphological types, such as double bouquet cells. Simple cells were concentrated in layer IV, hypercomplex cells in layer II + III, and complex cells in layers II + III, V and VI. 3. Electrically inexcitable cells that had high resting potentials but no impulse activity were stained and identified as glial cells. Glial cells responded to visual stimuli with slow graded depolarizations, and many of them showed a preference for a stimulus orientation similar to the optimal orientation for adjacent neurones. 4. The results show that there is a clear, but not absolute correlation between the major structural and functional classes of cells in the visual cortex. This approach, linking the physiological properties of a single cell to a given morphological type, will help in furthering our understanding of the cerebral cortex. ImagesPlate 4Plate 1Plate 2Plate 3 PMID:4136579

Artificial vision: needs, functioning, and testing of a retinal electronic prosthesis.

PubMed

Chader, Gerald J; Weiland, James; Humayun, Mark S

2009-01-01

Hundreds of thousands around the world have poor vision or no vision at all due to inherited retinal degenerations (RDs) like retinitis pigmentosa (RP). Similarly, millions suffer from vision loss due to age-related macular degeneration (AMD). In both of these allied diseases, the primary target for pathology is the retinal photoreceptor cells that dysfunction and die. Secondary neurons though are relatively spared. To replace photoreceptor cell function, an electronic prosthetic device can be used such that retinal secondary neurons receive a signal that simulates an external visual image. The composite device has a miniature video camera mounted on the patient's eyeglasses, which captures images and passes them to a microprocessor that converts the data to an electronic signal. This signal, in turn, is transmitted to an array of electrodes placed on the retinal surface, which transmits the patterned signal to the remaining viable secondary neurons. These neurons (ganglion, bipolar cells, etc.) begin processing the signal and pass it down the optic nerve to the brain for final integration into a visual image. Many groups in different countries have different versions of the device, including brain implants and retinal implants, the latter having epiretinal or subretinal placement. The device furthest along in development is an epiretinal implant sponsored by Second Sight Medical Products (SSMP). Their first-generation device had 16 electrodes with human testing in a Phase 1 clinical trial beginning in 2002. The second-generation device has 60+ electrodes and is currently in Phase 2/3 clinical trial. Increased numbers of electrodes are planned for future versions of the device. Testing of the device's efficacy is a challenge since patients admitted into the trial have little or no vision. Thus, methods must be developed that accurately and reproducibly record small improvements in visual function after implantation. Standard tests such as visual acuity, visual field, electroretinography, or even contrast sensitivity may not adequately capture some aspects of improvement that relate to a better quality of life (QOL). Because of this, some tests are now relying more on "real-world functional capacity" that better assesses possible improvement in aspects of everyday living. Thus, a new battery of tests have been suggested that include (1) standard psychophysical testing, (2) performance in tasks that are used in real-life situations such as object discrimination, mobility, etc., and (3) well-crafted questionnaires that assess the patient's own feelings as to the usefulness of the device. In the Phase 1 trial of the SSMP 16-electrode device, six subjects with severe RP were implanted with ongoing, continuing testing since then. First, it was evident that even limited sight restoration is a slow, learning process that takes months for improvement to become evident. However, light perception was restored in all six patients. Moreover, all subjects ultimately saw discrete phosphenes and could perform simple visual spatial and motion tasks. As mentioned above, a Phase 2/3 trial is now ongoing with a 60+ device. A 250+ device is on the drawing board, and one with over 1000 electrodes is being planned. Each has the possibility of significantly improving a patient's vision and QOL, being smaller and safer in design and lasting for the lifetime of the patient. From theoretical modeling, it is estimated that a device with approximately 1000 electrodes could give good functional vision, i.e., face recognition and reading ability. This could be a reality within 5-10 years from now. In summary, no treatments are currently available for severely affected patients with RP and dry AMD. An electrical prosthetic device appears to offer hope in replacing the function of degenerating or dead photoreceptor neurons. Devices with new, sophisticated designs and increasing numbers of electrodes could allow for long-term restoration of functional sight in patients with improvement in object recognition, mobility, independent living, and general QOL.

Synaptic noise is an information bottleneck in the inner retina during dynamic visual stimulation

PubMed Central

Freed, Michael A; Liang, Zhiyin

2014-01-01

In daylight, noise generated by cones determines the fidelity with which visual signals are initially encoded. Subsequent stages of visual processing require synapses from bipolar cells to ganglion cells, but whether these synapses generate a significant amount of noise was unknown. To characterize noise generated by these synapses, we recorded excitatory postsynaptic currents from mammalian retinal ganglion cells and subjected them to a computational noise analysis. The release of transmitter quanta at bipolar cell synapses contributed substantially to the noise variance found in the ganglion cell, causing a significant loss of fidelity from bipolar cell array to postsynaptic ganglion cell. Virtually all the remaining noise variance originated in the presynaptic circuit. Circuit noise had a frequency content similar to noise shared by ganglion cells but a very different frequency content from noise from bipolar cell synapses, indicating that these synapses constitute a source of independent noise not shared by ganglion cells. These findings contribute a picture of daylight retinal circuits where noise from cones and noise generated by synaptic transmission of cone signals significantly limit visual fidelity. PMID:24297850

Design and validation of a foldable and photovoltaic wide-field epiretinal prosthesis.

PubMed

Ferlauto, Laura; Airaghi Leccardi, Marta Jole Ildelfonsa; Chenais, Naïg Aurelia Ludmilla; Gilliéron, Samuel Charles Antoine; Vagni, Paola; Bevilacqua, Michele; Wolfensberger, Thomas J; Sivula, Kevin; Ghezzi, Diego

2018-03-08

Retinal prostheses have been developed to fight blindness in people affected by outer retinal layer dystrophies. To date, few hundred patients have received a retinal implant. Inspired by intraocular lenses, we have designed a foldable and photovoltaic wide-field epiretinal prosthesis (named POLYRETINA) capable of stimulating wireless retinal ganglion cells. Here we show that within a visual angle of 46.3 degrees, POLYRETINA embeds 2215 stimulating pixels, of which 967 are in the central area of 5 mm, it is foldable to allow implantation through a small scleral incision, and it has a hemispherical shape to match the curvature of the eye. We demonstrate that it is not cytotoxic and respects optical and thermal safety standards; accelerated ageing shows a lifetime of at least 2 years. POLYRETINA represents significant progress towards the improvement of both visual acuity and visual field with the same device, a current challenging issue in the field.

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

Functional vision in children with perinatal brain damage.

PubMed

Alimović, Sonja; Jurić, Nikolina; Bošnjak, Vlatka Mejaški

2014-09-01

Many authors have discussed the effects of visual stimulations on visual functions, but there is no research about the effects on using vision in everyday activities (i.e. functional vision). Children with perinatal brain damage can develop cerebral visual impairment with preserved visual functions (e.g. visual acuity, contrast sensitivity) but poor functional vision. Our aim was to discuss the importance of assessing and stimulating functional vision in children with perinatal brain damage. We assessed visual functions (grating visual acuity, contrast sensitivity) and functional vision (the ability of maintaining visual attention and using vision in communication) in 99 children with perinatal brain damage and visual impairment. All children were assessed before and after the visual stimulation program. Our first assessment results showed that children with perinatal brain damage had significantly more problems in functional vision than in basic visual functions. During the visual stimulation program both variables of functional vision and contrast sensitivity improved significantly, while grating acuity improved only in 2.7% of children. We also found that improvement of visual attention significantly correlated to improvement on all other functions describing vision. Therefore, functional vision assessment, especially assessment of visual attention is indispensable in early monitoring of child with perinatal brain damage.

OVEREXPRESSION OF SERUM RESPONSE FACTOR IN ASTROCYTES IMPROVES NEURONAL PLASTICITY IN A MODEL OF EARLY ALCOHOL EXPOSURE

PubMed Central

PAUL, ARCO P.; MEDINA, ALEXANDRE E.

2012-01-01

Neuronal plasticity deficits underlie many of the cognitive problems seen in Fetal Alcohol Spectrum Disorders (FASD). We have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (OD) plasticity. Recently, we showed that this deficit could be reversed by overexpression of serum response factor (SRF) in the primary visual cortex during the period of monocular deprivation (MD). Surprisingly, this restoration was observed throughout the extent of visual cortex and most of the cells transfected by the virus were positive for the astrocytic marker GFAP rather than the neuronal marker NeuN. Here we test whether overexpression of SRF exclusively in astrocytes is sufficient to restore OD plasticity in alcohol-exposed ferrets. To accomplish that, first we exposed cultured astrocytes to Sindbis viruses carrying either a constitutively active form of SRF (SRF+), a dominant negative (SRF−) or control GFP. After 24h, these astrocytes were implanted in the visual cortex of alcohol-exposed animals or saline controls one day before MD. Optical imaging of intrinsic signals showed that alcohol-exposed animals that were implanted with astrocytes expressing SRF, but not SRF− or GFP, showed robust restoration of OD plasticity in all visual cortex. These findings suggest that overexpression of SRF exclusively in astrocytes can improve neuronal plasticity in FASD. PMID:22742904

Visual improvement for bad handwriting based on Monte-Carlo method

NASA Astrophysics Data System (ADS)

Shi, Cao; Xiao, Jianguo; Xu, Canhui; Jia, Wenhua

2014-03-01

A visual improvement algorithm based on Monte Carlo simulation is proposed in this paper, in order to enhance visual effects for bad handwriting. The whole improvement process is to use well designed typeface so as to optimize bad handwriting image. In this process, a series of linear operators for image transformation are defined for transforming typeface image to approach handwriting image. And specific parameters of linear operators are estimated by Monte Carlo method. Visual improvement experiments illustrate that the proposed algorithm can effectively enhance visual effect for handwriting image as well as maintain the original handwriting features, such as tilt, stroke order and drawing direction etc. The proposed visual improvement algorithm, in this paper, has a huge potential to be applied in tablet computer and Mobile Internet, in order to improve user experience on handwriting.

A Computational Study of How Orientation Bias in the Lateral Geniculate Nucleus Can Give Rise to Orientation Selectivity in Primary Visual Cortex

PubMed Central

Kuhlmann, Levin; Vidyasagar, Trichur R.

2011-01-01

Controversy remains about how orientation selectivity emerges in simple cells of the mammalian primary visual cortex. In this paper, we present a computational model of how the orientation-biased responses of cells in lateral geniculate nucleus (LGN) can contribute to the orientation selectivity in simple cells in cats. We propose that simple cells are excited by lateral geniculate fields with an orientation-bias and disynaptically inhibited by unoriented lateral geniculate fields (or biased fields pooled across orientations), both at approximately the same retinotopic co-ordinates. This interaction, combined with recurrent cortical excitation and inhibition, helps to create the sharp orientation tuning seen in simple cell responses. Along with describing orientation selectivity, the model also accounts for the spatial frequency and length–response functions in simple cells, in normal conditions as well as under the influence of the GABAA antagonist, bicuculline. In addition, the model captures the response properties of LGN and simple cells to simultaneous visual stimulation and electrical stimulation of the LGN. We show that the sharp selectivity for stimulus orientation seen in primary visual cortical cells can be achieved without the excitatory convergence of the LGN input cells with receptive fields along a line in visual space, which has been a core assumption in classical models of visual cortex. We have also simulated how the full range of orientations seen in the cortex can emerge from the activity among broadly tuned channels tuned to a limited number of optimum orientations, just as in the classical case of coding for color in trichromatic primates. PMID:22013414

Characterization of an improved donor fluorescent protein for Förster resonance energy transfer microscopy

PubMed Central

Day, Richard N.; Booker, Cynthia F.; Periasamy, Ammasi

2008-01-01

The genetically encoded fluorescent proteins (FP), used in combination with Förster resonance energy transfer (FRET) microscopy, provide the tools necessary for the direct visualization of protein interactions inside living cells. Typically, the Cerulean and Venus variants of the cyan and yellow FPs are used for FRET studies, but there are limitations to their use. Here, Cerulean and the newly developed monomeric Teal FP (mTFP) are compared as FRET donors for Venus using spectral and fluorescence lifetime measurements from living cells. The results demonstrate that when compared to Cerulean, mTFP has increased brightness, optimal excitation using the standard 458-nm laser line, increased photostability, and improved spectral overlap with Venus. In addition, the two-photon excitation and fluorescence lifetime characteristics are determined for mTFP. Together, these measurements indicate that mTFP is an excellent donor fluorophore for FRET studies, and that its use may improve the detection of interactions involving proteins that are difficult to express, or that need to be produced at low levels in cells. PMID:18601527

Uncertainty Footprint: Visualization of Nonuniform Behavior of Iterative Algorithms Applied to 4D Cell Tracking

PubMed Central

Wan, Y.; Hansen, C.

2018-01-01

Research on microscopy data from developing biological samples usually requires tracking individual cells over time. When cells are three-dimensionally and densely packed in a time-dependent scan of volumes, tracking results can become unreliable and uncertain. Not only are cell segmentation results often inaccurate to start with, but it also lacks a simple method to evaluate the tracking outcome. Previous cell tracking methods have been validated against benchmark data from real scans or artificial data, whose ground truth results are established by manual work or simulation. However, the wide variety of real-world data makes an exhaustive validation impossible. Established cell tracking tools often fail on new data, whose issues are also difficult to diagnose with only manual examinations. Therefore, data-independent tracking evaluation methods are desired for an explosion of microscopy data with increasing scale and resolution. In this paper, we propose the uncertainty footprint, an uncertainty quantification and visualization technique that examines nonuniformity at local convergence for an iterative evaluation process on a spatial domain supported by partially overlapping bases. We demonstrate that the patterns revealed by the uncertainty footprint indicate data processing quality in two algorithms from a typical cell tracking workflow – cell identification and association. A detailed analysis of the patterns further allows us to diagnose issues and design methods for improvements. A 4D cell tracking workflow equipped with the uncertainty footprint is capable of self diagnosis and correction for a higher accuracy than previous methods whose evaluation is limited by manual examinations. PMID:29456279

Foldable iris-fixated intraocular lens implantation in children.

PubMed

Ryan, Andrea; Hartnett, Claire; Lanigan, Bernadette; O'Keefe, Michael

2012-09-01

  To describe the results of foldable iris-fixated intraocular lens (IOL) implantation in children.   Children with high bilateral or unilateral myopia who were intolerant of spectacle or contact lens correction were implanted with an iris-fixated foldable IOL and prospectively followed. We measured pre- and postoperative visual acuity, refraction, endothelial cell density (ECD) and National Eye Institute Visual Functioning Questionnaire-25.   Eleven eyes of six children were implanted. Indications were high bilateral myopia in children with comorbid neurobehavioural disorders, high anisometropia and high myopic astigmatism. Mean preoperative spherical equivalent (SE) refraction was -14.6 dioptres (D)±4.2 SD. Mean follow-up was 15 months. Postoperative SE refraction was -2.40 D±2.40 SD. Corrected distance visual acuity (CDVA) improved from mean logMAR 0.84±0.4 SD to postoperative 0.67±0.34 SD (p=0.005). CDVA was reduced because of coexistent ocular disorders and amblyopia. Vision-related quality of life (QOL) measures improved significantly. There were no intraoperative or postoperative serious complications.   Foldable iris-fixated IOL insertion can give a significant improvement in vision and in vision-related QOL in a subset of paediatric patients with special refractive needs who are intolerant to conventional treatment. Long-term follow-up is required for monitoring of ECD. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

Responses to single photons in visual cells of Limulus

PubMed Central

Borsellino, A.; Fuortes, M. G. F.

1968-01-01

1. A system proposed in a previous article as a model of responses of visual cells has been analysed with the purpose of predicting the features of responses to single absorbed photons. 2. As a result of this analysis, the stochastic variability of responses has been expressed as a function of the amplification of the system. 3. The theoretical predictions have been compared to the results obtained by recording electrical responses of visual cells of Limulus to flashes delivering only few photons. 4. Experimental responses to single photons have been tentatively identified and it was shown that the stochastic variability of these responses is similar to that predicted for a model with a multiplication factor of at least twenty-five. 5. These results lead to the conclusion that the processes responsible for visual responses incorporate some form of amplification. This conclusion may prove useful for identifying the physical mechanisms underlying the transducer action of visual cells. PMID:5664231

Visual field impairment captures disease burden in multiple sclerosis.

PubMed

Ortiz-Perez, Santiago; Andorra, Magí; Sanchez-Dalmau, Bernardo; Torres-Torres, Rubén; Calbet, David; Lampert, Erika J; Alba-Arbalat, Salut; Guerrero-Zamora, Ana M; Zubizarreta, Irati; Sola-Valls, Nuria; Llufriu, Sara; Sepúlveda, María; Saiz, Albert; Villoslada, Pablo; Martinez-Lapiscina, Elena H

2016-04-01

Monitoring disease burden is an unmeet need in multiple sclerosis (MS). Identifying patients at high risk of disability progression will be useful for improving clinical-therapeutic decisions in clinical routine. To evaluate the role of visual field testing in non-optic neuritis eyes (non-ON eyes) as a biomarker of disability progression in MS. In 109 patients of the MS-VisualPath cohort, we evaluated the association between visual field abnormalities and global and cognitive disability markers and brain and retinal imaging markers of neuroaxonal injury using linear regression models adjusted for sex, age, disease duration and use of disease-modifying therapies. We evaluated the risk of disability progression associated to have baseline impaired visual field after 3 years of follow-up. Sixty-two percent of patients showed visual field defects in non-ON eyes. Visual field mean deviation was statistically associated with global disability; brain (normalized brain parenchymal, gray matter volume and lesion load) and retinal (peripapillary retinal nerve fiber layer thickness and macular ganglion cell complex thickness) markers of neuroaxonal damage. Patients with impaired visual field had statistically significative greater disability, lower normalized brain parenchymal volume and higher lesion volume than patients with normal visual field testing. MS patients with baseline impaired VF tripled the risk of disability progression during follow-up [OR = 3.35; 95 % CI (1.10-10.19); p = 0.033]. The association of visual field impairment with greater disability and neuroaxonal injury and higher risk of disability progression suggest that VF could be used to monitor MS disease burden.

Methane rescues retinal ganglion cells and limits retinal mitochondrial dysfunction following optic nerve crush.

PubMed

Wang, Ruobing; Sun, Qinglei; Xia, Fangzhou; Chen, Zeli; Wu, Jiangchun; Zhang, Yuelu; Xu, Jiajun; Liu, Lin

2017-06-01

Secondary degeneration is a common event in traumatic central nervous system disorders, which involves neuronal apoptosis and mitochondrial dysfunction. Exogenous methane exerts the therapeutic effects in many organ injury. Our study aims to investigate the potential neuroprotection of methane in a rat model of optic nerve crush (ONC). Adult male Sprague-Dawley rats were subjected to ONC and administrated intraperitoneally with methane-saturated or normal saline (10 ml/kg) once per day for one week after ONC. The retinal ganglion cells (RGCs) density was assessed by hematoxylin and eosin staining and Fluoro-Gold retrogradely labeling. Visual function was evaluated by flash visual evoked potentials (FVEP). The retinal apoptosis was measured by terminal-deoxy-transferase-mediated dUTP nick end labeling (TUNEL) assay and the expression of apoptosis-related factors, such as phosphorylated Bcl-2-associated death promoter (pBAD), phosphorylated glycogen synthase kinase-3β (pGSK-3β), Bcl-2 associated X protein (Bax) and Bcl-2 extra large (Bcl-xL). Retinal mitochondrial function was assessed by the mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), the mitochondrial DNA (mtDNA) copy number, citrate synthase activity and ATP content. Methane treatment significantly improved the RGC loss and visual dysfunction following ONC. As expected, methane also remarkably inhibited the retinal neural apoptosis, such as the fewer TUNEL-positive cells in ganglion cell layer, accompanied by the up-regulations of anti-apoptotic factors (pGSK-3β, pBAD, Bcl-xL) and the down-regulation of pro-apoptotic factor (Bax). Furthermore, methane treatment suppressed up-regulations of critical mitochondrial components (PGC-1α, NRF1 and TFAM) mRNA and mtDNA copy number, as well as improved the reduction of functional mitochondria markers, including citrate synthase activity and ATP content, in retinas with ONC. Taken together, methane treatment promotes RGC survival and limits retinal mitochondrial dysfunction against ONC insult. Methane can be a potential neuroprotective agent for traumatic and glaucomatous neurodegeneration. Copyright © 2017. Published by Elsevier Ltd.

Ultraviolet Light Enhances the Bovine Serum Albumin Fixation for Acid Fast Bacilli Stain

PubMed Central

Lai, Pei-Yin; Lee, Shih-Yi; Chou, Yu-Ching; Fu, Yung-Chieh; Wu, Chen-Cheng; Chiueh, Tzong-Shi

2014-01-01

The use of a liquid culture system such as MGIT broth has greatly improved the sensitivity of isolating mycobacteria in clinical laboratories. Microscopic visualization of acid fast bacilli (AFB) in the culture positive MGIT broth remains the first routine step for rapidly indicating the presence of mycobacteria. We modified an ultraviolet (UV) light fixation process to increase AFB cells adherence to the slide. The retained haze proportion of a 1-cm circle marked area on the smear slide was quantified after the staining procedure indicating the adherence degree of AFB cells. More AFB cells were preserved on the slide after exposure to UV light of either germicidal lamp or UV crosslinker in a time-dependent manner. We demonstrated both the bovine serum albumin (BSA) in MGIT media and UV light exposure were required for enhancing fixation of AFB cells. While applying to AFB stains for 302 AFB positive MGIT broths in clinics, more AFB cells were retained and observed on smear slides prepared by the modified fixation procedure rather than by the conventional method. The modified fixation procedure was thus recommended for improving the sensitivity of microscopic diagnosis of AFB cells in culture positive MGIT broth. PMID:24586725

Commercial Truck Driver Health and Safety: Exploring Distracted Driving Performance and Self-Reported Driving Skill.

PubMed

Stavrinos, Despina; Heaton, Karen; Welburn, Sharon C; McManus, Benjamin; Griffin, Russell; Fine, Philip R

2016-08-01

Reducing distracters detrimental to commercial truck driving is a critical component of improving the safety performance of commercial drivers, and makes the highways safer for all drivers. This study used a driving simulator to examine effects of cell phone, texting, and email distractions as well as self-reported driver optimism bias on the driving performance of commercial truck drivers. Results revealed that more visually demanding tasks were related to poorer driving performance. However, the cell phone task resulted in less off-the-road eye glances. Drivers reporting being "very skilled" displayed poorer driving performance than those reporting being "skilled." Onboard communication devices provide a practical, yet visually and manually demanding, solution for connecting drivers and dispatchers. Trucking company policies should minimize interaction between dispatchers and drivers when the truck is in motion. Training facilities should integrate driving simulators into the instruction of commercial drivers, targeting over-confident drivers. © 2016 The Author(s).

o-Fluorination of aromatic azides yields improved azido-based fluorescent probes for hydrogen sulfide: synthesis, spectra, and bioimaging.

PubMed

Wei, Chao; Wang, Runyu; Wei, Lv; Cheng, Longhuai; Li, Zhifei; Xi, Zhen; Yi, Long

2014-12-01

Hydrogen sulfide (H2S) is an endogenously produced gaseous signaling molecule with multiple biological functions. To visualize the endogenous in situ production of H2S in real time, new coumarin- and boron-dipyrromethene-based fluorescent turn-on probes were developed for fast sensing of H2S in aqueous buffer and in living cells. Introduction of a fluoro group in the ortho position of the aromatic azide can lead to a greater than twofold increase in the rate of reaction with H2S. On the basis of o-fluorinated aromatic azides, fluorescent probes with high sensitivity and selectivity toward H2S over other biologically relevant species were designed and synthesized. The probes can be used to in situ to visualize exogenous H2S and D-cysteine-dependent endogenously produced H2S in living cells, which makes them promising tools for potential applications in H2S biology. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Learning viewpoint invariant object representations using a temporal coherence principle.

PubMed

Einhäuser, Wolfgang; Hipp, Jörg; Eggert, Julian; Körner, Edgar; König, Peter

2005-07-01

Invariant object recognition is arguably one of the major challenges for contemporary machine vision systems. In contrast, the mammalian visual system performs this task virtually effortlessly. How can we exploit our knowledge on the biological system to improve artificial systems? Our understanding of the mammalian early visual system has been augmented by the discovery that general coding principles could explain many aspects of neuronal response properties. How can such schemes be transferred to system level performance? In the present study we train cells on a particular variant of the general principle of temporal coherence, the "stability" objective. These cells are trained on unlabeled real-world images without a teaching signal. We show that after training, the cells form a representation that is largely independent of the viewpoint from which the stimulus is looked at. This finding includes generalization to previously unseen viewpoints. The achieved representation is better suited for view-point invariant object classification than the cells' input patterns. This property to facilitate view-point invariant classification is maintained even if training and classification take place in the presence of an--also unlabeled--distractor object. In summary, here we show that unsupervised learning using a general coding principle facilitates the classification of real-world objects, that are not segmented from the background and undergo complex, non-isomorphic, transformations.

Bilateral Posterior Scleritis Associated with Giant Cell Arteritis: A Case Report.

PubMed

Erdogan, Mehmet; Sayin, Nihat; Yıldız Ekinci, Dilbade; Bayramoglu, Sadik

2017-09-15

To report a case of bilateral posterior scleritis associated with giant cell arteritis Case Report: A 62-year-old female patient presented with bilateral progressive vision loss was diagnosed with bilateral posterior scleritis. According to clinical signs and symptoms and laboratory testing, Giant cell arteritis was also diagnosed. Within 8 weeks of the corticosteroid treatment, the serous retinal detachments completely resolved and choroidal thickness decreased in both eyes. Visual acuity increased, and the symtoms related to Giant cell arteritis improved. Posterior scleritis is an inflammatory disease that may be associated with many autoimmune systemic diseases. GCA should be thought of particularly in patients over the age of 50 with bilateral involvement, and a relevant detailed history should be obtained for early and correct diagnosis and treatment.

Spinning Disk Confocal Imaging of Neutrophil Migration in Zebrafish

PubMed Central

Lam, Pui-ying; Fischer, Robert S; Shin, William D.; Waterman, Clare M; Huttenlocher, Anna

2014-01-01

Live-cell imaging techniques have been substantially improved due to advances in confocal microscopy instrumentation coupled with ultrasensitive detectors. The spinning disk confocal system is capable of generating images of fluorescent live samples with broad dynamic range and high temporal and spatial resolution. The ability to acquire fluorescent images of living cells in vivo on a millisecond timescale allows the dissection of biological processes that have not previously been visualized in a physiologically relevant context. In vivo imaging of rapidly moving cells such as neutrophils can be technically challenging. In this chapter, we describe the practical aspects of imaging neutrophils in zebrafish embryos using spinning disk confocal microscopy. Similar setups can also be applied to image other motile cell types and signaling processes in translucent animals or tissues. PMID:24504955

Change in vision, visual disability, and health after cataract surgery.

PubMed

Helbostad, Jorunn L; Oedegaard, Maria; Lamb, Sarah E; Delbaere, Kim; Lord, Stephen R; Sletvold, Olav

2013-04-01

Cataract surgery improves vision and visual functioning; the effect on general health is not established. We investigated if vision, visual functioning, and general health follow the same trajectory of change the year after cataract surgery and if changes in vision explain changes in visual disability and general health. One-hundred forty-eight persons, with a mean (SD) age of 78.9 (5.0) years (70% bilateral surgery), were assessed before and 6 weeks and 12 months after surgery. Visual disability and general health were assessed by the CatQuest-9SF and the Short Formular-36. Corrected binocular visual acuity, visual field, stereo acuity, and contrast vision improved (P < 0.001) from before to 6 weeks after surgery, with further improvements of visual acuity evident up to 12 months (P = 0.034). Cataract surgery had an effect on visual disability 1 year later (P < 0.001). Physical and mental health improved after surgery (P < 0.01) but had returned to presurgery level after 12 months. Vision changes did not explain visual disability and general health 6 weeks after surgery. Vision improved and visual disability decreased in the year after surgery, whereas changes in general health and visual functioning were short-term effects. Lack of associations between changes in vision and self-reported disability and general health suggests that the degree of vision changes and self-reported health do not have a linear relationship.

Synaptic Mechanisms Generating Orientation Selectivity in the ON Pathway of the Rabbit Retina

PubMed Central

Venkataramani, Sowmya

2016-01-01

Neurons that signal the orientation of edges within the visual field have been widely studied in primary visual cortex. Much less is known about the mechanisms of orientation selectivity that arise earlier in the visual stream. Here we examine the synaptic and morphological properties of a subtype of orientation-selective ganglion cell in the rabbit retina. The receptive field has an excitatory ON center, flanked by excitatory OFF regions, a structure similar to simple cell receptive fields in primary visual cortex. Examination of the light-evoked postsynaptic currents in these ON-type orientation-selective ganglion cells (ON-OSGCs) reveals that synaptic input is mediated almost exclusively through the ON pathway. Orientation selectivity is generated by larger excitation for preferred relative to orthogonal stimuli, and conversely larger inhibition for orthogonal relative to preferred stimuli. Excitatory orientation selectivity arises in part from the morphology of the dendritic arbors. Blocking GABAA receptors reduces orientation selectivity of the inhibitory synaptic inputs and the spiking responses. Negative contrast stimuli in the flanking regions produce orientation-selective excitation in part by disinhibition of a tonic NMDA receptor-mediated input arising from ON bipolar cells. Comparison with earlier studies of OFF-type OSGCs indicates that diverse synaptic circuits have evolved in the retina to detect the orientation of edges in the visual input. SIGNIFICANCE STATEMENT A core goal for visual neuroscientists is to understand how neural circuits at each stage of the visual system extract and encode features from the visual scene. This study documents a novel type of orientation-selective ganglion cell in the retina and shows that the receptive field structure is remarkably similar to that of simple cells in primary visual cortex. However, the data indicate that, unlike in the cortex, orientation selectivity in the retina depends on the activity of inhibitory interneurons. The results further reveal the physiological basis for feature detection in the visual system, elucidate the synaptic mechanisms that generate orientation selectivity at an early stage of visual processing, and illustrate a novel role for NMDA receptors in retinal processing. PMID:26985041

Synaptic Mechanisms Generating Orientation Selectivity in the ON Pathway of the Rabbit Retina.

PubMed

Venkataramani, Sowmya; Taylor, W Rowland

2016-03-16

Neurons that signal the orientation of edges within the visual field have been widely studied in primary visual cortex. Much less is known about the mechanisms of orientation selectivity that arise earlier in the visual stream. Here we examine the synaptic and morphological properties of a subtype of orientation-selective ganglion cell in the rabbit retina. The receptive field has an excitatory ON center, flanked by excitatory OFF regions, a structure similar to simple cell receptive fields in primary visual cortex. Examination of the light-evoked postsynaptic currents in these ON-type orientation-selective ganglion cells (ON-OSGCs) reveals that synaptic input is mediated almost exclusively through the ON pathway. Orientation selectivity is generated by larger excitation for preferred relative to orthogonal stimuli, and conversely larger inhibition for orthogonal relative to preferred stimuli. Excitatory orientation selectivity arises in part from the morphology of the dendritic arbors. Blocking GABAA receptors reduces orientation selectivity of the inhibitory synaptic inputs and the spiking responses. Negative contrast stimuli in the flanking regions produce orientation-selective excitation in part by disinhibition of a tonic NMDA receptor-mediated input arising from ON bipolar cells. Comparison with earlier studies of OFF-type OSGCs indicates that diverse synaptic circuits have evolved in the retina to detect the orientation of edges in the visual input. A core goal for visual neuroscientists is to understand how neural circuits at each stage of the visual system extract and encode features from the visual scene. This study documents a novel type of orientation-selective ganglion cell in the retina and shows that the receptive field structure is remarkably similar to that of simple cells in primary visual cortex. However, the data indicate that, unlike in the cortex, orientation selectivity in the retina depends on the activity of inhibitory interneurons. The results further reveal the physiological basis for feature detection in the visual system, elucidate the synaptic mechanisms that generate orientation selectivity at an early stage of visual processing, and illustrate a novel role for NMDA receptors in retinal processing. Copyright © 2016 the authors 0270-6474/16/363336-14$15.00/0.

Supplementation with macular carotenoids improves visual performance of transgenic mice.

PubMed

Li, Binxing; Rognon, Gregory T; Mattinson, Ty; Vachali, Preejith P; Gorusupudi, Aruna; Chang, Fu-Yen; Ranganathan, Arunkumar; Nelson, Kelly; George, Evan W; Frederick, Jeanne M; Bernstein, Paul S

2018-07-01

Carotenoid supplementation can improve human visual performance, but there is still no validated rodent model to test their effects on visual function in laboratory animals. We recently showed that mice deficient in β-carotene oxygenase 2 (BCO2) and/or β-carotene oxygenase 1 (BCO1) enzymes can accumulate carotenoids in their retinas, allowing us to investigate the effects of carotenoids on the visual performance of mice. Using OptoMotry, a device to measure visual function in rodents, we examined the effect of zeaxanthin, lutein, and β-carotene on visual performance of various BCO knockout mice. We then transgenically expressed the human zeaxanthin-binding protein GSTP1 (hGSTP1) in the rods of bco2 -/- mice to examine if delivering more zeaxanthin to retina will improve their visual function further. The visual performance of bco2 -/- mice fed with zeaxanthin or lutein was significantly improved relative to control mice fed with placebo beadlets. β-Carotene had no significant effect in bco2 -/- mice but modestly improved cone visual function of bco1 -/- mice. Expression of hGSTP1 in the rods of bco2 -/- mice resulted in a 40% increase of retinal zeaxanthin and further improvement of visual performance. This work demonstrates that these "macular pigment mice" may serve as animal models to study carotenoid function in the retina. Copyright © 2018 Elsevier Inc. All rights reserved.

Is improved contrast sensitivity a natural consequence of visual training?

PubMed Central

Levi, Aaron; Shaked, Danielle; Tadin, Duje; Huxlin, Krystel R.

2015-01-01

Many studies have shown that training and testing conditions modulate specificity of visual learning to trained stimuli and tasks. In visually impaired populations, generalizability of visual learning to untrained stimuli/tasks is almost always reported, with contrast sensitivity (CS) featuring prominently among these collaterally-improved functions. To understand factors underlying this difference, we measured CS for direction and orientation discrimination in the visual periphery of three groups of visually-intact subjects. Group 1 trained on an orientation discrimination task with static Gabors whose luminance contrast was decreased as performance improved. Group 2 trained on a global direction discrimination task using high-contrast random dot stimuli previously used to recover motion perception in cortically blind patients. Group 3 underwent no training. Both forms of training improved CS with some degree of specificity for basic attributes of the trained stimulus/task. Group 1's largest enhancement was in CS around the trained spatial/temporal frequencies; similarly, Group 2's largest improvements occurred in CS for discriminating moving and flickering stimuli. Group 3 saw no significant CS changes. These results indicate that CS improvements may be a natural consequence of multiple forms of visual training in visually intact humans, albeit with some specificity to the trained visual domain(s). PMID:26305736

Cartograms Facilitate Communication of Climate Change Risks and Responsibilities

NASA Astrophysics Data System (ADS)

Döll, Petra

2017-12-01

Communication of climate change (CC) risks is challenging, in particular if global-scale spatially resolved quantitative information is to be conveyed. Typically, visualization of CC risks, which arise from the combination of hazard, exposure and vulnerability, is confined to showing only the hazards in the form of global thematic maps. This paper explores the potential of contiguous value-by-area cartograms, that is, distorted density-equalizing maps, for improving communication of CC risks and the countries' differentiated responsibilities for CC. Two global-scale cartogram sets visualize, as an example, groundwater-related CC risks in 0.5° grid cells, another one the correlation of (cumulative) fossil-fuel carbon dioxide emissions with the countries' population and gross domestic product. Viewers of the latter set visually recognize the lack of global equity and that the countries' wealth has been built on harmful emissions. I recommend that CC risks are communicated by bivariate gridded cartograms showing the hazard in color and population, or a combination of population and a vulnerability indicator, by distortion of grid cells. Gridded cartograms are also appropriate for visualizing the availability of natural resources to humans. For communicating complex information, sets of cartograms should be carefully designed instead of presenting single cartograms. Inclusion of a conventionally distorted map enhances the viewers' capability to take up the information represented by distortion. Empirical studies about the capability of global cartograms to convey complex information and to trigger moral emotions should be conducted, with a special focus on risk communication.

Receptive Field Vectors of Genetically-Identified Retinal Ganglion Cells Reveal Cell-Type-Dependent Visual Functions

PubMed Central

Katz, Matthew L.; Viney, Tim J.; Nikolic, Konstantin

2016-01-01

Sensory stimuli are encoded by diverse kinds of neurons but the identities of the recorded neurons that are studied are often unknown. We explored in detail the firing patterns of eight previously defined genetically-identified retinal ganglion cell (RGC) types from a single transgenic mouse line. We first introduce a new technique of deriving receptive field vectors (RFVs) which utilises a modified form of mutual information (“Quadratic Mutual Information”). We analysed the firing patterns of RGCs during presentation of short duration (~10 second) complex visual scenes (natural movies). We probed the high dimensional space formed by the visual input for a much smaller dimensional subspace of RFVs that give the most information about the response of each cell. The new technique is very efficient and fast and the derivation of novel types of RFVs formed by the natural scene visual input was possible even with limited numbers of spikes per cell. This approach enabled us to estimate the 'visual memory' of each cell type and the corresponding receptive field area by calculating Mutual Information as a function of the number of frames and radius. Finally, we made predictions of biologically relevant functions based on the RFVs of each cell type. RGC class analysis was complemented with results for the cells’ response to simple visual input in the form of black and white spot stimulation, and their classification on several key physiological metrics. Thus RFVs lead to predictions of biological roles based on limited data and facilitate analysis of sensory-evoked spiking data from defined cell types. PMID:26845435

Improved Discrimination of Visual Stimuli Following Repetitive Transcranial Magnetic Stimulation

PubMed Central

Waterston, Michael L.; Pack, Christopher C.

2010-01-01

Background Repetitive transcranial magnetic stimulation (rTMS) at certain frequencies increases thresholds for motor-evoked potentials and phosphenes following stimulation of cortex. Consequently rTMS is often assumed to introduce a “virtual lesion” in stimulated brain regions, with correspondingly diminished behavioral performance. Methodology/Principal Findings Here we investigated the effects of rTMS to visual cortex on subjects' ability to perform visual psychophysical tasks. Contrary to expectations of a visual deficit, we find that rTMS often improves the discrimination of visual features. For coarse orientation tasks, discrimination of a static stimulus improved consistently following theta-burst stimulation of the occipital lobe. Using a reaction-time task, we found that these improvements occurred throughout the visual field and lasted beyond one hour post-rTMS. Low-frequency (1 Hz) stimulation yielded similar improvements. In contrast, we did not find consistent effects of rTMS on performance in a fine orientation discrimination task. Conclusions/Significance Overall our results suggest that rTMS generally improves or has no effect on visual acuity, with the nature of the effect depending on the type of stimulation and the task. We interpret our results in the context of an ideal-observer model of visual perception. PMID:20442776

Visualization and Image Analysis of Yeast Cells.

PubMed

Bagley, Steve

2016-01-01

When converting real-life data via visualization to numbers and then onto statistics the whole system needs to be considered so that conversion from the analogue to the digital is accurate and repeatable. Here we describe the points to consider when approaching yeast cell analysis visualization, processing, and analysis of a population by screening techniques.

Clustergrammer, a web-based heatmap visualization and analysis tool for high-dimensional biological data

PubMed Central

Fernandez, Nicolas F.; Gundersen, Gregory W.; Rahman, Adeeb; Grimes, Mark L.; Rikova, Klarisa; Hornbeck, Peter; Ma’ayan, Avi

2017-01-01

Most tools developed to visualize hierarchically clustered heatmaps generate static images. Clustergrammer is a web-based visualization tool with interactive features such as: zooming, panning, filtering, reordering, sharing, performing enrichment analysis, and providing dynamic gene annotations. Clustergrammer can be used to generate shareable interactive visualizations by uploading a data table to a web-site, or by embedding Clustergrammer in Jupyter Notebooks. The Clustergrammer core libraries can also be used as a toolkit by developers to generate visualizations within their own applications. Clustergrammer is demonstrated using gene expression data from the cancer cell line encyclopedia (CCLE), original post-translational modification data collected from lung cancer cells lines by a mass spectrometry approach, and original cytometry by time of flight (CyTOF) single-cell proteomics data from blood. Clustergrammer enables producing interactive web based visualizations for the analysis of diverse biological data. PMID:28994825

Causal evidence for retina dependent and independent visual motion computations in mouse cortex

PubMed Central

Hillier, Daniel; Fiscella, Michele; Drinnenberg, Antonia; Trenholm, Stuart; Rompani, Santiago B.; Raics, Zoltan; Katona, Gergely; Juettner, Josephine; Hierlemann, Andreas; Rozsa, Balazs; Roska, Botond

2017-01-01

How neuronal computations in the sensory periphery contribute to computations in the cortex is not well understood. We examined this question in the context of visual-motion processing in the retina and primary visual cortex (V1) of mice. We disrupted retinal direction selectivity – either exclusively along the horizontal axis using FRMD7 mutants or along all directions by ablating starburst amacrine cells – and monitored neuronal activity in layer 2/3 of V1 during stimulation with visual motion. In control mice, we found an overrepresentation of cortical cells preferring posterior visual motion, the dominant motion direction an animal experiences when it moves forward. In mice with disrupted retinal direction selectivity, the overrepresentation of posterior-motion-preferring cortical cells disappeared, and their response at higher stimulus speeds was reduced. This work reveals the existence of two functionally distinct, sensory-periphery-dependent and -independent computations of visual motion in the cortex. PMID:28530661

Activation of cholecystokinin neurons in the dorsal pallium of the telencephalon is indispensable for the acquisition of chick imprinting behavior.

PubMed

Maekawa, Fumihiko; Nakamori, Tomoharu; Uchimura, Motoaki; Fujiwara, Ken; Yada, Toshihiko; Tsukahara, Shinji; Kanamatsu, Tomoyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

2007-09-01

Chick imprinting behavior is a good model for the study of learning and memory. Imprinting object is recognized and processed in the visual wulst, and the memory is stored in the intermediate medial mesopallium in the dorsal pallium of the telencephalon. We identified chicken cholecystokinin (CCK)-expressing cells localized in these area. The number of CCK mRNA-positive cells increased in chicks underwent imprinting training, and these cells expressed nuclear Fos immunoreactivity at high frequency in these regions. Most of these CCK-positive cells were glutamatergic and negative for parvalbumin immunoreactivity. Semi-quantitative PCR analysis revealed that the CCK mRNA levels were significantly increased in the trained chicks compared with untrained chicks. In contrast, the increase in CCK- and c-Fos-double-positive cells associated with the training was not observed after closure of the critical period. These results indicate that CCK cells in the dorsal pallium are activated acutely by visual training that can elicit imprinting. In addition, the CCK receptor antagonist significantly suppressed the acquisition of memory. These results suggest that the activation of CCK cells in the visual wulst as well as in the intermediate medial mesopallium by visual stimuli is indispensable for the acquisition of visual imprinting.

Single cell integration of animate form, motion and location in the superior temporal cortex of the macaque monkey.

PubMed

Jellema, Tjeerd; Maassen, Gerard; Perrett, David I

2004-07-01

This study investigated the cellular mechanisms in the anterior part of the superior temporal sulcus (STSa) that underlie the integration of different features of the same visually perceived animate object. Three visual features were systematically manipulated: form, motion and location. In 58% of a population of cells selectively responsive to the sight of a walking agent, the location of the agent significantly influenced the cell's response. The influence of position was often evident in intricate two- and three-way interactions with the factors form and/or motion. For only one of the 31 cells tested, the response could be explained by just a single factor. For all other cells at least two factors, and for half of the cells (52%) all three factors, played a significant role in controlling responses. Our findings support a reformulation of the Ungerleider and Mishkin model, which envisages a subdivision of the visual processing into a ventral 'what' and a dorsal 'where' stream. We demonstrated that at least part of the temporal cortex ('what' stream) makes ample use of visual spatial information. Our findings open up the prospect of a much more elaborate integration of visual properties of animate objects at the single cell level. Such integration may support the comprehension of animals and their actions.

Lithium Self-Discharge and Its Prevention: Direct Visualization through In Situ Electrochemical Scanning Transmission Electron Microscopy

DOE PAGES

Harrison, Katharine L.; Zavadil, Kevin R.; Hahn, Nathan T.; ...

2017-11-07

To understand the mechanism that controls low-aspect-ratio lithium deposition morphologies for Li-metal anodes in batteries, we conducted direct visualization of Li-metal deposition and stripping behavior through nanoscale in situ electrochemical scanning transmission electron microscopy (EC-STEM) and macroscale-cell electrochemistry experiments in a recently developed and promising solvate electrolyte, 4 M lithium bis(fluorosulfonyl)imide in 1,2-dimethoxyethane. In contrast to published coin cell studies in the same electrolyte, our experiments revealed low Coulombic efficiencies and inhomogeneous Li morphology during in situ observation. In addition, we conclude that this discrepancy in Coulombic efficiency and morphology of the Li deposits was dependent on the presence ofmore » a compressed lithium separator interface, as we have confirmed through macroscale (not in the transmission electron microscope) electrochemical experiments. Our data suggests that cell compression changed how the solid-electrolyte interphase formed, which is likely responsible for improved morphology and Coulombic efficiency with compression. Furthermore, during the in situ EC-STEM experiments, we observed direct evidence of nanoscale self-discharge in the solvate electrolyte (in the state of electrical isolation). This self-discharge was duplicated in the macroscale, but it was less severe with electrode compression, likely due to a more passivating and corrosion-resistant solid-electrolyte interphase formed in the presence of compression. By combining the solvate electrolyte with a protective LiAl 0.3S coating, we show that the Li nucleation density increased during deposition, leading to improved morphological uniformity. In conclusion, self-discharge was suppressed during rest periods in the cycling profile with coatings present, as evidenced through EC-STEM and confirmed with coin cell data.« less

Lithium Self-Discharge and Its Prevention: Direct Visualization through In Situ Electrochemical Scanning Transmission Electron Microscopy.

PubMed

Harrison, Katharine L; Zavadil, Kevin R; Hahn, Nathan T; Meng, Xiangbo; Elam, Jeffrey W; Leenheer, Andrew; Zhang, Ji-Guang; Jungjohann, Katherine L

2017-11-28

To understand the mechanism that controls low-aspect-ratio lithium deposition morphologies for Li-metal anodes in batteries, we conducted direct visualization of Li-metal deposition and stripping behavior through nanoscale in situ electrochemical scanning transmission electron microscopy (EC-STEM) and macroscale-cell electrochemistry experiments in a recently developed and promising solvate electrolyte, 4 M lithium bis(fluorosulfonyl)imide in 1,2-dimethoxyethane. In contrast to published coin cell studies in the same electrolyte, our experiments revealed low Coulombic efficiencies and inhomogeneous Li morphology during in situ observation. We conclude that this discrepancy in Coulombic efficiency and morphology of the Li deposits was dependent on the presence of a compressed lithium separator interface, as we have confirmed through macroscale (not in the transmission electron microscope) electrochemical experiments. Our data suggests that cell compression changed how the solid-electrolyte interphase formed, which is likely responsible for improved morphology and Coulombic efficiency with compression. Furthermore, during the in situ EC-STEM experiments, we observed direct evidence of nanoscale self-discharge in the solvate electrolyte (in the state of electrical isolation). This self-discharge was duplicated in the macroscale, but it was less severe with electrode compression, likely due to a more passivating and corrosion-resistant solid-electrolyte interphase formed in the presence of compression. By combining the solvate electrolyte with a protective LiAl 0.3 S coating, we show that the Li nucleation density increased during deposition, leading to improved morphological uniformity. Furthermore, self-discharge was suppressed during rest periods in the cycling profile with coatings present, as evidenced through EC-STEM and confirmed with coin cell data.

Lithium Self-Discharge and Its Prevention: Direct Visualization through In Situ Electrochemical Scanning Transmission Electron Microscopy

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

Harrison, Katharine L.; Zavadil, Kevin R.; Hahn, Nathan T.

To understand the mechanism that controls low-aspect-ratio lithium deposition morphologies for Li-metal anodes in batteries, we conducted direct visualization of Li-metal deposition and stripping behavior through nanoscale in situ electrochemical scanning transmission electron microscopy (EC-STEM) and macroscale-cell electrochemistry experiments in a recently developed and promising solvate electrolyte, 4 M lithium bis(fluorosulfonyl)imide in 1,2-dimethoxyethane. In contrast to published coin cell studies in the same electrolyte, our experiments revealed low Coulombic efficiencies and inhomogeneous Li morphology during in situ observation. In addition, we conclude that this discrepancy in Coulombic efficiency and morphology of the Li deposits was dependent on the presence ofmore » a compressed lithium separator interface, as we have confirmed through macroscale (not in the transmission electron microscope) electrochemical experiments. Our data suggests that cell compression changed how the solid-electrolyte interphase formed, which is likely responsible for improved morphology and Coulombic efficiency with compression. Furthermore, during the in situ EC-STEM experiments, we observed direct evidence of nanoscale self-discharge in the solvate electrolyte (in the state of electrical isolation). This self-discharge was duplicated in the macroscale, but it was less severe with electrode compression, likely due to a more passivating and corrosion-resistant solid-electrolyte interphase formed in the presence of compression. By combining the solvate electrolyte with a protective LiAl 0.3S coating, we show that the Li nucleation density increased during deposition, leading to improved morphological uniformity. In conclusion, self-discharge was suppressed during rest periods in the cycling profile with coatings present, as evidenced through EC-STEM and confirmed with coin cell data.« less

Live-Cell Imaging of Auxin and Cytokinin Signaling in Maize Female Gametophytes.

PubMed

Chettoor, Antony M; Evans, Matthew M S

2017-01-01

The plant life cycle is characterized by the alternation of generations between genetically active diploid sporophytes and haploid gametophytes. The gametophytes of flowering plants are sexually dimorphic. While the male gametophyte consists of only three cells (two sperm and a vegetative cell) and is released by the parent sporophyte, the female gametophyte (or embryo sac) is more complex and remains imbedded within diploid sporophyte tissues. In maize, the female gametophyte is embedded in a large ovule surrounded with multiple nucellar cell layers impeding live-cell imaging approaches to study embryo sac functions. Here, we describe a simple protocol to visualize embryo sacs with hormonal fluorescent reporters by increasing accessibility of the female gametophyte. The method described is applicable for visualization of any fluorescent embryo sac reporter. The embryo sacs visualization method developed for maize could be extended to facilitate visualization of embryos sac in other important cereals like wheat, rice, and oats.

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

PERSPECTIVE: Is acuity enough? Other considerations in clinical investigations of visual prostheses

NASA Astrophysics Data System (ADS)

Lepri, Bernard P.

2009-06-01

Visual impairing eye diseases are the major frontier facing ophthalmic research today in light of our rapidly aging population. The visual skills necessary for improving the quality of daily function and life are inextricably linked to these impairing diseases. Both research and reimbursement programs are emphasizing outcome-based results. Is improvement in visual acuity alone enough to improve the function and quality of life of visually impaired persons? This perspective summarizes the types of effectiveness endpoints for clinical investigations of visual prostheses that go beyond visual acuity. The clinical investigation of visual prostheses should include visual function, functional vision and quality of life measures. Specifically, they encompass contrast sensitivity, orientation and mobility, activities of daily living and quality of life assessments. The perspective focuses on the design of clinical trials for visual prostheses and the methods of determining effectiveness above and beyond visual acuity that will yield outcomes that are measured by improved function in the visual world and quality of life. The visually impaired population is the primary consideration in this presentation with particular emphases on retinitis pigmentosa and age-related macular degeneration. Clinical trials for visual prostheses cannot be isolated from the need for medical rehabilitation in order to obtain measurements of effectiveness that produce outcomes/evidence-based success. This approach will facilitate improvement in daily function and quality of life of patients with diseases that cause chronic vision impairment. The views and opinions are those of the author and do not necessarily reflect those of the US Food and Drug Administration, the US Department of Health and Human Services or the Public Health Service.

Macular Ganglion Cell Imaging Study: Covariate Effects on the Spectral Domain Optical Coherence Tomography for Glaucoma Diagnosis.

PubMed

Jeong, Jae Hoon; Choi, Yun Jeong; Park, Ki Ho; Kim, Dong Myung; Jeoung, Jin Wook

2016-01-01

To evaluate the effect of multiple covariates on the diagnostic performance of the Cirrus high-definition optical coherence tomography (HD-OCT) for glaucoma detection. A prospective case-control study was performed and included 173 recently diagnosed glaucoma patients and 63 unaffected individuals from the Macular Ganglion Cell Imaging Study. Regression analysis of receiver operating characteristic were conducted to evaluate the influence of age, spherical equivalent, axial length, optic disc size, and visual field index on the macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) measurements. Disease severity, as measured by visual field index, had a significant effect on the diagnostic performance of all Cirrus HD-OCT parameters. Age, axial length and optic disc size were significantly associated with diagnostic accuracy of average peripapillary RNFL thickness, whereas axial length had a significant effect on the diagnostic accuracy of average GCIPL thickness. Diagnostic performance of the Cirrus HD-OCT may be more accurate in the advanced stages of glaucoma than at earlier stages. A smaller optic disc size was significantly associated with improved the diagnostic ability of average RNFL thickness measurements; however, GCIPL thickness may be less affected by age and optic disc size.

An Unroofing Method to Observe the Cytoskeleton Directly at Molecular Resolution Using Atomic Force Microscopy

PubMed Central

Usukura, Eiji; Narita, Akihiro; Yagi, Akira; Ito, Shuichi; Usukura, Jiro

2016-01-01

An improved unroofing method enabled the cantilever of an atomic force microscope (AFM) to reach directly into a cell to visualize the intracellular cytoskeletal actin filaments, microtubules, clathrin coats, and caveolae in phosphate-buffered saline (PBS) at a higher resolution than conventional electron microscopy. All of the actin filaments clearly exhibited a short periodicity of approximately 5–6 nm, which was derived from globular actins linked to each other to form filaments, as well as a long helical periodicity. The polarity of the actin filaments appeared to be determined by the shape of the periodic striations. Microtubules were identified based on their thickness. Clathrin coats and caveolae were observed on the cytoplasmic surface of cell membranes. The area containing clathrin molecules and their terminal domains was directly visualized. Characteristic ridge structures located at the surface of the caveolae were observed at high resolution, similar to those observed with electron microscopy (EM). Overall, unroofing allowed intracellular AFM imaging in a liquid environment with a level of quality equivalent or superior to that of EM. Thus, AFMs are anticipated to provide cutting-edge findings in cell biology and histology. PMID:27273367

Endogenous Sequential Cortical Activity Evoked by Visual Stimuli

PubMed Central

Miller, Jae-eun Kang; Hamm, Jordan P.; Jackson, Jesse; Yuste, Rafael

2015-01-01

Although the functional properties of individual neurons in primary visual cortex have been studied intensely, little is known about how neuronal groups could encode changing visual stimuli using temporal activity patterns. To explore this, we used in vivo two-photon calcium imaging to record the activity of neuronal populations in primary visual cortex of awake mice in the presence and absence of visual stimulation. Multidimensional analysis of the network activity allowed us to identify neuronal ensembles defined as groups of cells firing in synchrony. These synchronous groups of neurons were themselves activated in sequential temporal patterns, which repeated at much higher proportions than chance and were triggered by specific visual stimuli such as natural visual scenes. Interestingly, sequential patterns were also present in recordings of spontaneous activity without any sensory stimulation and were accompanied by precise firing sequences at the single-cell level. Moreover, intrinsic dynamics could be used to predict the occurrence of future neuronal ensembles. Our data demonstrate that visual stimuli recruit similar sequential patterns to the ones observed spontaneously, consistent with the hypothesis that already existing Hebbian cell assemblies firing in predefined temporal sequences could be the microcircuit substrate that encodes visual percepts changing in time. PMID:26063915

Research on optimal DEM cell size for 3D visualization of loess terraces

NASA Astrophysics Data System (ADS)

Zhao, Weidong; Tang, Guo'an; Ji, Bin; Ma, Lei

2009-10-01

In order to represent the complex artificial terrains like loess terraces in Shanxi Province in northwest China, a new 3D visual method namely Terraces Elevation Incremental Visual Method (TEIVM) is put forth by the authors. 406 elevation points and 14 enclosed constrained lines are sampled according to the TIN-based Sampling Method (TSM) and DEM Elevation Points and Lines Classification (DEPLC). The elevation points and constrained lines are used to construct Constrained Delaunay Triangulated Irregular Networks (CD-TINs) of the loess terraces. In order to visualize the loess terraces well by use of optimal combination of cell size and Elevation Increment Value (EIV), the CD-TINs is converted to Grid-based DEM (G-DEM) by use of different combination of cell size and EIV with linear interpolating method called Bilinear Interpolation Method (BIM). Our case study shows that the new visual method can visualize the loess terraces steps very well when the combination of cell size and EIV is reasonable. The optimal combination is that the cell size is 1 m and the EIV is 6 m. Results of case study also show that the cell size should be at least smaller than half of both the terraces average width and the average vertical offset of terraces steps for representing the planar shapes of the terraces surfaces and steps well, while the EIV also should be larger than 4.6 times of the terraces average height. The TEIVM and results above is of great significance to the highly refined visualization of artificial terrains like loess terraces.

Diamond knife-assisted deep anterior lamellar keratoplasty to manage keratoconus.

PubMed

Vajpayee, Rasik B; Maharana, Prafulla K; Sharma, Namrata; Agarwal, Tushar; Jhanji, Vishal

2014-02-01

To evaluate the outcomes of a new surgical technique, diamond knife-assisted deep anterior lamellar keratoplasty (DALK), and compare its visual and refractive results with big-bubble DALK in cases of keratoconus. Tertiary eyecare hospital. Comparative case series. The visual and surgical outcomes of diamond knife-assisted DALK were compared with those of successful big-bubble DALK. Diamond knife-assisted DALK was performed in 19 eyes and big-bubble DALK, in 11 eyes. All surgeries were completed successfully. No intraoperative or postoperative complications occurred with diamond knife-assisted DALK. Six months after diamond knife-assisted DALK, the mean corrected distance visual acuity (CDVA) improved significantly from 1.87 logMAR ± 0.22 (SD) to 0.23 ± 0.06 logMAR, the mean keratometry improved from 65.99 ± 8.86 diopters (D) to 45.13 ± 1.16 D, and the mean keratometric cylinder improved from 7.99 ± 3.81 D to 2.87 ± 0.59 D (all P=.005). Postoperatively, the mean refractive astigmatism was 2.55 ± 0.49 D and the mean spherical equivalent was -1.97 ± 0.56 D. The mean logMAR CDVA (P = .06), postoperative keratometry (P=.64), refractive cylinder (P=.63), and endothelial cell loss (P=.11) were comparable between diamond knife-assisted DALK and big-bubble DALK. Diamond knife-assisted DALK was effective and predictable as a surgical technique for management of keratoconus cases. This technique has the potential to offer visual and refractive outcomes comparable to those of big-bubble DALK. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Optical Molecular Imaging for Diagnosing Intestinal Diseases

PubMed Central

Kim, Sang-Yeob

2013-01-01

Real-time visualization of the molecular signature of cells can be achieved with advanced targeted imaging techniques using molecular probes and fluorescence endoscopy. This molecular optical imaging in gastrointestinal endoscopy is promising for improving the detection of neoplastic lesions, their characterization for patient stratification, and the assessment of their response to molecular targeted therapy and radiotherapy. In inflammatory bowel disease, this method can be used to detect dysplasia in the presence of background inflammation and to visualize inflammatory molecular targets for assessing disease severity and prognosis. Several preclinical and clinical trials have applied this method in endoscopy; however, this field has just started to evolve. Hence, many problems have yet to be solved to enable the clinical application of this novel method. PMID:24340254

Features and functions of nonlinear spatial integration by retinal ganglion cells.

PubMed

Gollisch, Tim

2013-11-01

Ganglion cells in the vertebrate retina integrate visual information over their receptive fields. They do so by pooling presynaptic excitatory inputs from typically many bipolar cells, which themselves collect inputs from several photoreceptors. In addition, inhibitory interactions mediated by horizontal cells and amacrine cells modulate the structure of the receptive field. In many models, this spatial integration is assumed to occur in a linear fashion. Yet, it has long been known that spatial integration by retinal ganglion cells also incurs nonlinear phenomena. Moreover, several recent examples have shown that nonlinear spatial integration is tightly connected to specific visual functions performed by different types of retinal ganglion cells. This work discusses these advances in understanding the role of nonlinear spatial integration and reviews recent efforts to quantitatively study the nature and mechanisms underlying spatial nonlinearities. These new insights point towards a critical role of nonlinearities within ganglion cell receptive fields for capturing responses of the cells to natural and behaviorally relevant visual stimuli. In the long run, nonlinear phenomena of spatial integration may also prove important for implementing the actual neural code of retinal neurons when designing visual prostheses for the eye. Copyright © 2012 Elsevier Ltd. All rights reserved.

Topographic specializations of catecholaminergic cells and ganglion cells and distribution of calcium binding proteins in the crepuscular rock cavy (Kerodon rupestris) retina.

PubMed

Oliveira, Francisco Gilberto; Nascimento-Júnior, Expedito Silva do; Cavalcante, Judney Cley; Guzen, Fausto Pierdoná; Cavalcante, Jeferson de Souza; Soares, Joacil Germano; Cavalcanti, José Rodolfo Lopes de Paiva; Freitas, Leandro Moura de; Costa, Miriam Stela Maris de Oliveira; Andrade-da-Costa, Belmira Lara da Silveira

2018-07-01

The rock cavy (Kerodon rupestris) is a crepuscular Hystricomorpha rodent that has been used in comparative analysis of retinal targets, but its retinal organization remains to be investigated. In order to better characterize its visual system, the present study analyzed neurochemical features related to the topographic organization of catecholaminergic cells and ganglion cells, as well the distribution of calcium-binding proteins in the outer and inner retina. Retinal sections and/or wholemounts were processed using tyrosine hydroxylase (TH), GABA, calbindin, parvalbumin and calretinin immunohistochemistry or Nissl staining. Two types of TH-immunoreactive (TH-IR) cells were found which differ in soma size, dendritic arborization, intensity of TH immunoreactivity and stratification pattern in the inner plexiform layer. The topographic distribution of all TH-IR cells defines a visual streak along the horizontal meridian in the superior retina. The ganglion cells are also distributed in a visual streak and the visual acuity estimated considering their peak density is 4.13 cycles/degree. A subset of TH-IR cells express GABA or calbindin. Calretinin is abundant in most of retinal layers and coexists with calbindin in horizontal cells. Parvalbumin is less abundant and expressed by presumed amacrine cells in the INL and some ganglion cells in the GCL. The topographic distribution of TH-IR cells and ganglion cells in the rock cavy retina indicate a suitable adaptation for using a broad extension of its inferior visual field in aspects that involve resolution, adjustment to ambient light intensity and movement detection without specialized eye movements. Copyright © 2017 Elsevier B.V. All rights reserved.

Retinal specializations and visual ecology in an animal with an extremely elaborate pupil shape: The Little skate Leucoraja (Raja) erinacea Mitchell, 1825.

PubMed

Jinson, S Terrell; Liebich, Jan; Senft, Stephen L; Mäthger, Lydia M

2018-05-14

Investigating retinal specializations offers insights into eye functionality. Using retinal wholemount techniques, we investigated the distribution of retinal ganglion cells in the Little skate Leucoraja erinacea by (1) dye-backfilling into the optic nerve prior to retinal wholemounting; (2) Nissl-staining of retinal wholemounts. Retinas were examined for regional specializations (higher numbers) of ganglion cells that would indicate higher visual acuity in those areas. Total ganglion cell number were low compared to other elasmobranchs (backfilled: average 49,713 total ganglion cells, average peak cell density 1,315 ganglion cells mm -2 ; Nissl-stained: average 47,791 total ganglion cells, average peak cell density 1,319 ganglion cells mm -2 ). Ganglion cells fit into three size categories: small (5-20µm); medium (20-30µm); large: (≥ 30µm), and they were not homogeneously distributed across the retina. There was a dorsally located horizontal visual streak with increased ganglion cell density; additionally, there were approximately 3 local maxima in ganglion cell distribution (potential areae centrales) within this streak in which densities were highest. Using computerized tomography (CT) and micro-CT, geometrical dimensions of the eye were obtained. Combined with ganglion cell distributions, spatial resolving power was determined to be between 1.21 to 1.37 cycles per degree. Additionally, photoreceptor sizes across different retinal areas varied; photoreceptors were longest within the horizontal visual streak. Variations in the locations of retinal specializations appear to be related to the animal's anatomy: shape of the head and eyes, position of eyes, location of tapetum, and shape of pupil, as well as the visual demands associated with lifestyle and habitat type. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Visuomotor properties of corticotectal cells in area 17 and posteromedial lateral suprasylvian (PMLS) cortex of the cat.

PubMed

Weyand, T G; Gafka, A C

2001-01-01

We studied the visuomotor activity of corticotectal (CT) cells in two visual cortical areas [area 17 and the posteromedial lateral suprasylvian cortex (PMLS)] of the cat. The cats were trained in simple oculomotor tasks, and head position was fixed. Most CT cells in both cortical areas gave a vigorous discharge to a small stimulus used to control gaze when it fell within the retinotopically defined visual field. However, the vigor of the visual response did not predict latency to initiate a saccade, saccade velocity, amplitude, or even if a saccade would be made, minimizing any potential role these cells might have in premotor or attentional processes. Most CT cells in both areas were selective for direction of stimulus motion, and cells in PMLS showed a direction preference favoring motion away from points of central gaze. CT cells did not discharge with eye movements in the dark. During eye movements in the light, many CT cells in area 17 increased their activity. In contrast, cells in PMLS, including CT cells, were generally unresponsive during saccades. Paradoxically, cells in PMLS responded vigorously to stimuli moving at saccadic velocities, indicating that the oculomotor system suppresses visual activity elicited by moving the retina across an illuminated scene. Nearly all CT cells showed oscillatory activity in the frequency range of 20-90 Hz, especially in response to visual stimuli. However, this activity was capricious; strong oscillations in one trial could disappear in the next despite identical stimulus conditions. Although the CT cells in both of these regions share many characteristics, the direction anisotropy and the suppression of activity during eye movements which characterize the neurons in PMLS suggests that these two areas have different roles in facilitating perceptual/motor processes at the level of the superior colliculus.

Structural organization of parallel information processing within the tectofugal visual system of the pigeon.

PubMed

Hellmann, B; Güntürkün, O

2001-01-01

Visual information processing within the ascending tectofugal pathway to the forebrain undergoes essential rearrangements between the mesencephalic tectum opticum and the diencephalic nucleus rotundus of birds. The outer tectal layers constitute a two-dimensional map of the visual surrounding, whereas nucleus rotundus is characterized by functional domains in which different visual features such as movement, color, or luminance are processed in parallel. Morphologic correlates of this reorganization were investigated by means of focal injections of the neuronal tracer choleratoxin subunit B into different regions of the nuclei rotundus and triangularis of the pigeon. Dependent on the thalamic injection site, variations in the retrograde labeling pattern of ascending tectal efferents were observed. All rotundal projecting neurons were located within the deep tectal layer 13. Five different cell populations were distinguished that could be differentiated according to their dendritic ramifications within different retinorecipient laminae and their axons projecting to different subcomponents of the nucleus rotundus. Because retinorecipient tectal layers differ in their input from distinct classes of retinal ganglion cells, each tectorotundal cell type probably processes different aspects of the visual surrounding. Therefore, the differential input/output connections of the five tectorotundal cell groups might constitute the structural basis for spatially segregated parallel information processing of different stimulus aspects within the tectofugal visual system. Because two of five rotundal projecting cell groups additionally exhibited quantitative shifts along the dorsoventral extension of the tectum, data also indicate visual field-dependent alterations in information processing for particular visual features. Copyright 2001 Wiley-Liss, Inc.

Real Time Visualization and Manipulation of the Metastatic Trajectory ofBreast Cancer Cell

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-13-1-0173 TITLE: Real-Time Visualization and Manipulation of the Metastatic Trajectory of Breast Cancer Cells ...of this work was to engineer breast cancer cells to irreversibly alter the genome of nearby cells through exosomal transfer of Cre recombinase from...the cancer cells to surrounding cells . Our goal was to use this study to activate green fluorescent protein in the host reporter cells in the

A system and methodology for high-content visual screening of individual intact living cells in suspension

NASA Astrophysics Data System (ADS)

Renaud, Olivier; Heintzmann, Rainer; Sáez-Cirión, Asier; Schnelle, Thomas; Mueller, Torsten; Shorte, Spencer

2007-02-01

Three dimensional imaging provides high-content information from living intact biology, and can serve as a visual screening cue. In the case of single cell imaging the current state of the art uses so-called "axial through-stacking". However, three-dimensional axial through-stacking requires that the object (i.e. a living cell) be adherently stabilized on an optically transparent surface, usually glass; evidently precluding use of cells in suspension. Aiming to overcome this limitation we present here the utility of dielectric field trapping of single cells in three-dimensional electrode cages. Our approach allows gentle and precise spatial orientation and vectored rotation of living, non-adherent cells in fluid suspension. Using various modes of widefield, and confocal microscope imaging we show how so-called "microrotation" can provide a unique and powerful method for multiple point-of-view (three-dimensional) interrogation of intact living biological micro-objects (e.g. single-cells, cell aggregates, and embryos). Further, we show how visual screening by micro-rotation imaging can be combined with micro-fluidic sorting, allowing selection of rare phenotype targets from small populations of cells in suspension, and subsequent one-step single cell cloning (with high-viability). Our methodology combining high-content 3D visual screening with one-step single cell cloning, will impact diverse paradigms, for example cytological and cytogenetic analysis on haematopoietic stem cells, blood cells including lymphocytes, and cancer cells.

Visualizing morphogenesis in transgenic zebrafish embryos using BODIPY TR methyl ester dye as a vital counterstain for GFP.

PubMed

Cooper, Mark S; Szeto, Daniel P; Sommers-Herivel, Greg; Topczewski, Jacek; Solnica-Krezel, Lila; Kang, Hee-Chol; Johnson, Iain; Kimelman, David

2005-02-01

Green fluorescent protein (GFP) technology is rapidly advancing the study of morphogenesis, by allowing researchers to specifically focus on a subset of labeled cells within the living embryo. However, when imaging GFP-labeled cells using confocal microscopy, it is often essential to simultaneously visualize all of the cells in the embryo using dual-channel fluorescence to provide an embryological context for the cells expressing GFP. Although various counterstains are available, part of their fluorescence overlaps with the GFP emission spectra, making it difficult to clearly identify the cells expressing GFP. In this study, we report that a new fluorophore, BODIPY TR methyl ester dye, serves as a versatile vital counterstain for visualizing the cellular dynamics of morphogenesis within living GFP transgenic zebrafish embryos. The fluorescence of this photostable synthetic dye is spectrally separate from GFP fluorescence, allowing dual-channel, three-dimensional (3D) and four-dimensional (4D) confocal image data sets of living specimens to be easily acquired. These image data sets can be rendered subsequently into uniquely informative 3D and 4D visualizations using computer-assisted visualization software. We discuss a variety of immediate and potential applications of BODIPY TR methyl ester dye as a vital visualization counterstain for GFP in transgenic zebrafish embryos. Copyright 2004 Wiley-Liss, Inc.

Emerging category representation in the visual forebrain hierarchy of pigeons (Columba livia).

PubMed

Azizi, Amir Hossein; Pusch, Roland; Koenen, Charlotte; Klatt, Sebastian; Bröcker, Franziska; Thiele, Samuel; Kellermann, Janosch; Güntürkün, Onur; Cheng, Sen

2018-06-06

Recognizing and categorizing visual stimuli are cognitive functions vital for survival, and an important feature of visual systems in primates as well as in birds. Visual stimuli are processed along the ventral visual pathway. At every stage in the hierarchy, neurons respond selectively to more complex features, transforming the population representation of the stimuli. It is therefore easier to read-out category information in higher visual areas. While explicit category representations have been observed in the primate brain, less is known on equivalent processes in the avian brain. Even though their brain anatomies are radically different, it has been hypothesized that visual object representations are comparable across mammals and birds. In the present study, we investigated category representations in the pigeon visual forebrain using recordings from single cells responding to photographs of real-world objects. Using a linear classifier, we found that the population activity in the visual associative area mesopallium ventrolaterale (MVL) distinguishes between animate and inanimate objects, although this distinction is not required by the task. By contrast, a population of cells in the entopallium, a region that is lower in the hierarchy of visual areas and that is related to the primate extrastriate cortex, lacked this information. A model that pools responses of simple cells, which function as edge detectors, can account for the animate vs. inanimate categorization in the MVL, but performance in the model is based on different features than in MVL. Therefore, processing in MVL cells is very likely more abstract than simple computations on the output of edge detectors. Copyright © 2018. Published by Elsevier B.V.

Multi-characteristic opsin enabled vision restoration

NASA Astrophysics Data System (ADS)

Wright, Weldon; Pradhan, Sanjay; Bhattacharya, Sulgana; Mahapatra, Vasu; Tripathy, Ashutosh; Gajjeraman, Sivakumar; Mohanty, Samarendra

2017-02-01

Photodegenerative retinal diseases such as retinitis pigmentosa (RP) and dry age related macular degeneration (dry- AMD) lead to loss of vision in millions of individuals. Currently, no surgical or medical treatment is available though optogenetic therapies are in clinical development. Here, we demonstrate vision restoration using Multi- Characteristics Opsin (MCO1) in animal models with photo-degenerated retina. MCO1 is reliably delivered to specific retinal cells via intravitreal injection of Adeno-Associated Virus, leading to significant improvement in visually guided behavior conducted using a radial-arm water maze. The time to reach platform significantly reduced after delivery of MCO1. Notably, the improvement in visually guided behavior was observed even at light intensity levels orders of magnitude lower than that required for Channelrhodopsin-2 opsin. Chronic light exposure study showed that chronic light exposure did not compromise viability of vMCO1-treated retina. Safe virus-mediated MCO1-delivery has potential for effective gene therapy of diverse retinal degenerations in patients.

Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model

NASA Astrophysics Data System (ADS)

Georges, Joseph F.; Liu, Xiaowei; Eschbacher, Jennifer; Nichols, Joshua; Mooney, Michael A.; Joy, Anna; Spetzler, Robert F.; Feuerstein, Burt G.; Anderson, Trent; Preul, Mark C.; Yan, Hao; Nakaji, Peter

2018-02-01

Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 10 minutes of incubation. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

Method for evaluation of human induced pluripotent stem cell quality using image analysis based on the biological morphology of cells.

PubMed

Wakui, Takashi; Matsumoto, Tsuyoshi; Matsubara, Kenta; Kawasaki, Tomoyuki; Yamaguchi, Hiroshi; Akutsu, Hidenori

2017-10-01

We propose an image analysis method for quality evaluation of human pluripotent stem cells based on biologically interpretable features. It is important to maintain the undifferentiated state of induced pluripotent stem cells (iPSCs) while culturing the cells during propagation. Cell culture experts visually select good quality cells exhibiting the morphological features characteristic of undifferentiated cells. Experts have empirically determined that these features comprise prominent and abundant nucleoli, less intercellular spacing, and fewer differentiating cellular nuclei. We quantified these features based on experts' visual inspection of phase contrast images of iPSCs and found that these features are effective for evaluating iPSC quality. We then developed an iPSC quality evaluation method using an image analysis technique. The method allowed accurate classification, equivalent to visual inspection by experts, of three iPSC cell lines.

Semi-automated discrimination of retinal pigmented epithelial cells in two-photon fluorescence images of mouse retinas.

PubMed

Alexander, Nathan S; Palczewska, Grazyna; Palczewski, Krzysztof

2015-08-01

Automated image segmentation is a critical step toward achieving a quantitative evaluation of disease states with imaging techniques. Two-photon fluorescence microscopy (TPM) has been employed to visualize the retinal pigmented epithelium (RPE) and provide images indicating the health of the retina. However, segmentation of RPE cells within TPM images is difficult due to small differences in fluorescence intensity between cell borders and cell bodies. Here we present a semi-automated method for segmenting RPE cells that relies upon multiple weak features that differentiate cell borders from the remaining image. These features were scored by a search optimization procedure that built up the cell border in segments around a nucleus of interest. With six images used as a test, our method correctly identified cell borders for 69% of nuclei on average. Performance was strongly dependent upon increasing retinosome content in the RPE. TPM image analysis has the potential of providing improved early quantitative assessments of diseases affecting the RPE.

Improving the performance of the amblyopic visual system

PubMed Central

Levi, Dennis M.; Li, Roger W.

2008-01-01

Experience-dependent plasticity is closely linked with the development of sensory function; however, there is also growing evidence for plasticity in the adult visual system. This review re-examines the notion of a sensitive period for the treatment of amblyopia in the light of recent experimental and clinical evidence for neural plasticity. One recently proposed method for improving the effectiveness and efficiency of treatment that has received considerable attention is ‘perceptual learning’. Specifically, both children and adults with amblyopia can improve their perceptual performance through extensive practice on a challenging visual task. The results suggest that perceptual learning may be effective in improving a range of visual performance and, importantly, the improvements may transfer to visual acuity. Recent studies have sought to explore the limits and time course of perceptual learning as an adjunct to occlusion and to investigate the neural mechanisms underlying the visual improvement. These findings, along with the results of new clinical trials, suggest that it might be time to reconsider our notions about neural plasticity in amblyopia. PMID:19008199

A Visual Programming Methodology for Tactical Aircrew Scheduling and Other Applications

DTIC Science & Technology

1991-12-01

prgramming methodology and environment of a user-specific application remains with and is delivered as part of the application, then there is another factor...animation is useful, not only for scheduling applications, but as a general prgramming methodology. Of course, there are a number of improvements...possible using Excel because there is nothing to prevent access to cells. However, it is easy to imagine a spreadsheet which can support the

Optical cylinder designs to increase the field of vision in the osteo-odonto-keratoprosthesis.

PubMed

Hull, C C; Liu, C S; Sciscio, A; Eleftheriadis, H; Herold, J

2000-12-01

The single optical cylinders used in the osteo-odonto-keratoprosthesis (OOKP) are known to produce very small visual fields. Values of 40 degrees are typically quoted. The purpose of this paper is to present designs for new optical cylinders that significantly increase the field of view and therefore improve the visual rehabilitation of patients having an OOKP. Computer ray-tracing techniques were used to design and analyse improved one- and two-piece optical cylinders made from polymethyl methacrylate. All designs were required to have a potential visual acuity of 6/6 before consideration was given to the visual field and optimising off-axis image quality. Aspheric surfaces were used where this significantly improved off-axis image quality. Single optical cylinders, with increased posterior cylinder (intraocular) diameters, gave an increase in the theoretical visual field of 18% (from 76 degrees to 90 degrees) over current designs. Two-piece designs based on an inverted telephoto principle gave theoretical field angles over 120 degrees. Aspheric surfaces were shown to improve the off-axis image quality while maintaining a potential visual acuity of at least 6/6. This may well increase the measured visual field by improving the retinal illuminance off-axis. Results demonstrate that it is possible to significantly increase the theoretical maximum visual field through OOKP optical cylinders. Such designs will improve the visual rehabilitation of patients undergoing this procedure.

Effects of subtenon-injected autologous platelet-rich plasma on visual functions in eyes with retinitis pigmentosa: preliminary clinical results.

PubMed

Arslan, Umut; Özmert, Emin; Demirel, Sibel; Örnek, Firdevs; Şermet, Figen

2018-05-01

One of the main reasons for apoptosis and dormant cell phases in degenerative retinal diseases such as retinitis pigmentosa (RP) is growth factor withdrawal in the cellular microenvironment. Growth factors and neurotrophins can significantly slow down retinal degeneration and cell death in animal models. One possible source of autologous growth factors is platelet-rich plasma. The purpose of this study was to determine if subtenon injections of autologous platelet-rich plasma (aPRP) can have beneficial effects on visual function in RP patients by reactivating dormant photoreceptors. This prospective open-label clinical trial, conducted between September 2016 and February 2017, involved 71 eyes belonging to 48 RP patients with various degrees of narrowed visual field. Forty-nine eyes belonging to 37 patients were injected with aPRP. A comparison group was made up of 11 patients who had symmetrical bilateral narrowed visual field (VF) of both eyes. Among these 11 patients, one eye was injected with aPRP, while the other eye was injected with autologous platelet-poor plasma (aPPP) to serve as a control. The total duration of the study was 9 weeks: the aPRP or aPPP subtenon injections were applied three times, with 3-week intervals between injections, and the patients were followed for three more weeks after the third injection. Visual acuity (VA) tests were conducted on all patients, and VF, microperimetry (MP), and multifocal electroretinography (mfERG) tests were conducted on suitable patients to evaluate the visual function changes before and after the aPRP or aPPP injections. The best-corrected visual acuity values in the ETDRS chart improved by 11.6 letters (from 70 to 81.6 letters) in 19 of 48 eyes following aPRP application; this result, however, was not statistically significant (p = 0.056). Following aPRP injections in 48 eyes, the mean deviation of the VF values improved from - 25.3 to - 23.1 dB (p = 0.0001). Results regarding the mfERG P1 amplitudes improved in ring 1 from 24.4 to 38.5 nv/deg 2 (p = 0.0001), in ring 2 from 6.7 to 9.3 nv/deg 2 (p = 0.0301), and in ring 3 from 3.5 to 4.5 nv/deg 2 (p = 0.0329). The mfERG P1 implicit times improved in ring 1 from 40.0 to 34.4 ms (p = 0.01), in ring 2 from 42.5 to 33.2 ms (p = 0.01), and in ring 3 from 42.1 to 37.9 ms (p = 0.04). The mfERG N1 amplitudes improved in ring 1 from 0.18 to 0.25 nv/deg 2 (p = 0.011) and in ring 2 from 0.05 to 0.08 nv/deg 2 (p = 0.014). The mfERG N1 implicit time also improved in ring 1 from 18.9 to 16.2 ms (p = 0.040) and in ring 2 from 20.9 to 15.5 ms (p = 0.002). No improvement was seen in the 11 control eyes into which aPPP was injected. In the 23 RP patients with macular involvement, the MP average threshold values improved with aPRP injections from 15.0 to 16.4 dB (p = 0.0001). No ocular or systemic adverse events related to the injections or aPRP were observed during the follow-up period. Preliminary clinical results are encouraging in terms of statistically significant improvements in VF, mfERG values, and MP. The subtenon injection of aPRP seems to be a therapeutic option for treatment and might lead to positive results in the vision of RP patients. Long-term results regarding adverse events are unknown. There have not been any serious adverse events and any ophthalmic or systemic side effects for 1 year follow-up. Further studies with long-term follow-up are needed to determine the duration of efficacy and the frequency of application.

Development of Selective Lamellar Keratoplasty within an Asian Corneal Transplant Program: The Singapore Corneal Transplant Study (An American Ophthalmological Society Thesis)

PubMed Central

Tan, Donald; Ang, Marcus; Arundhati, Anshu; Khor, Wei-Boon

2015-01-01

Purpose: To evaluate outcomes of anterior lamellar keratoplasty (ALK) and endothelial keratoplasty (EK) within the Singapore Corneal Transplant Study (SCTS), with the hypothesis that both ALK and EK are able to provide equivalent or improved clinical outcomes, compared to penetrating keratoplasty (PK), and to determine changing trends globally with other international databases. Methods: Clinical data on all transplants performed was derived from our SCTS database, a prospective national keratoplasty registry, and clinical outcomes (graft survival, endothelial cell loss, complications, visual acuity) were compared between PK, ALK, and EK. Global trends on indications and forms of keratoplasty performed in 2011/2012 were obtained from national keratoplasty or eye banking registries, corneal/ophthalmological societies, national eye banks, and national ophthalmic institutions. Results: Global rates of EK surgery vary widely, from 52% (Sweden) to 0% (South Africa), with higher adoption by industrialized countries. ALK adoption rates similarly vary from 28.7% (China) to 1.0% (Philippines). SCTS data show high adoption rates in Singapore: EK 44% and ALK 28%. Our surgical modifications to big-bubble deep anterior lamellar keratoplasty (DALK) surgery resulted in visual outcomes matching PK, and a low conversion to PK of 2.1%, whereas our evolving approaches to donor insertion in Descemet’s stripping automated endothelial keratoplasty (DSAEK) show significant reduction in 1-year postoperative endothelial cell loss rates from 60% (folding), to 22% to 30% (Sheets Glide), to 15% (EndoGlide inserter). Conclusion: Improvements in various forms of ALK and EK surgery can lead to better visual outcomes, longer graft survival, and reduced complications, as compared to PK. Global trends suggest adoption of these procedures at different rates. PMID:26755854

Estimation of ovular fiber production in cotton

DOEpatents

Van't Hof, Jack

1998-09-01

The present invention is a method for rendering cotton fiber cells that are post-anthesis and pre-harvest available for analysis of their physical properties. The method includes the steps of hydrolyzing cotton fiber cells and separating cotton fiber cells from cotton ovules thereby rendering the cells available for analysis. The analysis of the fiber cells is through any suitable means, e.g., visual inspection. Visual inspection of the cells can be accomplished by placing the cells under an instrument for detection, such as microscope or other means.

Quantification of transendothelial migration using three-dimensional confocal microscopy.

PubMed

Cain, Robert J; d'Água, Bárbara Borda; Ridley, Anne J

2011-01-01

Migration of cells across endothelial barriers, termed transendothelial migration (TEM), is an important cellular process that underpins the pathology of many disease states including chronic inflammation and cancer metastasis. While this process can be modeled in vitro using cultured cells, many model systems are unable to provide detailed visual information of cell morphologies and distribution of proteins such as junctional markers, as well as quantitative data on the rate of TEM. Improvements in imaging techniques have made microscopy-based assays an invaluable tool for studying this type of detailed cell movement in physiological processes. In this chapter, we describe a confocal microscopy-based method that can be used to assess TEM of both leukocytes and cancer cells across endothelial barriers in response to a chemotactic gradient, as well as providing information on their migration into a subendothelial extracellular matrix, designed to mimic that found in vivo.

Mixing of Chromatic and Luminance Retinal Signals in Primate Area V1

PubMed Central

Li, Xiaobing; Chen, Yao; Lashgari, Reza; Bereshpolova, Yulia; Swadlow, Harvey A.; Lee, Barry B.; Alonso, Jose Manuel

2015-01-01

Vision emerges from activation of chromatic and achromatic retinal channels whose interaction in visual cortex is still poorly understood. To investigate this interaction, we recorded neuronal activity from retinal ganglion cells and V1 cortical cells in macaques and measured their visual responses to grating stimuli that had either luminance contrast (luminance grating), chromatic contrast (chromatic grating), or a combination of the two (compound grating). As with parvocellular or koniocellular retinal ganglion cells, some V1 cells responded mostly to the chromatic contrast of the compound grating. As with magnocellular retinal ganglion cells, other V1 cells responded mostly to the luminance contrast and generated a frequency-doubled response to equiluminant chromatic gratings. Unlike magnocellular and parvocellular retinal ganglion cells, V1 cells formed a unimodal distribution for luminance/color preference with a 2- to 4-fold bias toward luminance. V1 cells associated with positive local field potentials in deep layers showed the strongest combined responses to color and luminance and, as a population, V1 cells encoded a diverse combination of luminance/color edges that matched edge distributions of natural scenes. Taken together, these results suggest that the primary visual cortex combines magnocellular and parvocellular retinal inputs to increase cortical receptive field diversity and to optimize visual processing of our natural environment. PMID:24464943

Development of practical red fluorescent probe for cytoplasmic calcium ions with greatly improved cell-membrane permeability.

PubMed

Hirabayashi, Kazuhisa; Hanaoka, Kenjiro; Egawa, Takahiro; Kobayashi, Chiaki; Takahashi, Shodai; Komatsu, Toru; Ueno, Tasuku; Terai, Takuya; Ikegaya, Yuji; Nagano, Tetsuo; Urano, Yasuteru

2016-10-01

Fluorescence imaging of calcium ions (Ca(2+)) has become an essential technique for investigation of signaling pathways involving Ca(2+) as a second messenger. But, Ca(2+) signaling is involved in many biological phenomena, and therefore simultaneous visualization of Ca(2+) and other biomolecules (multicolor imaging) would be particularly informative. For this purpose, we set out to develop a fluorescent probe for Ca(2+) that would operate in a different color region (red) from that of probes for other molecules, many of which show green fluorescence, as exemplified by green fluorescent protein (GFP). We previously developed a red fluorescent probe for monitoring cytoplasmic Ca(2+) concentration, based on our established red fluorophore, TokyoMagenta (TM), but there remained room for improvement, especially as regards efficiency of introduction into cells. We considered that this issue was probably mainly due to limited water solubility of the probe. So, we designed and synthesized a red-fluorescent probe with improved water solubility. We confirmed that this Ca(2+) red-fluorescent probe showed high cell-membrane permeability with bright fluorescence. It was successfully applied to fluorescence imaging of not only live cells, but also brain slices, and should be practically useful for multicolor imaging studies of biological mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Numerical and experimental evaluation of microfluidic sorting devices.

PubMed

Taylor, Jay K; Ren, Carolyn L; Stubley, G D

2008-01-01

The development of lab-on-a-chip devices calls for the isolation or separation of specific bioparticles or cells. The design of a miniaturized cell-sorting device for handheld operation must follow the strict parameters associated with lab-on-a-chip technology. The limitations include applied voltage, high efficiency of cell-separation, reliability, size, flow control, and cost, among others. Currently used designs have achieved successful levels of cell isolation; however, further improvements in the microfluidic chip design are important to incorporate into larger systems. This study evaluates specific design modifications that contribute to the reduction of required applied potential aiming for developing portable devices, improved operation reliability by minimizing induced pressure disturbance when electrokinetic pumping is employed, and improved flow control by incorporating directing streams achieving dynamic sorting and counting. The chip designs fabricated in glass and polymeric materials include asymmetric channel widths for sample focusing, nonuniform channel depth for minimizing induced pressure disturbance, directing streams to assist particle flow control, and online filters for reducing channel blockage. Fluorescence-based visualization experimental results of electrokinetic focusing, flow field phenomena, and dynamic sorting demonstrate the advantages of the chip design. Numerical simulations in COMSOL are validated by the experimental data and used to investigate the effects of channel geometry and fluid properties on the flow field.

Assessing viability of extracorporeal preserved muscle transplants using external field stimulation: a novel tool to improve methods prolonging bridge-to-transplantation time

PubMed Central

Taeger, Christian D.; Friedrich, Oliver; Dragu, Adrian; Weigand, Annika; Hobe, Frieder; Drechsler, Caroline; Geppert, Carol I.; Arkudas, Andreas; Münch, Frank; Buchholz, Rainer; Pollmann, Charlotte; Schramm, Axel; Birkholz, Torsten; Horch, Raymund E.; Präbst, Konstantin

2015-01-01

Preventing ischemia-related cell damage is a priority when preserving tissue for transplantation. Perfusion protocols have been established for a variety of applications and proven to be superior to procedures used in clinical routine. Extracorporeal perfusion of muscle tissue though cumbersome is highly desirable since it is highly susceptible to ischemia-related damage. To show the efficacy of different perfusion protocols external field stimulation can be used to immediately visualize improvement or deterioration of the tissue during active and running perfusion protocols. This method has been used to show the superiority of extracorporeal perfusion using porcine rectus abdominis muscles perfused with heparinized saline solution. Perfused muscles showed statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. The combination of extracorporeal perfusion and external field stimulation may improve organ conservation research. PMID:26145230

Fuel Cell Backup Power Geographical Visualization Map (Fact Sheet)

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

Not Available

2012-12-01

This NREL Hydrogen and Fuel Cell Technical Highlight describes a time-lapse geographical visualization map of early market use of fuel cells for telecommunications backup power. The map synthesizes data being analyzed by NREL's Technology Validation team for the U.S. Department of Energy (DOE) Fuel Cell Technologies Program with DOE's publicly available annual summaries of electric disturbance events.

Visual selection and maintenance of the cell lines with high plant regeneration ability and low ploidy level in Dianthus acicularis by monitoring with flow cytometry analysis.

PubMed

Shiba, Tomonori; Mii, Masahiro

2005-12-01

Efficient plant regeneration system from cell suspension cultures was established in D. acicularis (2n=90) by monitoring ploidy level and visual selection of the cultures. The ploidy level of the cell cultures closely related to the shoot regeneration ability. The cell lines comprising original ploidy levels (2C+4C cells corresponding to DNA contents of G1 and G2 cells of diploid plant, respectively) showed high regeneration ability, whereas those containing the cells with 8C or higher DNA C-values showed low or no regeneration ability. The highly regenerable cell lines thus selected consisted of compact cell clumps with yellowish color and relatively moderate growth, suggesting that it is possible to select visually the highly regenerable cell lines with the original ploidy level. All the regenerated plantlets from the highly regenerable cell cultures exhibited normal phenotypes and no variations in ploidy level were observed by flow cytometry (FCM) analysis.

Visualization of Endoplasmic Reticulum and Mitochondria in Aurantiochytrium limacinum by the Expression of EGFP with Cell Organelle-Specific Targeting/Retaining Signals.

PubMed

Okino, Nozomu; Wakisaka, Hiroyoshi; Ishibashi, Yohei; Ito, Makoto

2018-04-01

Thraustochytrids are single cell marine eukaryotes that produce large amounts of polyunsaturated fatty acids such as docosahexaenoic acid. In the present study, we report the visualization of endoplasmic reticulum (ER) and mitochondria in a type strain of the thraustochytrid, Aurantiochytrium limacinum ATCC MYA-1381, using the enhanced green fluorescent protein (EGFP) with specific targeting/retaining signals. We expressed the egfp gene with ER targeting/retaining signals from A. limacinum calreticulin or BiP/GRP78 in the thraustochytrid, resulting in the distribution of EGFP signals at the perinuclear region and near lipid droplets. ER-Tracker™ Red, an authentic fluorescent probe for the visualization of ER in mammalian cells, also stained the same region. We observed small lipid droplets generated from the visualized ER in the early growth phase of cell culture. Expression of the egfp gene with the mitochondria targeting signal from A. limacinum cytochrome c oxidase resulted in the localization of EGFP near the plasma membrane. The distribution of EGFP signals coincided with that of MitoTracker® Red CMXRos, which is used to visualize mitochondria in eukaryotes. The ER and mitochondria of A. limacinum were visualized for the first time by EGFP with thraustochytrid cell organelle-specific targeting/retaining signals. These results will contribute to classification of the intracellular localization of proteins expressed in ER and mitochondria as well as analyses of these cell organelles in thraustochytrids.

Live Cell Visualization of Multiple Protein-Protein Interactions with BiFC Rainbow.

PubMed

Wang, Sheng; Ding, Miao; Xue, Boxin; Hou, Yingping; Sun, Yujie

2018-05-18

As one of the most powerful tools to visualize PPIs in living cells, bimolecular fluorescence complementation (BiFC) has gained great advancement during recent years, including deep tissue imaging with far-red or near-infrared fluorescent proteins or super-resolution imaging with photochromic fluorescent proteins. However, little progress has been made toward simultaneous detection and visualization of multiple PPIs in the same cell, mainly due to the spectral crosstalk. In this report, we developed novel BiFC assays based on large-Stokes-shift fluorescent proteins (LSS-FPs) to detect and visualize multiple PPIs in living cells. With the large excitation/emission spectral separation, LSS-FPs can be imaged together with normal Stokes shift fluorescent proteins to realize multicolor BiFC imaging using a simple illumination scheme. We also further demonstrated BiFC rainbow combining newly developed BiFC assays with previously established mCerulean/mVenus-based BiFC assays to achieve detection and visualization of four PPI pairs in the same cell. Additionally, we prove that with the complete spectral separation of mT-Sapphire and CyOFP1, LSS-FP-based BiFC assays can be readily combined with intensity-based FRET measurement to detect ternary protein complex formation with minimal spectral crosstalk. Thus, our newly developed LSS-FP-based BiFC assays not only expand the fluorescent protein toolbox available for BiFC but also facilitate the detection and visualization of multiple protein complex interactions in living cells.

Automatic cell identification and visualization using digital holographic microscopy with head mounted augmented reality devices.

PubMed

O'Connor, Timothy; Rawat, Siddharth; Markman, Adam; Javidi, Bahram

2018-03-01

We propose a compact imaging system that integrates an augmented reality head mounted device with digital holographic microscopy for automated cell identification and visualization. A shearing interferometer is used to produce holograms of biological cells, which are recorded using customized smart glasses containing an external camera. After image acquisition, segmentation is performed to isolate regions of interest containing biological cells in the field-of-view, followed by digital reconstruction of the cells, which is used to generate a three-dimensional (3D) pseudocolor optical path length profile. Morphological features are extracted from the cell's optical path length map, including mean optical path length, coefficient of variation, optical volume, projected area, projected area to optical volume ratio, cell skewness, and cell kurtosis. Classification is performed using the random forest classifier, support vector machines, and K-nearest neighbor, and the results are compared. Finally, the augmented reality device displays the cell's pseudocolor 3D rendering of its optical path length profile, extracted features, and the identified cell's type or class. The proposed system could allow a healthcare worker to quickly visualize cells using augmented reality smart glasses and extract the relevant information for rapid diagnosis. To the best of our knowledge, this is the first report on the integration of digital holographic microscopy with augmented reality devices for automated cell identification and visualization.

The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

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

Chen Bo; State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Science, Beijing 100101; Xia Jing

Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation- and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion. To investigate how orientation selectivity and direction selectivity of neurons are influenced by acute alcohol exposure in vivo, we used the extracellular single-unit recording technique to examine the response properties of neurons in primary visual cortex (A17) of adult cats. We found that alcohol reduces spontaneous activity, visual evoked unitmore » responses, the signal-to-noise ratio, and orientation selectivity of A17 cells. In addition, small but detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were observed after acute alcohol administration. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.« less

Auditory enhancement of visual perception at threshold depends on visual abilities.

PubMed

Caclin, Anne; Bouchet, Patrick; Djoulah, Farida; Pirat, Elodie; Pernier, Jacques; Giard, Marie-Hélène

2011-06-17

Whether or not multisensory interactions can improve detection thresholds, and thus widen the range of perceptible events is a long-standing debate. Here we revisit this question, by testing the influence of auditory stimuli on visual detection threshold, in subjects exhibiting a wide range of visual-only performance. Above the perceptual threshold, crossmodal interactions have indeed been reported to depend on the subject's performance when the modalities are presented in isolation. We thus tested normal-seeing subjects and short-sighted subjects wearing their usual glasses. We used a paradigm limiting potential shortcomings of previous studies: we chose a criterion-free threshold measurement procedure and precluded exogenous cueing effects by systematically presenting a visual cue whenever a visual target (a faint Gabor patch) might occur. Using this carefully controlled procedure, we found that concurrent sounds only improved visual detection thresholds in the sub-group of subjects exhibiting the poorest performance in the visual-only conditions. In these subjects, for oblique orientations of the visual stimuli (but not for vertical or horizontal targets), the auditory improvement was still present when visual detection was already helped with flanking visual stimuli generating a collinear facilitation effect. These findings highlight that crossmodal interactions are most efficient to improve perceptual performance when an isolated modality is deficient. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of Antipsychotic Drugs Haloperidol and Clozapine on Visual Responses of Retinal Ganglion Cells in a Rat Model of Retinitis Pigmentosa.

PubMed

Jensen, Ralph J

2016-12-01

In the P23H rat model of retinitis pigmentosa, the dopamine D2 receptor antagonists sulpiride and eticlopride appear to improve visual responses of retinal ganglion cells (RGCs) by increasing light sensitivity of RGCs and transforming abnormal, long-latency ON-center RGCs into OFF-center cells. Antipsychotic drugs are believed to mediate their therapeutic benefits by blocking D2 receptors. This investigation was conducted to test whether haloperidol (a typical antipsychotic drug) and clozapine (an atypical antipsychotic drug) could similarly alter the light responses of RGCs in the P23H rat retina. Extracellular recordings were made from RGCs in isolated P23H rat retinas. Responses of RGCs to flashes of light were evaluated before and during bath application of a drug. Both haloperidol and clozapine increased light sensitivity of RGCs on average by ∼0.3 log unit. For those ON-center RGCs that exhibit an abnormally long-latency response to the onset of a small spot of light, both haloperidol and clozapine brought out a short-latency OFF response and markedly reduced the long-latency ON response. The selective serotonin 5-HT2A antagonist MDL 100907 had similar effects on RGCs. The effects of haloperidol on light responses of RGCs can be explained by its D2 receptor antagonism. The effects of clozapine on light responses of RGCs on the other hand may largely be due to its 5-HT2A receptor antagonism. Overall, the results suggest that antipsychotic drugs may be useful in improving vision in patients with retinitis pigmentosa.

Absence of Visual Input Results in the Disruption of Grid Cell Firing in the Mouse.

PubMed

Chen, Guifen; Manson, Daniel; Cacucci, Francesca; Wills, Thomas Joseph

2016-09-12

Grid cells are spatially modulated neurons within the medial entorhinal cortex whose firing fields are arranged at the vertices of tessellating equilateral triangles [1]. The exquisite periodicity of their firing has led to the suggestion that they represent a path integration signal, tracking the organism's position by integrating speed and direction of movement [2-10]. External sensory inputs are required to reset any errors that the path integrator would inevitably accumulate. Here we probe the nature of the external sensory inputs required to sustain grid firing, by recording grid cells as mice explore familiar environments in complete darkness. The absence of visual cues results in a significant disruption of grid cell firing patterns, even when the quality of the directional information provided by head direction cells is largely preserved. Darkness alters the expression of velocity signaling within the entorhinal cortex, with changes evident in grid cell firing rate and the local field potential theta frequency. Short-term (<1.5 s) spike timing relationships between grid cell pairs are preserved in the dark, indicating that network patterns of excitatory and inhibitory coupling between grid cells exist independently of visual input and of spatially periodic firing. However, we find no evidence of preserved hexagonal symmetry in the spatial firing of single grid cells at comparable short timescales. Taken together, these results demonstrate that visual input is required to sustain grid cell periodicity and stability in mice and suggest that grid cells in mice cannot perform accurate path integration in the absence of reliable visual cues. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Femtoelectron-Based Terahertz Imaging of Hydration State in a Proton Exchange Membrane Fuel Cell

NASA Astrophysics Data System (ADS)

Buaphad, P.; Thamboon, P.; Kangrang, N.; Rhodes, M. W.; Thongbai, C.

2015-08-01

Imbalanced water management in a proton exchange membrane (PEM) fuel cell significantly reduces the cell performance and durability. Visualization of water distribution and transport can provide greater comprehension toward optimization of the PEM fuel cell. In this work, we are interested in water flooding issues that occurred in flow channels on cathode side of the PEM fuel cell. The sample cell was fabricated with addition of a transparent acrylic window allowing light access and observed the process of flooding formation (in situ) via a CCD camera. We then explore potential use of terahertz (THz) imaging, consisting of femtoelectron-based THz source and off-angle reflective-mode imaging, to identify water presence in the sample cell. We present simulations of two hydration states (water and nonwater area), which are in agreement with the THz image results. A line-scan plot is utilized for quantitative analysis and for defining spatial resolution of the image. Implementing metal mesh filtering can improve spatial resolution of our THz imaging system.

Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo.

PubMed

Thurber, Greg M; Yang, Katy S; Reiner, Thomas; Kohler, Rainer H; Sorger, Peter; Mitchison, Tim; Weissleder, Ralph

2013-01-01

Pharmacokinetic analysis at the organ level provides insight into how drugs distribute throughout the body, but cannot explain how drugs work at the cellular level. Here we demonstrate in vivo single-cell pharmacokinetic imaging of PARP-1 inhibitors and model drug behaviour under varying conditions. We visualize intracellular kinetics of the PARP-1 inhibitor distribution in real time, showing that PARP-1 inhibitors reach their cellular target compartment, the nucleus, within minutes in vivo both in cancer and normal cells in various cancer models. We also use these data to validate predictive finite element modelling. Our theoretical and experimental data indicate that tumour cells are exposed to sufficiently high PARP-1 inhibitor concentrations in vivo and suggest that drug inefficiency is likely related to proteomic heterogeneity or insensitivity of cancer cells to DNA-repair inhibition. This suggests that single-cell pharmacokinetic imaging and derived modelling improve our understanding of drug action at single-cell resolution in vivo.

Correspondence between visual and electrical input filters of ON and OFF mouse retinal ganglion cells

NASA Astrophysics Data System (ADS)

Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

2017-08-01

Objective. Over the past two decades retinal prostheses have made major strides in restoring functional vision to patients blinded by diseases such as retinitis pigmentosa. Presently, implants use single pulses to activate the retina. Though this stimulation paradigm has proved beneficial to patients, an unresolved problem is the inability to selectively stimulate the on and off visual pathways. To this end our goal was to test, using white noise, voltage-controlled, cathodic, monophasic pulse stimulation, whether different retinal ganglion cell (RGC) types in the wild type retina have different electrical input filters. This is an important precursor to addressing pathway-selective stimulation. Approach. Using full-field visual flash and electrical and visual Gaussian noise stimulation, combined with the technique of spike-triggered averaging (STA), we calculate the electrical and visual input filters for different types of RGCs (classified as on, off or on-off based on their response to the flash stimuli). Main results. Examining the STAs, we found that the spiking activity of on cells during electrical stimulation correlates with a decrease in the voltage magnitude preceding a spike, while the spiking activity of off cells correlates with an increase in the voltage preceding a spike. No electrical preference was found for on-off cells. Comparing STAs of wild type and rd10 mice revealed narrower electrical STA deflections with shorter latencies in rd10. Significance. This study is the first comparison of visual cell types and their corresponding temporal electrical input filters in the retina. The altered input filters in degenerated rd10 retinas are consistent with photoreceptor stimulation underlying visual type-specific electrical STA shapes in wild type retina. It is therefore conceivable that existing implants could target partially degenerated photoreceptors that have only lost their outer segments, but not somas, to selectively activate the on and off visual pathways.

Three-dimensional visualization of nanostructured surfaces and bacterial attachment using Autodesk® Maya®.

PubMed

Boshkovikj, Veselin; Fluke, Christopher J; Crawford, Russell J; Ivanova, Elena P

2014-02-28

There has been a growing interest in understanding the ways in which bacteria interact with nano-structured surfaces. As a result, there is a need for innovative approaches to enable researchers to visualize the biological processes taking place, despite the fact that it is not possible to directly observe these processes. We present a novel approach for the three-dimensional visualization of bacterial interactions with nano-structured surfaces using the software package Autodesk Maya. Our approach comprises a semi-automated stage, where actual surface topographic parameters, obtained using an atomic force microscope, are imported into Maya via a custom Python script, followed by a 'creative stage', where the bacterial cells and their interactions with the surfaces are visualized using available experimental data. The 'Dynamics' and 'nDynamics' capabilities of the Maya software allowed the construction and visualization of plausible interaction scenarios. This capability provides a practical aid to knowledge discovery, assists in the dissemination of research results, and provides an opportunity for an improved public understanding. We validated our approach by graphically depicting the interactions between the two bacteria being used for modeling purposes, Staphylococcus aureus and Pseudomonas aeruginosa, with different titanium substrate surfaces that are routinely used in the production of biomedical devices.

Three-dimensional visualization of nanostructured surfaces and bacterial attachment using Autodesk® Maya®

NASA Astrophysics Data System (ADS)

Boshkovikj, Veselin; Fluke, Christopher J.; Crawford, Russell J.; Ivanova, Elena P.

2014-02-01

There has been a growing interest in understanding the ways in which bacteria interact with nano-structured surfaces. As a result, there is a need for innovative approaches to enable researchers to visualize the biological processes taking place, despite the fact that it is not possible to directly observe these processes. We present a novel approach for the three-dimensional visualization of bacterial interactions with nano-structured surfaces using the software package Autodesk Maya. Our approach comprises a semi-automated stage, where actual surface topographic parameters, obtained using an atomic force microscope, are imported into Maya via a custom Python script, followed by a `creative stage', where the bacterial cells and their interactions with the surfaces are visualized using available experimental data. The `Dynamics' and `nDynamics' capabilities of the Maya software allowed the construction and visualization of plausible interaction scenarios. This capability provides a practical aid to knowledge discovery, assists in the dissemination of research results, and provides an opportunity for an improved public understanding. We validated our approach by graphically depicting the interactions between the two bacteria being used for modeling purposes, Staphylococcus aureus and Pseudomonas aeruginosa, with different titanium substrate surfaces that are routinely used in the production of biomedical devices.

Three-dimensional visualization of nanostructured surfaces and bacterial attachment using Autodesk® Maya®

PubMed Central

Boshkovikj, Veselin; Fluke, Christopher J.; Crawford, Russell J.; Ivanova, Elena P.

2014-01-01

There has been a growing interest in understanding the ways in which bacteria interact with nano-structured surfaces. As a result, there is a need for innovative approaches to enable researchers to visualize the biological processes taking place, despite the fact that it is not possible to directly observe these processes. We present a novel approach for the three-dimensional visualization of bacterial interactions with nano-structured surfaces using the software package Autodesk Maya. Our approach comprises a semi-automated stage, where actual surface topographic parameters, obtained using an atomic force microscope, are imported into Maya via a custom Python script, followed by a ‘creative stage', where the bacterial cells and their interactions with the surfaces are visualized using available experimental data. The ‘Dynamics' and ‘nDynamics' capabilities of the Maya software allowed the construction and visualization of plausible interaction scenarios. This capability provides a practical aid to knowledge discovery, assists in the dissemination of research results, and provides an opportunity for an improved public understanding. We validated our approach by graphically depicting the interactions between the two bacteria being used for modeling purposes, Staphylococcus aureus and Pseudomonas aeruginosa, with different titanium substrate surfaces that are routinely used in the production of biomedical devices. PMID:24577105

Drug/Cell-line Browser: interactive canvas visualization of cancer drug/cell-line viability assay datasets.

PubMed

Duan, Qiaonan; Wang, Zichen; Fernandez, Nicolas F; Rouillard, Andrew D; Tan, Christopher M; Benes, Cyril H; Ma'ayan, Avi

2014-11-15

Recently, several high profile studies collected cell viability data from panels of cancer cell lines treated with many drugs applied at different concentrations. Such drug sensitivity data for cancer cell lines provide suggestive treatments for different types and subtypes of cancer. Visualization of these datasets can reveal patterns that may not be obvious by examining the data without such efforts. Here we introduce Drug/Cell-line Browser (DCB), an online interactive HTML5 data visualization tool for interacting with three of the recently published datasets of cancer cell lines/drug-viability studies. DCB uses clustering and canvas visualization of the drugs and the cell lines, as well as a bar graph that summarizes drug effectiveness for the tissue of origin or the cancer subtypes for single or multiple drugs. DCB can help in understanding drug response patterns and prioritizing drug/cancer cell line interactions by tissue of origin or cancer subtype. DCB is an open source Web-based tool that is freely available at: http://www.maayanlab.net/LINCS/DCB CONTACT: avi.maayan@mssm.edu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A matter of time: improvement of visual temporal processing during training-induced restoration of light detection performance

PubMed Central

Poggel, Dorothe A.; Treutwein, Bernhard; Sabel, Bernhard A.; Strasburger, Hans

2015-01-01

The issue of how basic sensory and temporal processing are related is still unresolved. We studied temporal processing, as assessed by simple visual reaction times (RT) and double-pulse resolution (DPR), in patients with partial vision loss after visual pathway lesions and investigated whether vision restoration training (VRT), a training program designed to improve light detection performance, would also affect temporal processing. Perimetric and campimetric visual field tests as well as maps of DPR thresholds and RT were acquired before and after a 3 months training period with VRT. Patient performance was compared to that of age-matched healthy subjects. Intact visual field size increased during training. Averaged across the entire visual field, DPR remained constant while RT improved slightly. However, in transition zones between the blind and intact areas (areas of residual vision) where patients had shown between 20 and 80% of stimulus detection probability in pre-training visual field tests, both DPR and RT improved markedly. The magnitude of improvement depended on the defect depth (or degree of intactness) of the respective region at baseline. Inter-individual training outcome variability was very high, with some patients showing little change and others showing performance approaching that of healthy controls. Training-induced improvement of light detection in patients with visual field loss thus generalized to dynamic visual functions. The findings suggest that similar neural mechanisms may underlie the impairment and subsequent training-induced functional recovery of both light detection and temporal processing. PMID:25717307

3D surface reconstruction and visualization of the Drosophila wing imaginal disc at cellular resolution

NASA Astrophysics Data System (ADS)

Bai, Linge; Widmann, Thomas; Jülicher, Frank; Dahmann, Christian; Breen, David

2013-01-01

Quantifying and visualizing the shape of developing biological tissues provide information about the morphogenetic processes in multicellular organisms. The size and shape of biological tissues depend on the number, size, shape, and arrangement of the constituting cells. To better understand the mechanisms that guide tissues into their final shape, it is important to investigate the cellular arrangement within tissues. Here we present a data processing pipeline to generate 3D volumetric surface models of epithelial tissues, as well as geometric descriptions of the tissues' apical cell cross-sections. The data processing pipeline includes image acquisition, editing, processing and analysis, 2D cell mesh generation, 3D contourbased surface reconstruction, cell mesh projection, followed by geometric calculations and color-based visualization of morphological parameters. In their first utilization we have applied these procedures to construct a 3D volumetric surface model at cellular resolution of the wing imaginal disc of Drosophila melanogaster. The ultimate goal of the reported effort is to produce tools for the creation of detailed 3D geometric models of the individual cells in epithelial tissues. To date, 3D volumetric surface models of the whole wing imaginal disc have been created, and the apicolateral cell boundaries have been identified, allowing for the calculation and visualization of cell parameters, e.g. apical cross-sectional area of cells. The calculation and visualization of morphological parameters show position-dependent patterns of cell shape in the wing imaginal disc. Our procedures should offer a general data processing pipeline for the construction of 3D volumetric surface models of a wide variety of epithelial tissues.

Digital Museum of Retinal Ganglion Cells with Dense Anatomy and Physiology.

PubMed

Bae, J Alexander; Mu, Shang; Kim, Jinseop S; Turner, Nicholas L; Tartavull, Ignacio; Kemnitz, Nico; Jordan, Chris S; Norton, Alex D; Silversmith, William M; Prentki, Rachel; Sorek, Marissa; David, Celia; Jones, Devon L; Bland, Doug; Sterling, Amy L R; Park, Jungman; Briggman, Kevin L; Seung, H Sebastian

2018-05-17

When 3D electron microscopy and calcium imaging are used to investigate the structure and function of neural circuits, the resulting datasets pose new challenges of visualization and interpretation. Here, we present a new kind of digital resource that encompasses almost 400 ganglion cells from a single patch of mouse retina. An online "museum" provides a 3D interactive view of each cell's anatomy, as well as graphs of its visual responses. The resource reveals two aspects of the retina's inner plexiform layer: an arbor segregation principle governing structure along the light axis and a density conservation principle governing structure in the tangential plane. Structure is related to visual function; ganglion cells with arbors near the layer of ganglion cell somas are more sustained in their visual responses on average. Our methods are potentially applicable to dense maps of neuronal anatomy and physiology in other parts of the nervous system. Copyright © 2018 Elsevier Inc. All rights reserved.

Visualization of risk structures for interactive planning of image guided radiofrequency ablation of liver tumors

NASA Astrophysics Data System (ADS)

Rieder, Christian; Schwier, Michael; Weihusen, Andreas; Zidowitz, Stephan; Peitgen, Heinz-Otto

2009-02-01

Image guided radiofrequency ablation (RFA) is becoming a standard procedure as a minimally invasive method for tumor treatment in the clinical routine. The visualization of pathological tissue and potential risk structures like vessels or important organs gives essential support in image guided pre-interventional RFA planning. In this work our aim is to present novel visualization techniques for interactive RFA planning to support the physician with spatial information of pathological structures as well as the finding of trajectories without harming vitally important tissue. Furthermore, we illustrate three-dimensional applicator models of different manufactures combined with corresponding ablation areas in homogenous tissue, as specified by the manufacturers, to enhance the estimated amount of cell destruction caused by ablation. The visualization techniques are embedded in a workflow oriented application, designed for the use in the clinical routine. To allow a high-quality volume rendering we integrated a visualization method using the fuzzy c-means algorithm. This method automatically defines a transfer function for volume visualization of vessels without the need of a segmentation mask. However, insufficient visualization results of the displayed vessels caused by low data quality can be improved using local vessel segmentation in the vicinity of the lesion. We also provide an interactive segmentation technique of liver tumors for the volumetric measurement and for the visualization of pathological tissue combined with anatomical structures. In order to support coagulation estimation with respect to the heat-sink effect of the cooling blood flow which decreases thermal ablation, a numerical simulation of the heat distribution is provided.

Visualization experiments on steam injection in Hele-Shaw cells

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

Kong, Xianli; Haghighi, M.; Yortsos, Y.C.

1992-03-01

Flow visualization experiments have been successfully employed in reservoir engineering research for many years. They involve 2-D geometries in transparent Hele-Shaw cells and glass micromodels. Although much work has been done on immiscible flows (drainage or imbibition), visualization of steamfloods, which constitute a major part of current EOR methods, has not been attempted to data. In this paper, we present experimental results on steam injection in a transparent, pyrex glass Hele-Shaw cell. Both synthetic (Dutrex 739) and natural heavy oils were used under a variety of conditions, including effects of gravity.

The retinal morphology and retinal histochemistry of a twilight fish Corydoras paleatus (J.).

PubMed

Yew, D T; Woo, H H

1976-01-01

1. The retinas of Corydoras paleatus were studied by histology (HE) and histochemistry (PAS and Nucleic acid). 2. Three types of visual cells were observed, namely rod, single cone and twin cone. All of them are PAS positive. 3. The histochemical PAS pattern of these visual cells differs from those species which are not of a twilight habitat. 4. Significant amount of RNA were not detected in the inner segments of visual cells in this species indicating a possible slow renewal of outer segments.

Using "Chromosomal Socks" to Demonstrate Ploidy in Mitosis and Meiosis

ERIC Educational Resources Information Center

Chinnici, Joseph P.; Neth, Somalin Zaroh; Sherman, Leah R.

2006-01-01

Today, many biology instructors use visual models to help students understand abstract concepts like cell division. For all biology instructors, dealing with student misconceptions of cell division may seem hopeless at times--even after using visual models. Although student errors in cell division are built around the three key events of cell…

Imaging Stem Cells Implanted in Infarcted Myocardium

PubMed Central

Zhou, Rong; Acton, Paul D.; Ferrari, Victor A.

2008-01-01

Stem cell–based cellular cardiomyoplasty represents a promising therapy for myocardial infarction. Noninvasive imaging techniques would allow the evaluation of survival, migration, and differentiation status of implanted stem cells in the same subject over time. This review describes methods for cell visualization using several corresponding noninvasive imaging modalities, including magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and bioluminescent imaging. Reporter-based cell visualization is compared with direct cell labeling for short- and long-term cell tracking. PMID:17112999

Alpha-galactosidase versus active charcoal for improving sonographic visualization of abdominal organs in patients with excessive intestinal gas

PubMed Central

Maconi, G.; Bolzacchini, E.; Radice, E.; Marzocchi, M.; Badini, M.

2012-01-01

Background and aims Intestinal gas is a frequent cause of poor visualization during gastrointestinal ultrasound (US). The enzyme alpha-galactosidase may reduce intestinal gas production, thereby improving abdominal US visualization. We compared the efficacies of alpha-galactosidase and active charcoal in improving US visualization in patients with previous unsatisfactory abdominal US scans caused by excessive intestinal gas. Materials and methods: 45 patients with poor visualization of at least one target organ: pancreas, hepatic lobes (score 0–2) or common bile duct (CBD) (score 0–1) were enrolled in a prospective randomized, crossover, observer-blinded study. The patients received alpha-galactosidase (Sinaire Forte, Promefarm, Milan, Italy) 600 GalU t.i.d. for 2 days before abdominal US plus 900 GalU the morning of exam or active charcoal 448 mg t.i.d., for 2 days before the exam plus 672 mg the morning of the exam. Visualization was graded as follows: 0 = none (complete gas interference); 1 = severe interference, 2 = moderate interference, 3 = mild interference; 4 = complete (no gas interference). Results: 42 patients completed the study. Both alpha-galactosidase and active charcoal improved the visualization of target organs. Visualization of the right hepatic lobe, CBD and pancreatic tail was significantly improved (vs. baseline) only by alpha-galactosidase (p < 0.01). Scores ≥3 for all parts of the pancreas and both hepatic lobes were achieved in only 12.5% of the patients after both treatments. Both products were well tolerated. Conclusion: Alpha-galactosidase and active charcoal can improve US visualization of abdominal organs in patients whose scans are frequently unsatisfactory due to excessive intestinal gas. Visualization of the pancreatic tail and right hepatic lobe was significantly improved only by alpha-galactosidase. However, both treatments allowed adequate visualization of all target organs during the same examination only in a few patients. PMID:23730387

Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model.

PubMed

Georges, Joseph F; Liu, Xiaowei; Eschbacher, Jennifer; Nichols, Joshua; Mooney, Michael A; Joy, Anna; Spetzler, Robert F; Feuerstein, Burt G; Preul, Mark C; Anderson, Trent; Yan, Hao; Nakaji, Peter

2015-01-01

Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

Outcomes of cataract surgery in eyes with a low corneal endothelial cell density.

PubMed

Yamazoe, Katsuya; Yamaguchi, Takefumi; Hotta, Kazuki; Satake, Yoshiyuki; Konomi, Kenji; Den, Seika; Shimazaki, Jun

2011-12-01

To evaluate the surgical outcomes of cataract surgery in eyes with a low preoperative corneal endothelial cell density (ECD) and analyze factors affecting the prognosis. Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan. Noncomparative case series. Eyes with a preoperative ECD of less than 1000 cells/mm(2) that had cataract surgery between 2006 and 2010 were identified. Standard phacoemulsification with intraocular lenses was performed using the soft-shell technique. The rate of endothelial cell loss, incidence of bullous keratopathy, and risk factors were retrospectively assessed. Sixty-one eyes (53 patients) with a low preoperative ECD were identified. Preoperative diagnoses or factors regarded as causing endothelial cell loss included Fuchs dystrophy (20 eyes), laser iridotomy (16 eyes), keratoplasty (10 eyes), traumatic injury (3 eyes), trabeculectomy (3 eyes), corneal endotheliitis (2 eyes), and other (7 eyes). The corrected distance visual acuity improved from 0.59 ± 0.49 logMAR preoperatively to 0.32 ± 0.48 logMAR postoperatively (P<.001). The mean ECD was 693 ± 172 cells/mm(2) and 611 ± 203 cells/mm(2), respectively (P=.001). The mean rate of endothelial cell loss was 11.5% ± 23.4%. Greater ECD loss was associated with a shorter axial length (AL) (<23.0 mm) and diabetes mellitus. Bullous keratopathy developed in 9 eyes (14.8%) and was associated with posterior capsule rupture. The results suggest that modern techniques for cataract surgery provide excellent visual rehabilitation in many patients with a low preoperative ECD. Shorter AL, diabetes mellitus, and posterior capsule rupture were risk factors for greater ECD loss and bullous keratopathy. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Visualization Improves Supraclavicular Access to the Subclavian Vein in a Mixed Reality Simulator.

PubMed

Sappenfield, Joshua Warren; Smith, William Brit; Cooper, Lou Ann; Lizdas, David; Gonsalves, Drew B; Gravenstein, Nikolaus; Lampotang, Samsun; Robinson, Albert R

2018-07-01

We investigated whether visual augmentation (3D, real-time, color visualization) of a procedural simulator improved performance during training in the supraclavicular approach to the subclavian vein, not as widely known or used as its infraclavicular counterpart. To train anesthesiology residents to access a central vein, a mixed reality simulator with emulated ultrasound imaging was created using an anatomically authentic, 3D-printed, physical mannequin based on a computed tomographic scan of an actual human. The simulator has a corresponding 3D virtual model of the neck and upper chest anatomy. Hand-held instruments such as a needle, an ultrasound probe, and a virtual camera controller are directly manipulated by the trainee and tracked and recorded with submillimeter resolution via miniature, 6 degrees of freedom magnetic sensors. After Institutional Review Board approval, 69 anesthesiology residents and faculty were enrolled and received scripted instructions on how to perform subclavian venous access using the supraclavicular approach based on anatomic landmarks. The volunteers were randomized into 2 cohorts. The first used real-time 3D visualization concurrently with trial 1, but not during trial 2. The second did not use real-time 3D visualization concurrently with trial 1 or 2. However, after trial 2, they observed a 3D visualization playback of trial 2 before performing trial 3 without visualization. An automated scoring system based on time, success, and errors/complications generated objective performance scores. Nonparametric statistical methods were used to compare the scores between subsequent trials, differences between groups (real-time visualization versus no visualization versus delayed visualization), and improvement in scores between trials within groups. Although the real-time visualization group demonstrated significantly better performance than the delayed visualization group on trial 1 (P = .01), there was no difference in gain scores, between performance on the first trial and performance on the final trial, that were dependent on group (P = .13). In the delayed visualization group, the difference in performance between trial 1 and trial 2 was not significant (P = .09); reviewing performance on trial 2 before trial 3 resulted in improved performance when compared to trial 1 (P < .0001). There was no significant difference in median scores (P = .13) between the real-time visualization and delayed visualization groups for the last trial after both groups had received visualization. Participants reported a significant improvement in confidence in performing supraclavicular access to the subclavian vein. Standard deviations of scores, a measure of performance variability, decreased in the delayed visualization group after viewing the visualization. Real-time visual augmentation (3D visualization) in the mixed reality simulator improved performance during supraclavicular access to the subclavian vein. No difference was seen in the final trial of the group that received real-time visualization compared to the group that had delayed visualization playback of their prior attempt. Training with the mixed reality simulator improved participant confidence in performing an unfamiliar technique.

Wavelet decomposition analysis in the two-flash multifocal ERG in early glaucoma: a comparison to ganglion cell analysis and visual field.

PubMed

Brandao, Livia M; Monhart, Matthias; Schötzau, Andreas; Ledolter, Anna A; Palmowski-Wolfe, Anja M

2017-08-01

To further improve analysis of the two-flash multifocal electroretinogram (2F-mfERG) in glaucoma in regard to structure-function analysis, using discrete wavelet transform (DWT) analysis. Sixty subjects [35 controls and 25 primary open-angle glaucoma (POAG)] underwent 2F-mfERG. Responses were analyzed with the DWT. The DWT level that could best separate POAG from controls was compared to the root-mean-square (RMS) calculations previously used in the analysis of the 2F-mfERG. In a subgroup analysis, structure-function correlation was assessed between DWT, optical coherence tomography and automated perimetry (mf103 customized pattern) for the central 15°. Frequency level 4 of the wavelet variance analysis (144 Hz, WVA-144) was most sensitive (p < 0.003). It correlated positively with RMS but had a better AUC. Positive relations were found between visual field, WVA-144 and GCIPL thickness. The highest predictive factor for glaucoma diagnostic was seen in the GCIPL, but this improved further by adding the mean sensitivity and WVA-144. mfERG using WVA analysis improves glaucoma diagnosis, especially when combined with GCIPL and MS.

Quantitative visualization of synchronized insulin secretion from 3D-cultured cells

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

Suzuki, Takahiro; Kanamori, Takao; Inouye, Satoshi

Quantitative visualization of synchronized insulin secretion was performed in an isolated rat pancreatic islet and a spheroid of rat pancreatic beta cell line using a method of video-rate bioluminescence imaging. Video-rate images of insulin secretion from 3D-cultured cells were obtained by expressing the fusion protein of insulin and Gaussia luciferase (Insulin-GLase). A subclonal rat INS-1E cell line stably expressing Insulin-GLase, named iGL, was established and a cluster of iGL cells showed oscillatory insulin secretion that was completely synchronized in response to high glucose. Furthermore, we demonstrated the effect of an antidiabetic drug, glibenclamide, on synchronized insulin secretion from 2D- andmore » 3D-cultured iGL cells. The amount of secreted Insulin-GLase from iGL cells was also determined by a luminometer. Thus, our bioluminescence imaging method could generally be used for investigating protein secretion from living 3D-cultured cells. In addition, iGL cell line would be valuable for evaluating antidiabetic drugs. - Highlights: • An imaging method for protein secretion from 3D-cultured cells was established. • The fused protein of insulin to GLase, Insulin-GLase, was used as a reporter. • Synchronous insulin secretion was visualized in rat islets and spheroidal beta cells. • A rat beta cell line stably expressing Insulin-GLase, named iGL, was established. • Effect of an antidiabetic drug on insulin secretion was visualized in iGL cells.« less

Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

PubMed

Leung, Loh-Shan B; Neal, Joel W; Wakelee, Heather A; Sequist, Lecia V; Marmor, Michael F

2015-10-01

To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. Retrospective observational case series. Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.

An Adult Case of Fulminant Mumps Keratitis With Positive Viral RNA in Aqueous Humor Detected by RT-PCR.

PubMed

Shibata, Teppei; Takahashi, Yoriko; Okamoto, Ayako; Sasaki, Hiroshi; Kitagawa, Kazuko

2016-04-01

To report an adult case of mumps keratitis with mumps virus in aqueous humor and decreased corneal endothelial cell density. Case report. A 60-year-old female with a 39°C fever and bilateral parotid swelling diagnosed with mumps and treated for photophobia, pain, redness, and decreased vision in 1 eye, was referred to our hospital when her condition deteriorated despite receiving betamethasone phosphate instillation and antiglaucoma agents for elevated intraocular pressure (52 mm Hg) and iritis. Her right eye was normal, whereas her left eye showed 20/400 visual acuity, 21 mm Hg intraocular pressure, ciliary injection and edema, opacity, and Descemet folds in the entire cornea. Round white keratic precipitates were present on the posterior corneal surface, whereas anterior chamber cells could not be examined in detail because of corneal edema. Mumps virus was detected by reverse transcriptase polymerase chain reaction in an aqueous humor sample taken at the time of admission. Following diagnosis of keratitis, administration of 30 mg oral prednisolone daily and frequent instillation of betamethasone phosphate steadily improved her corneal edema and opacity. In her left eye, visual acuity recovered to 20/16 and keratitis was resolved at 4 weeks; however, corneal endothelial cell density was significantly decreased to less than 400 per square millimeter. Mumps keratitis may cause severe corneal endothelial cell loss.

Clinically significant differences in the visual analog pain scale in acute vasoocclusive sickle cell crisis.

PubMed

Lopez, Bernard L; Flenders, Pamela; Davis-Moon, Linda; Corbin, Theodore; Ballas, Samir K

2007-01-01

This study sought to determine the minimum clinically significant change in the visual analog scale (VAS) during the Emergency Department (ED) treatment of adult vasoocclusive sickle cell crisis (VOC). Sickle cell anemia patients presenting to the ED with their typical VOC pain had a 100 mm VAS administered prior to each of up to three standard analgesic injections administered as part of a treatment protocol. At each assessment, subjects were asked to describe their pain as "much better," a "little better," "the same," "a little worse," or "much worse." The change in the VAS (DeltaVAS) between assessments was measured. The main outcome of the measurement was change in the VAS associated with a description of a change in pain of "a little less" or "a little more." Seventy four subjects presented with initially high pain scores [VAS = 79.47 mm, 95% confidence interval (CI) = 75.99 to 82.95 mm]. In the "little better/little worse" combined group, the DeltaVAS was 13.5 mm (95% CI = 11.25 cm to 15.74 cm). A change in the 100 mm VAS of 13.5 mm is the minimum clinically significant change during ED treatment of VOC. A DeltaVAS <13.5 mm may not be clinically important. This finding may assist the clinician in the assessment of pain improvement for adult sickle cell patients with VOC.

Traumatic Brain Injury and Hyperbaric Oxygen Therapy Dawn of a New Day

DTIC Science & Technology

2017-09-07

Both used to test for differences between groups • No significant statistical difference between groups, but both groups improved • Relative...George Wolf, Laura M . Baugh, Christine M. Schubert Kabban, Michael F. Richards, Jennifer Prye • Individual test scores • ImPACT: • visual memory and...Stem cells collected prior to series, after 15 exposures. after 30 exposure series, and 6 weel< post series. • 13 subjects from 1.3 ATA air and 15

Computer Vision Syndrome.

PubMed

Randolph, Susan A

2017-07-01

With the increased use of electronic devices with visual displays, computer vision syndrome is becoming a major public health issue. Improving the visual status of workers using computers results in greater productivity in the workplace and improved visual comfort.

Promising New Photon Detection Concepts for High-Resolution Clinical and Preclinical PET

PubMed Central

Levin, Craig S.

2013-01-01

The ability of PET to visualize and quantify regions of low concentration of PET tracer representing subtle cellular and molecular signatures of disease depends on relatively complex biochemical, biologic, and physiologic factors that are challenging to control, as well as on instrumentation performance parameters that are, in principle, still possible to improve on. Thus, advances to the latter can somewhat offset barriers of the former. PET system performance parameters such as spatial resolution, contrast resolution, and photon sensitivity contribute significantly to PET’s ability to visualize and quantify lower concentrations of signal in the presence of background. In this report we present some technology innovations under investigation toward improving these PET system performance parameters. We focus particularly on a promising advance known as 3-dimensional position-sensitive detectors, which are detectors capable of distinguishing and measuring the position, energy, and arrival time of individual interactions of multi-interaction photon events in 3 dimensions. If successful, these new strategies enable enhancements such as the detection of fewer diseased cells in tissue or the ability to characterize lower-abundance molecular targets within cells. Translating these advanced capabilities to the clinic might allow expansion of PET’s roles in disease management, perhaps to earlier stages of disease. In preclinical research, such enhancements enable more sensitive and accurate studies of disease biology in living subjects. PMID:22302960

Long-Term Outcomes of Cultivated Limbal Epithelial Transplantation: Evaluation and Comparison of Results in Children and Adults

PubMed Central

Ganger, Anita; Vanathi, M.; Mohanty, Sujata; Tandon, Radhika

2015-01-01

Purpose. To compare the long-term clinical outcomes of cultivated limbal epithelial transplantation (CLET) in children and adults with limbal stem cell deficiency. Design. Retrospective case series. Methods. Case records of patients with limbal stem cell deficiency (LSCD) who underwent CLET from April 2004 to December 2014 were studied. Outcome measures were compared in terms of anatomical success and visual improvement. Parameters for total anatomical success were avascular, epithelized, and clinically stable corneal surface without conjunctivalization, whereas partial anatomical success was considered when mild vascularization (sparing centre of cornea) and mild conjunctivalization were noted along with complete epithelization. Results. A total of 62 cases underwent the CLET procedure: 38 (61.3%) were children and 24 (38.7%) were adults. Patients with unilateral LSCD (33 children and 21 adults) had autografts and those with bilateral LSCD (5 children and 3 adults) had allografts. Amongst the 54 autografts partial and total anatomical success were noted in 21.2% and 66.6% children, respectively, and 19.0% and 80.9% in adults, respectively (p value 0.23). Visual improvement of 1 line and ≥2 lines was seen in 57.5% and 21.2% children, respectively, and 38% and 38% in adults, respectively (p value 0.31). Conclusion. Cultivated limbal epithelial transplantation gives good long-term results in patients with LSCD and the outcomes are comparable in children and adults. PMID:26770973

Corneal collagen crosslinking for corneal ectasia of post-LASIK: one-year results

PubMed Central

Li, Gang; Fan, Zheng-Jun; Peng, Xiu-Jun

2012-01-01

AIM To evaluate the efficacy and safety of corneal collagen crosslinking (CXL) to prevent the progression of post-laser in situ keratomileusis (LASIK) corneal ectasia. METHODS In a prospective, nonrandomized, single-centre study, CXL was performed in 20 eyes of 11 patients who had LASIK for myopic astigmatism and subsequently developed keratectasia.The procedure included instillation of 0.1% riboflavin-20% dextrane solution 30 minutes before UVA irradiation and every 5 minutes for an additional 30 minutes during irradiation. The eyes were evaluated preoperatively and at 1-, 3-, 6-, and 12-month intervals. The complete ophthalmologic examination comprised uncorrected visual acuity, best spectacle-corrected visual acuity, endothelial cell count, ultrasound pachymetry, corneal topography, and in vivo confocal microscopy. RESULTS CXL appeared to stabilise or partially reverse the progression of post-LASIK corneal ectasia without apparent complication in our cohort. UCVA and BCVA improvements were statistically significant(P<0.05) beyond 12 months after surgery (improvement of 0.07 and 0.13 logMAR at 1 year, respectively). Mean baseline flattest meridian keratometry and mean steepest meridian keratometry reduction (improvement of 2.00 and 1.50 diopters(D), respectively) were statistically significant (P<0.05) at 12 months postoperatively. At 1 year after CXL, mean endothelial cell count did not deteriorate. Mean thinnest cornea pachymetry increased significantly. CONCLUSION The results of the study showed a long-term stability of post-LASIK corneal ectasia after crosslinking without relevant side effects. It seems to be a safe and promising procedure to stop the progression of post-LASIK keratectasia, thereby avoiding or delaying keratoplasty. PMID:22762048

Value-cell bar charts for visualizing large transaction data sets.

PubMed

Keim, Daniel A; Hao, Ming C; Dayal, Umeshwar; Lyons, Martha

2007-01-01

One of the common problems businesses need to solve is how to use large volumes of sales histories, Web transactions, and other data to understand the behavior of their customers and increase their revenues. Bar charts are widely used for daily analysis, but only show highly aggregated data. Users often need to visualize detailed multidimensional information reflecting the health of their businesses. In this paper, we propose an innovative visualization solution based on the use of value cells within bar charts to represent business metrics. The value of a transaction can be discretized into one or multiple cells: high-value transactions are mapped to multiple value cells, whereas many small-value transactions are combined into one cell. With value-cell bar charts, users can 1) visualize transaction value distributions and correlations, 2) identify high-value transactions and outliers at a glance, and 3) instantly display values at the transaction record level. Value-Cell Bar Charts have been applied with success to different sales and IT service usage applications, demonstrating the benefits of the technique over traditional charting techniques. A comparison with two variants of the well-known Treemap technique and our earlier work on Pixel Bar Charts is also included.

Integration of information and volume visualization for analysis of cell lineage and gene expression during embryogenesis

NASA Astrophysics Data System (ADS)

Cedilnik, Andrej; Baumes, Jeffrey; Ibanez, Luis; Megason, Sean; Wylie, Brian

2008-01-01

Dramatic technological advances in the field of genomics have made it possible to sequence the complete genomes of many different organisms. With this overwhelming amount of data at hand, biologists are now confronted with the challenge of understanding the function of the many different elements of the genome. One of the best places to start gaining insight on the mechanisms by which the genome controls an organism is the study of embryogenesis. There are multiple and inter-related layers of information that must be established in order to understand how the genome controls the formation of an organism. One is cell lineage which describes how patterns of cell division give rise to different parts of an organism. Another is gene expression which describes when and where different genes are turned on. Both of these data types can now be acquired using fluorescent laser-scanning (confocal or 2-photon) microscopy of embryos tagged with fluorescent proteins to generate 3D movies of developing embryos. However, analyzing the wealth of resulting images requires tools capable of interactively visualizing several different types of information as well as being scalable to terabytes of data. This paper describes how the combination of existing large data volume visualization and the new Titan information visualization framework of the Visualization Toolkit (VTK) can be applied to the problem of studying the cell lineage of an organism. In particular, by linking the visualization of spatial and temporal gene expression data with novel ways of visualizing cell lineage data, users can study how the genome regulates different aspects of embryonic development.

Mechanisms of recovery of visual function in adult amblyopia through a tailored action video game.

PubMed

Vedamurthy, Indu; Nahum, Mor; Bavelier, Daphne; Levi, Dennis M

2015-02-26

Amblyopia is a deficit in vision that arises from abnormal visual experience early in life. It was long thought to develop into a permanent deficit, unless properly treated before the end of the sensitive period for visual recovery. However, a number of studies now suggest that adults with long-standing amblyopia may at least partially recover visual acuity and stereopsis following perceptual training. Eliminating or reducing interocular suppression has been hypothesized to be at the root of these changes. Here we show that playing a novel dichoptic video game indeed results in reduced suppression, improved visual acuity and, in some cases, improved stereopsis. Our relatively large cohort of adults with amblyopia, allowed us, for the first time, to assess the link between visual function recovery and reduction in suppression. Surprisingly, no significant correlation was found between decreased suppression and improved visual function. This finding challenges the prevailing view and suggests that while dichoptic training improves visual acuity and stereopsis in adult amblyopia, reduced suppression is unlikely to be at the root of visual recovery. These results are discussed in the context of their implication on recovery of amblyopia in adults.

Mechanisms of recovery of visual function in adult amblyopia through a tailored action video game

PubMed Central

Vedamurthy, Indu; Nahum, Mor; Bavelier, Daphne; Levi, Dennis M.

2015-01-01

Amblyopia is a deficit in vision that arises from abnormal visual experience early in life. It was long thought to develop into a permanent deficit, unless properly treated before the end of the sensitive period for visual recovery. However, a number of studies now suggest that adults with long-standing amblyopia may at least partially recover visual acuity and stereopsis following perceptual training. Eliminating or reducing interocular suppression has been hypothesized to be at the root of these changes. Here we show that playing a novel dichoptic video game indeed results in reduced suppression, improved visual acuity and, in some cases, improved stereopsis. Our relatively large cohort of adults with amblyopia, allowed us, for the first time, to assess the link between visual function recovery and reduction in suppression. Surprisingly, no significant correlation was found between decreased suppression and improved visual function. This finding challenges the prevailing view and suggests that while dichoptic training improves visual acuity and stereopsis in adult amblyopia, reduced suppression is unlikely to be at the root of visual recovery. These results are discussed in the context of their implication on recovery of amblyopia in adults. PMID:25719537

Adaptive Optics Analysis of Visual Benefit with Higher-order Aberrations Correction of Human Eye - Poster Paper

NASA Astrophysics Data System (ADS)

Xue, Lixia; Dai, Yun; Rao, Xuejun; Wang, Cheng; Hu, Yiyun; Liu, Qian; Jiang, Wenhan

2008-01-01

Higher-order aberrations correction can improve visual performance of human eye to some extent. To evaluate how much visual benefit can be obtained with higher-order aberrations correction we developed an adaptive optics vision simulator (AOVS). Dynamic real time optimized modal compensation was used to implement various customized higher-order ocular aberrations correction strategies. The experimental results indicate that higher-order aberrations correction can improve visual performance of human eye comparing with only lower-order aberration correction but the improvement degree and higher-order aberration correction strategy are different from each individual. Some subjects can acquire great visual benefit when higher-order aberrations were corrected but some subjects acquire little visual benefit even though all higher-order aberrations were corrected. Therefore, relative to general lower-order aberrations correction strategy, customized higher-order aberrations correction strategy is needed to obtain optimal visual improvement for each individual. AOVS provides an effective tool for higher-order ocular aberrations optometry for customized ocular aberrations correction.

Estimation of ovular fiber production in cotton

DOEpatents

Van`t Hof, J.

1998-09-01

The present invention is a method for rendering cotton fiber cells that are post-anthesis and pre-harvest available for analysis of their physical properties. The method includes the steps of hydrolyzing cotton fiber cells and separating cotton fiber cells from cotton ovules thereby rendering the cells available for analysis. The analysis of the fiber cells is through any suitable means, e.g., visual inspection. Visual inspection of the cells can be accomplished by placing the cells under an instrument for detection, such as microscope or other means. 4 figs.

Estimation of ovular fiber production in cotton

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

Van`t Hof, J.

The present invention is a method for rendering cotton fiber cells that are post-anthesis and pre-harvest available for analysis of their physical properties. The method includes the steps of hydrolyzing cotton fiber cells and separating cotton fiber cells from cotton ovules thereby rendering the cells available for analysis. The analysis of the fiber cells is through any suitable means, e.g., visual inspection. Visual inspection of the cells can be accomplished by placing the cells under an instrument for detection, such as microscope or other means. 4 figs.

The potential of the second sight system bionic eye implant for partial sight restoration.

PubMed

Luo, Yvonne Hsu-Lin; Fukushige, Eka; Da Cruz, Lyndon

2016-07-01

Second Sight System bionic eye implant, a commercially available visual prosthesis developed by Second Sight Medical Products, has been implanted in over 125 patients with outer retinal dystrophies such as retinitis pigmentosa. The system has gained regulatory approval in both the USA and Europe, and aims to restore vision by electrical stimulation of the nerve cells of the inner retina. In this review, we present the safety profile of this implant from the international clinical trial and discuss the nature and levels of improvement in visual function achieved by patients implanted with the system. Expert commentary: Future developments for the system will be explored following the discussion of the current usefulness of the device, its limitation as and the areas in which further development is necessary.

Intensive video gaming improves encoding speed to visual short-term memory in young male adults.

PubMed

Wilms, Inge L; Petersen, Anders; Vangkilde, Signe

2013-01-01

The purpose of this study was to measure the effect of action video gaming on central elements of visual attention using Bundesen's (1990) Theory of Visual Attention. To examine the cognitive impact of action video gaming, we tested basic functions of visual attention in 42 young male adults. Participants were divided into three groups depending on the amount of time spent playing action video games: non-players (<2h/month, N=12), casual players (4-8h/month, N=10), and experienced players (>15h/month, N=20). All participants were tested in three tasks which tap central functions of visual attention and short-term memory: a test based on the Theory of Visual Attention (TVA), an enumeration test and finally the Attentional Network Test (ANT). The results show that action video gaming does not seem to impact the capacity of visual short-term memory. However, playing action video games does seem to improve the encoding speed of visual information into visual short-term memory and the improvement does seem to depend on the time devoted to gaming. This suggests that intense action video gaming improves basic attentional functioning and that this improvement generalizes into other activities. The implications of these findings for cognitive rehabilitation training are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of the effect of erythropoietin + corticosteroid versus corticosteroid alone in methanol-induced optic nerve neuropathy.

PubMed

Zamani, Nasim; Hassanian-Moghaddam, Hossein; Shojaei, Maziar; Rahimian, Sara

2018-06-01

Following methanol intoxication, optic nerve neuropathy may occur, which is currently treated by different therapeutic regimens. Erythropoietin (EPO) has recently been introduced as a good therapeutic option in methanol-induced optic neuropathy. The aim of the current study was to evaluate the efficacy of EPO in improvement of the visual disturbances in methanol-intoxicated patients. In a case-control study, all patients who had referred to our toxicology centre with confirmed diagnosis of methanol toxicity were considered to be included. Of them, those who had referred with visual disturbances, survived, and their visual disturbances had not improved after haemodialysis were entered. Cases received EPO and corticosteroids while controls only received corticosteroids. They were then compared regarding their visual outcome. All five patients in the control group mentioned that after discharge, their visual acuity had improved while in the cases, three mentioned visual improvement, two mentioned their visual acuity had deteriorated after discharge, two mentioned no change in their visual acuity and three mentioned that their visual acuity had first improved but then deteriorated with a mean two-month interval period. In fundoscopic evaluations, two controls had normal fundospcopy while eight cases had abnormal fundoscopy (p = 0.055). Protective effect of EPO on methanol-induced optic nerve may be strong at the beginning of the intervention but is probably transient.

Mixing of Chromatic and Luminance Retinal Signals in Primate Area V1.

PubMed

Li, Xiaobing; Chen, Yao; Lashgari, Reza; Bereshpolova, Yulia; Swadlow, Harvey A; Lee, Barry B; Alonso, Jose Manuel

2015-07-01

Vision emerges from activation of chromatic and achromatic retinal channels whose interaction in visual cortex is still poorly understood. To investigate this interaction, we recorded neuronal activity from retinal ganglion cells and V1 cortical cells in macaques and measured their visual responses to grating stimuli that had either luminance contrast (luminance grating), chromatic contrast (chromatic grating), or a combination of the two (compound grating). As with parvocellular or koniocellular retinal ganglion cells, some V1 cells responded mostly to the chromatic contrast of the compound grating. As with magnocellular retinal ganglion cells, other V1 cells responded mostly to the luminance contrast and generated a frequency-doubled response to equiluminant chromatic gratings. Unlike magnocellular and parvocellular retinal ganglion cells, V1 cells formed a unimodal distribution for luminance/color preference with a 2- to 4-fold bias toward luminance. V1 cells associated with positive local field potentials in deep layers showed the strongest combined responses to color and luminance and, as a population, V1 cells encoded a diverse combination of luminance/color edges that matched edge distributions of natural scenes. Taken together, these results suggest that the primary visual cortex combines magnocellular and parvocellular retinal inputs to increase cortical receptive field diversity and to optimize visual processing of our natural environment. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Visual function in anterior ischemic optic neuropathy: effect of Vision Restoration Therapy--a pilot study.

PubMed

Jung, Cecilia S; Bruce, Beau; Newman, Nancy J; Biousse, Valérie

2008-05-15

To evaluate the effects of Vision Restoration Therapy (VRT) on the visual function of patients with anterior ischemic optic neuropathy. Randomized controlled double-blind pilot trial. 10 patients with stable anterior ischemic optic neuropathy (AION). All patients were evaluated before VRT and after 3 and 6 months of treatment by Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, contrast sensitivity, reading speed, 24-2 SITA-standard Humphrey visual field (HVF), High Resolution Perimetry (HRP) (perimetry obtained during VRT), and vision-based quality of life questionnaire. Patients were randomized between two VRT strategies (5 in each group): I) VRT in which stimulation was performed in the seeing VF of the affected eye ("seeing field-VRT"); II) VRT in which stimulation was performed along the area of central fixation and in the ARV (areas of residual vision) of the affected eye ("ARV-VRT"). The results of the HRP, HVF, and clinical assessment of visual function were compared for each patient and between the two groups at each evaluation. Visual acuity qualitatively improved in the ARV-VRT group, however the change was not statistically significant (p=0.28). Binocular reading speed significantly improved in the ARV-VRT group (p=0.03). HVF foveal sensitivity increased mildly in both groups (p=0.059). HRP analysis showed a similar increase in stimulus accuracy in both groups (mean improvement of about 15%). All patients reported functional improvement after VRT. Despite a small sample, the study showed a trend toward improvement of visual function in the ARV-VRT group. Improvement of HRP in both groups may reflect diffusely increased visual attention (neuronal activation), or improvement of an underlying sub-clinical abnormality in the "seeing" visual field of patients with optic neuropathies.

Telomere Attrition in Human Lens Epithelial Cells Associated with Oxidative Stress Provide a New Therapeutic Target for the Treatment, Dissolving and Prevention of Cataract with N-Acetylcarnosine Lubricant Eye Drops. Kinetic, Pharmacological and Activity-Dependent Separation of Therapeutic Targeting: Transcorneal Penetration and Delivery of L-Carnosine in the Aqueous Humor and Hormone-Like Hypothalamic Antiaging Effects of the Instilled Ophthalmic Drug Through a Safe Eye Medication Technique.

PubMed

Babizhayev, Mark A; Yegorov, Yegor E

2016-01-01

Visual impairment broadly impacts the ability of affected people to maintain their function and to remain independent during their daily occupations as they grow older. Visual impairment affects survival of older patients, quality of life, can affect a person's self-ranking of health, may be associated with social and functional decline, use of community support services, depression, falls, nursing home placement, and increased mortality. It has been hypothesized that senile cataract may serve as a marker for generalised tissue aging, since structural changes occurring in the proteins of the lens during cataract formation are similar to those which occur elsewhere as part of the aging process. The published analysis revealed a strong age-dependent relationship between undergoing cataract surgery and subsequent mortality. Nuclear opacity, particularly severe nuclear opacity, and mixed opacities with nuclear were significant predictors of mortality independent of body mass index, comorbid conditions, smoking, age, race, and sex. The lens opacity status is considered as an independent predictor of 2-year mortality, an association that could not be explained by potential confounders. Telomeres have become important biomarkers for aging as well as for oxidative stress-related disease. The lens epithelium is especially vulnerable to oxidative stress. Oxidative damage to the cuboidal epithelial cells on the anterior surface of the lens mediated by reactive oxygen species and phospholipid hydroperoxides can precede and contribute to human lens cataract formation. The erosion and shortening of telomeres in human lens epithelial cells in the lack of telomerase activity has been recognized as a primary cause of premature lens senescence phenotype that trigger human cataractogenesis. In this study we aimed to be focused on research defining the mechanisms that underlie linkages among telomere attrition in human lens epithelial cells associated with oxidative stress, biology of the lens response to oxidative damages, aging and health, cataract versus neuroendocrine regulation and disease. The cumulative results demonstrate that carnosine, released ophthalmically from the patented 1% Nacetylcarnosine prodrug lubricant eye drops, at physiological concentration might remarkably reduce the rate of telomere shortening in the lens cells subjected to oxidative stress in the lack of efficient antioxidant lens protection. Carnosine promotes the protection of normal cells from acquiring phenotypic characteristics of cellular senescence. The data of visual functions (visual acuity, glare sensitivity) in older adult subjects and older subjects with cataract treated with 1% N-acetylcarnosine lubricant eye drops showed significant improvement as compared, by contrast with the control group which showed generally no improvement in visual functions, with no difference from baseline in visual acuity and glare sensitivity readings. N-acetylcarnosine derived from the lubricant eye drops may be transported into the hypothalamic tuberomammillary nucleus (TMN) histamine neurons and gradually hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and hormone-like antiaging and anti-cataract physiological function. The research utilizing the N-acetylcarnosine lubricant eye drops powerful therapeutic platform provides the findings related to the intraocular uptake exposure sources as well as a timing dosage and duration systemic absorption of said preparation from the conjunctional sac reaching the hypothalamus with activities transfer into the hypothalamic-neuroendocrine pathways affecting across the hypothalamus metabolic pathway the telomere biology and cataract disease occurrence, reversal and prevention and the average expected lifespan of an individual. Such findings can be translated into clinical practice and may provide a basis for personalized cataract disease and aging prevention and treatment approaches.

Live visualization of genomic loci with BiFC-TALE

PubMed Central

Hu, Huan; Zhang, Hongmin; Wang, Sheng; Ding, Miao; An, Hui; Hou, Yingping; Yang, Xiaojing; Wei, Wensheng; Sun, Yujie; Tang, Chao

2017-01-01

Tracking the dynamics of genomic loci is important for understanding the mechanisms of fundamental intracellular processes. However, fluorescent labeling and imaging of such loci in live cells have been challenging. One of the major reasons is the low signal-to-background ratio (SBR) of images mainly caused by the background fluorescence from diffuse full-length fluorescent proteins (FPs) in the living nucleus, hampering the application of live cell genomic labeling methods. Here, combining bimolecular fluorescence complementation (BiFC) and transcription activator-like effector (TALE) technologies, we developed a novel method for labeling genomic loci (BiFC-TALE), which largely reduces the background fluorescence level. Using BiFC-TALE, we demonstrated a significantly improved SBR by imaging telomeres and centromeres in living cells in comparison with the methods using full-length FP. PMID:28074901

Live visualization of genomic loci with BiFC-TALE.

PubMed

Hu, Huan; Zhang, Hongmin; Wang, Sheng; Ding, Miao; An, Hui; Hou, Yingping; Yang, Xiaojing; Wei, Wensheng; Sun, Yujie; Tang, Chao

2017-01-11

Tracking the dynamics of genomic loci is important for understanding the mechanisms of fundamental intracellular processes. However, fluorescent labeling and imaging of such loci in live cells have been challenging. One of the major reasons is the low signal-to-background ratio (SBR) of images mainly caused by the background fluorescence from diffuse full-length fluorescent proteins (FPs) in the living nucleus, hampering the application of live cell genomic labeling methods. Here, combining bimolecular fluorescence complementation (BiFC) and transcription activator-like effector (TALE) technologies, we developed a novel method for labeling genomic loci (BiFC-TALE), which largely reduces the background fluorescence level. Using BiFC-TALE, we demonstrated a significantly improved SBR by imaging telomeres and centromeres in living cells in comparison with the methods using full-length FP.

Visualizing without Vision at the Microscale: Students with Visual Impairments Explore Cells with Touch

ERIC Educational Resources Information Center

Jones, M. Gail; Minogue, James; Oppewal, Tom; Cook, Michelle P.; Broadwell, Bethany

2006-01-01

Science instruction is typically highly dependent on visual representations of scientific concepts that are communicated through textbooks, teacher presentations, and computer-based multimedia materials. Little is known about how students with visual impairments access and interpret these types of visually-dependent instructional materials. This…

Increased internal higher-order aberrations as a useful parameter for indication of vitrectomy in three asteroid hyalosis cases

PubMed Central

Yokoyama, Sho; Kojima, Takashi; Kaga, Tatsushi; Ichikawa, Kazuo

2015-01-01

We report three asteroid hyalosis cases in which internal higher-order aberrations (HOAs) were improved concomitant with improved visual symptoms after vitrectomy. Cases 1 and 2 reported severe floaters and glare disability, although their visual acuities were fairly good. Case 3 showed poor visual acuity since this patient also suffered from mild macular degeneration. For these three asteroid hyalosis cases, we were unsure if treatment with vitrectomy could improve visual symptoms. Therefore, we measured internal HOAs with an aberrometer, and found that the internal HOA values in these cases were high. We suspected that internal high HOAs values were associated with visual disturbance, and performed vitrectomy. After the vitrectomy, the internal HOA values in these three asteroid hyalosis cases markedly decreased, and visual symptoms improved. These observations suggested that measurement of internal HOAs may be useful to determine the indication for vitrectomy. PMID:26698200

Increased internal higher-order aberrations as a useful parameter for indication of vitrectomy in three asteroid hyalosis cases.

PubMed

Yokoyama, Sho; Kojima, Takashi; Kaga, Tatsushi; Ichikawa, Kazuo

2015-12-23

We report three asteroid hyalosis cases in which internal higher-order aberrations (HOAs) were improved concomitant with improved visual symptoms after vitrectomy. Cases 1 and 2 reported severe floaters and glare disability, although their visual acuities were fairly good. Case 3 showed poor visual acuity since this patient also suffered from mild macular degeneration. For these three asteroid hyalosis cases, we were unsure if treatment with vitrectomy could improve visual symptoms. Therefore, we measured internal HOAs with an aberrometer, and found that the internal HOA values in these cases were high. We suspected that internal high HOAs values were associated with visual disturbance, and performed vitrectomy. After the vitrectomy, the internal HOA values in these three asteroid hyalosis cases markedly decreased, and visual symptoms improved. These observations suggested that measurement of internal HOAs may be useful to determine the indication for vitrectomy. 2015 BMJ Publishing Group Ltd.

A randomized controlled trial comparing 2 interventions for visual field loss with standard occupational therapy during inpatient stroke rehabilitation.

PubMed

Mödden, Claudia; Behrens, Marion; Damke, Iris; Eilers, Norbert; Kastrup, Andreas; Hildebrandt, Helmut

2012-06-01

Compensatory and restorative treatments have been developed to improve visual field defects after stroke. However, no controlled trials have compared these interventions with standard occupational therapy (OT). A total of 45 stroke participants with visual field defect admitted for inpatient rehabilitation were randomized to restorative computerized training (RT) using computer-based stimulation of border areas of their visual field defects or to a computer-based compensatory therapy (CT) teaching a visual search strategy. OT, in which different compensation strategies were used to train for activities of daily living, served as standard treatment for the active control group. Each treatment group received 15 single sessions of 30 minutes distributed over 3 weeks. The primary outcome measures were visual field expansion for RT, visual search performance for CT, and reading performance for both treatments. Visual conjunction search, alertness, and the Barthel Index were secondary outcomes. Compared with OT, CT resulted in a better visual search performance, and RT did not result in a larger expansion of the visual field. Intragroup pre-post comparisons demonstrated that CT improved all defined outcome parameters and RT several, whereas OT only improved one. CT improved functional deficits after visual field loss compared with standard OT and may be the intervention of choice during inpatient rehabilitation. A larger trial that includes lesion location in the analysis is recommended.

Audio-visual speech intelligibility benefits with bilateral cochlear implants when talker location varies.

PubMed

van Hoesel, Richard J M

2015-04-01

One of the key benefits of using cochlear implants (CIs) in both ears rather than just one is improved localization. It is likely that in complex listening scenes, improved localization allows bilateral CI users to orient toward talkers to improve signal-to-noise ratios and gain access to visual cues, but to date, that conjecture has not been tested. To obtain an objective measure of that benefit, seven bilateral CI users were assessed for both auditory-only and audio-visual speech intelligibility in noise using a novel dynamic spatial audio-visual test paradigm. For each trial conducted in spatially distributed noise, first, an auditory-only cueing phrase that was spoken by one of four talkers was selected and presented from one of four locations. Shortly afterward, a target sentence was presented that was either audio-visual or, in another test configuration, audio-only and was spoken by the same talker and from the same location as the cueing phrase. During the target presentation, visual distractors were added at other spatial locations. Results showed that in terms of speech reception thresholds (SRTs), the average improvement for bilateral listening over the better performing ear alone was 9 dB for the audio-visual mode, and 3 dB for audition-alone. Comparison of bilateral performance for audio-visual and audition-alone showed that inclusion of visual cues led to an average SRT improvement of 5 dB. For unilateral device use, no such benefit arose, presumably due to the greatly reduced ability to localize the target talker to acquire visual information. The bilateral CI speech intelligibility advantage over the better ear in the present study is much larger than that previously reported for static talker locations and indicates greater everyday speech benefits and improved cost-benefit than estimated to date.

Improvement of visual acuity by refraction in a low-vision population.

PubMed

Sunness, Janet S; El Annan, Jaafar

2010-07-01

Refraction often may be overlooked in low-vision patients, because the main cause of vision decrease is not refractive, but rather is the result of underlying ocular disease. This retrospective study was carried out to determine how frequently and to what extent visual acuity is improved by refraction in a low-vision population. Cross-sectional study. Seven hundred thirty-nine low-vision patients seen for the first time. A database with all new low-vision patients seen from November 2005 through June 2008 recorded presenting visual acuity using an Early Treatment Diabetic Retinopathy Study chart; it also recorded the best-corrected visual acuity (BCVA) if it was 2 lines or more better than the presenting visual acuity. Retinoscopy was carried out on all patients, followed by manifest refraction. Improvement in visual acuity. Median presenting acuity was 20/80(-2) (interquartile range, 20/50-20/200). There was an improvement of 2 lines or more of visual acuity in 81 patients (11% of all patients), with 22 patients (3% of all patients) improving by 4 lines or more. There was no significant difference in age or in presenting visual acuity between the group that did not improve by refraction and the group that did improve. When stratified by diagnosis, the only 2 diagnoses with a significantly higher rate of improvement than the age-related macular degeneration group were myopic degeneration and progressive myopia (odds ratio, 4.8; 95% confidence interval [CI], 3.0-6.7) and status post-retinal detachment (odds ratio, 7.1; 95% CI, 5.2-9.0). For 5 patients (6% of those with improvement), the eye that was 1 line or more worse than the fellow eye at presentation became the eye that was 1 line or more better than the fellow eye after refraction. A significant improvement in visual acuity was attained by refraction in 11% of the new low-vision patients. Improvement was seen across diagnoses and the range of presenting visual acuity. The worse-seeing eye at presentation may become the better-seeing eye after refraction, so that the eye behind a balance lens should be refracted as well. Proprietary or commercial disclosure may be found after the references. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells

PubMed Central

Miraucourt, Loïs S; Tsui, Jennifer; Gobert, Delphine; Desjardins, Jean-François; Schohl, Anne; Sild, Mari; Spratt, Perry; Castonguay, Annie; De Koninck, Yves; Marsh-Armstrong, Nicholas; Wiseman, Paul W; Ruthazer, Edward S

2016-01-01

Type 1 cannabinoid receptors (CB1Rs) are widely expressed in the vertebrate retina, but the role of endocannabinoids in vision is not fully understood. Here, we identified a novel mechanism underlying a CB1R-mediated increase in retinal ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent inhibition of NKCC1 activity. Clomeleon imaging and patch clamp recordings revealed that inhibition of NKCC1 downstream of CB1R activation reduces intracellular Cl− levels in RGCs, hyperpolarizing the resting membrane potential. We confirmed that such hyperpolarization enhances RGC action potential firing in response to subsequent depolarization, consistent with the increased intrinsic excitability of RGCs observed with CB1R activation. Using a dot avoidance assay in freely swimming Xenopus tadpoles, we demonstrate that CB1R activation markedly improves visual contrast sensitivity under low-light conditions. These results highlight a role for endocannabinoids in vision and present a novel mechanism for cannabinoid modulation of neuronal activity through Cl− regulation. DOI: http://dx.doi.org/10.7554/eLife.15932.001 PMID:27501334

Cells from icons to symbols: molecularizing cell biology in the 1980s.

PubMed

Serpente, Norberto

2011-12-01

Over centuries cells have been the target of optical and electronic microscopes as well as others technologies, with distinctive types of visual output. Whilst optical technologies produce images 'evident to the eye', the electronic and especially the molecular create images that are more elusive to conceptualization and assessment. My study applies the semiotic approach to the production of images in cell biology to capture the shift from microscopic images to non-traditional visual technologies around 1980. Here I argue that the visual shift that coincides with the growing dominance of molecular biology involves a change from iconic to symbolic forms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Public health nurse perceptions of Omaha System data visualization.

PubMed

Lee, Seonah; Kim, Era; Monsen, Karen A

2015-10-01

Electronic health records (EHRs) provide many benefits related to the storage, deployment, and retrieval of large amounts of patient data. However, EHRs have not fully met the need to reuse data for decision making on follow-up care plans. Visualization offers new ways to present health data, especially in EHRs. Well-designed data visualization allows clinicians to communicate information efficiently and effectively, contributing to improved interpretation of clinical data and better patient care monitoring and decision making. Public health nurse (PHN) perceptions of Omaha System data visualization prototypes for use in EHRs have not been evaluated. To visualize PHN-generated Omaha System data and assess PHN perceptions regarding the visual validity, helpfulness, usefulness, and importance of the visualizations, including interactive functionality. Time-oriented visualization for problems and outcomes and Matrix visualization for problems and interventions were developed using PHN-generated Omaha System data to help PHNs consume data and plan care at the point of care. Eleven PHNs evaluated prototype visualizations. Overall PHNs response to visualizations was positive, and feedback for improvement was provided. This study demonstrated the potential for using visualization techniques within EHRs to summarize Omaha System patient data for clinicians. Further research is needed to improve and refine these visualizations and assess the potential to incorporate visualizations within clinical EHRs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Improving Readability of an Evaluation Tool for Low-Income Clients Using Visual Information Processing Theories

ERIC Educational Resources Information Center

Townsend, Marilyn S.; Sylva, Kathryn; Martin, Anna; Metz, Diane; Wooten-Swanson, Patti

2008-01-01

Literacy is an issue for many low-income audiences. Using visual information processing theories, the goal was improving readability of a food behavior checklist and ultimately improving its ability to accurately capture existing changes in dietary behaviors. Using group interviews, low-income clients (n = 18) evaluated 4 visual styles. The text…

Mesenchymal Stem Cells and Their Conditioned Medium Improve Integration of Purified Induced Pluripotent Stem Cell–Derived Cardiomyocyte Clusters into Myocardial Tissue

PubMed Central

Rubach, Martin; Adelmann, Roland; Haustein, Moritz; Drey, Florian; Pfannkuche, Kurt; Xiao, Bing; Koester, Annette; Udink ten Cate, Floris E.A.; Choi, Yeong-Hoon; Neef, Klaus; Fatima, Azra; Hannes, Tobias; Pillekamp, Frank; Hescheler, Juergen; Šarić, Tomo; Brockmeier, Konrad

2014-01-01

Induced pluripotent stem cell–derived cardiomyocytes (iPS-CMs) might become therapeutically relevant to regenerate myocardial damage. Purified iPS-CMs exhibit poor functional integration into myocardial tissue. The aim of this study was to investigate whether murine mesenchymal stem cells (MSCs) or their conditioned medium (MScond) improves the integration of murine iPS-CMs into myocardial tissue. Vital or nonvital embryonic murine ventricular tissue slices were cocultured with purified clusters of iPS-CMs in combination with murine embryonic fibroblasts (MEFs), MSCs, or MScond. Morphological integration was assessed by visual scoring and functional integration by isometric force and field potential measurements. We observed a moderate morphological integration of iPS-CM clusters into vital, but a poor integration into nonvital, slices. MEFs and MSCs but not MScond improved morphological integration of CMs into nonvital slices and enabled purified iPS-CMs to confer force. Coculture of vital slices with iPS-CMs and MEFs or MSCs resulted in an improved electrical integration. A comparable improvement of electrical coupling was achieved with the cell-free MScond, indicating that soluble factors secreted by MSCs were involved in electrical coupling. We conclude that cells such as MSCs support the engraftment and adhesion of CMs, and confer force to noncontractile tissue. Furthermore, soluble factors secreted by MSCs mediate electrical coupling of purified iPS-CM clusters to myocardial tissue. These data suggest that MSCs may increase the functional engraftment and therapeutic efficacy of transplanted iPS-CMs into infarcted myocardium. PMID:24219308

Visual discrimination training improves Humphrey perimetry in chronic cortically induced blindness.

PubMed

Cavanaugh, Matthew R; Huxlin, Krystel R

2017-05-09

To assess if visual discrimination training improves performance on visual perimetry tests in chronic stroke patients with visual cortex involvement. 24-2 and 10-2 Humphrey visual fields were analyzed for 17 chronic cortically blind stroke patients prior to and following visual discrimination training, as well as in 5 untrained, cortically blind controls. Trained patients practiced direction discrimination, orientation discrimination, or both, at nonoverlapping, blind field locations. All pretraining and posttraining discrimination performance and Humphrey fields were collected with online eye tracking, ensuring gaze-contingent stimulus presentation. Trained patients recovered ∼108 degrees 2 of vision on average, while untrained patients spontaneously improved over an area of ∼16 degrees 2 . Improvement was not affected by patient age, time since lesion, size of initial deficit, or training type, but was proportional to the amount of training performed. Untrained patients counterbalanced their improvements with worsening of sensitivity over ∼9 degrees 2 of their visual field. Worsening was minimal in trained patients. Finally, although discrimination performance improved at all trained locations, changes in Humphrey sensitivity occurred both within trained regions and beyond, extending over a larger area along the blind field border. In adults with chronic cortical visual impairment, the blind field border appears to have enhanced plastic potential, which can be recruited by gaze-controlled visual discrimination training to expand the visible field. Our findings underscore a critical need for future studies to measure the effects of vision restoration approaches on perimetry in larger cohorts of patients. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Standard-Fractionated Radiotherapy for Optic Nerve Sheath Meningioma: Visual Outcome Is Predicted by Mean Eye Dose

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

Abouaf, Lucie; Girard, Nicolas; Claude Bernard University, Lyon

2012-03-01

Purpose: Radiotherapy has shown its efficacy in controlling optic nerve sheath meningiomas (ONSM) tumor growth while allowing visual acuity to improve or stabilize. However, radiation-induced toxicity may ultimately jeopardize the functional benefit. The purpose of this study was to identify predictive factors of poor visual outcome in patients receiving radiotherapy for ONSM. Methods and Materials: We conducted an extensive analysis of 10 patients with ONSM with regard to clinical, radiologic, and dosimetric aspects. All patients were treated with conformal radiotherapy and subsequently underwent biannual neuroophthalmologic and imaging assessments. Pretreatment and posttreatment values of visual acuity and visual field were comparedmore » with Wilcoxon's signed rank test. Results: Visual acuity values significantly improved after radiotherapy. After a median follow-up time of 51 months, 6 patients had improved visual acuity, 4 patients had improved visual field, 1 patient was in stable condition, and 1 patient had deteriorated visual acuity and visual field. Tumor control rate was 100% at magnetic resonance imaging assessment. Visual acuity deterioration after radiotherapy was related to radiation-induced retinopathy in 2 patients and radiation-induced mature cataract in 1 patient. Study of radiotherapy parameters showed that the mean eye dose was significantly higher in those 3 patients who had deteriorated vision. Conclusions: Our study confirms that radiotherapy is efficient in treating ONSM. Long-term visual outcome may be compromised by radiation-induced side effects. Mean eye dose has to be considered as a limiting constraint in treatment planning.« less

A method for improved visual landscape compatibility of mobile home park

Treesearch

Daniel R. Jones

1979-01-01

This paper is a description of a research effort directed to improving the visual image of mobile home parks in the landscape. The study is an application of existing methodologies for measuring scenic quality and visual landscape compatibility to an unsolved problem. The paper summarizes two major areas of investigation: regional location factors based on visual...

DspaceOgre 3D Graphics Visualization Tool

NASA Technical Reports Server (NTRS)

Jain, Abhinandan; Myin, Steven; Pomerantz, Marc I.

2011-01-01

This general-purpose 3D graphics visualization C++ tool is designed for visualization of simulation and analysis data for articulated mechanisms. Examples of such systems are vehicles, robotic arms, biomechanics models, and biomolecular structures. DspaceOgre builds upon the open-source Ogre3D graphics visualization library. It provides additional classes to support the management of complex scenes involving multiple viewpoints and different scene groups, and can be used as a remote graphics server. This software provides improved support for adding programs at the graphics processing unit (GPU) level for improved performance. It also improves upon the messaging interface it exposes for use as a visualization server.

The Effect of Autologous Platelet Lysate Eye Drops: An In Vivo Confocal Microscopy Study

PubMed Central

Fea, Antonio M.; Testa, Valeria; Machetta, Federica; Parisi, Simone; D'Antico, Sergio; Spinetta, Roberta; Fusaro, Enrico; Grignolo, Federico M.

2016-01-01

Purpose. To determine the effectiveness of autologous platelet lysate (APL) eye drops in patients with primary Sjögren syndrome (SS) dry eye, refractory to standard therapy, in comparison with patients treated with artificial tears. We focused on the effect of APL on cornea morphology with the in vivo confocal microscopy (IVCM). Methods. Patients were assigned to two groups: group A used autologous platelet lysate QID, and group B used preservative-free artificial tears QID, for 90 days. Ophthalmological assessments included ocular surface disease index (OSDI), best corrected visual acuity (BCVA), Schirmer test, fluorescein score, and breakup time (BUT). A subgroup of patients in group A underwent IVCM: corneal basal epithelium, subbasal nerves, Langerhans cells, anterior stroma activated keratocytes, and reflectivity were evaluated. Results. 60 eyes of 30 patients were enrolled; in group A (n = 20 patients) mean OSDI, fluorescein score, and BUT showed significant improvement compared with group B (n = 10 patients). The IVCM showed a significant increase in basal epithelium cells density and subbasal nerve plexus density and number and a decrease in Langerhans cells density (p < 0.05). Conclusion. APL was found effective in the treatment of SS dry eye. IVCM seems to be a useful tool to visualize cornea morphologic modifications. PMID:27200376

The Effect of Autologous Platelet Lysate Eye Drops: An In Vivo Confocal Microscopy Study.

PubMed

Fea, Antonio M; Aragno, Vittoria; Testa, Valeria; Machetta, Federica; Parisi, Simone; D'Antico, Sergio; Spinetta, Roberta; Fusaro, Enrico; Grignolo, Federico M

2016-01-01

Purpose. To determine the effectiveness of autologous platelet lysate (APL) eye drops in patients with primary Sjögren syndrome (SS) dry eye, refractory to standard therapy, in comparison with patients treated with artificial tears. We focused on the effect of APL on cornea morphology with the in vivo confocal microscopy (IVCM). Methods. Patients were assigned to two groups: group A used autologous platelet lysate QID, and group B used preservative-free artificial tears QID, for 90 days. Ophthalmological assessments included ocular surface disease index (OSDI), best corrected visual acuity (BCVA), Schirmer test, fluorescein score, and breakup time (BUT). A subgroup of patients in group A underwent IVCM: corneal basal epithelium, subbasal nerves, Langerhans cells, anterior stroma activated keratocytes, and reflectivity were evaluated. Results. 60 eyes of 30 patients were enrolled; in group A (n = 20 patients) mean OSDI, fluorescein score, and BUT showed significant improvement compared with group B (n = 10 patients). The IVCM showed a significant increase in basal epithelium cells density and subbasal nerve plexus density and number and a decrease in Langerhans cells density (p < 0.05). Conclusion. APL was found effective in the treatment of SS dry eye. IVCM seems to be a useful tool to visualize cornea morphologic modifications.

A comprehensive statistical classifier of foci in the cell transformation assay for carcinogenicity testing.

PubMed

Callegaro, Giulia; Malkoc, Kasja; Corvi, Raffaella; Urani, Chiara; Stefanini, Federico M

2017-12-01

The identification of the carcinogenic risk of chemicals is currently mainly based on animal studies. The in vitro Cell Transformation Assays (CTAs) are a promising alternative to be considered in an integrated approach. CTAs measure the induction of foci of transformed cells. CTAs model key stages of the in vivo neoplastic process and are able to detect both genotoxic and some non-genotoxic compounds, being the only in vitro method able to deal with the latter. Despite their favorable features, CTAs can be further improved, especially reducing the possible subjectivity arising from the last phase of the protocol, namely visual scoring of foci using coded morphological features. By taking advantage of digital image analysis, the aim of our work is to translate morphological features into statistical descriptors of foci images, and to use them to mimic the classification performances of the visual scorer to discriminate between transformed and non-transformed foci. Here we present a classifier based on five descriptors trained on a dataset of 1364 foci, obtained with different compounds and concentrations. Our classifier showed accuracy, sensitivity and specificity equal to 0.77 and an area under the curve (AUC) of 0.84. The presented classifier outperforms a previously published model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Macular Ganglion Cell Imaging Study: Covariate Effects on the Spectral Domain Optical Coherence Tomography for Glaucoma Diagnosis

PubMed Central

Jeong, Jae Hoon; Choi, Yun Jeong; Park, Ki Ho; Kim, Dong Myung

2016-01-01

Purpose To evaluate the effect of multiple covariates on the diagnostic performance of the Cirrus high-definition optical coherence tomography (HD-OCT) for glaucoma detection. Methods A prospective case-control study was performed and included 173 recently diagnosed glaucoma patients and 63 unaffected individuals from the Macular Ganglion Cell Imaging Study. Regression analysis of receiver operating characteristic were conducted to evaluate the influence of age, spherical equivalent, axial length, optic disc size, and visual field index on the macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) measurements. Results Disease severity, as measured by visual field index, had a significant effect on the diagnostic performance of all Cirrus HD-OCT parameters. Age, axial length and optic disc size were significantly associated with diagnostic accuracy of average peripapillary RNFL thickness, whereas axial length had a significant effect on the diagnostic accuracy of average GCIPL thickness. Conclusions Diagnostic performance of the Cirrus HD-OCT may be more accurate in the advanced stages of glaucoma than at earlier stages. A smaller optic disc size was significantly associated with improved the diagnostic ability of average RNFL thickness measurements; however, GCIPL thickness may be less affected by age and optic disc size. PMID:27490718

Live imaging of apoptotic cells in zebrafish

PubMed Central

van Ham, Tjakko J.; Mapes, James; Kokel, David; Peterson, Randall T.

2010-01-01

Many debilitating diseases, including neurodegenerative diseases, involve apoptosis. Several methods have been developed for visualizing apoptotic cells in vitro or in fixed tissues, but few tools are available for visualizing apoptotic cells in live animals. Here we describe a genetically encoded fluorescent reporter protein that labels apoptotic cells in live zebrafish embryos. During apoptosis, the phospholipid phosphatidylserine (PS) is exposed on the outer leaflet of the plasma membrane. The calcium-dependent protein Annexin V (A5) binds PS with high affinity, and biochemically purified, fluorescently labeled A5 probes have been widely used to detect apoptosis in vitro. Here we show that secreted A5 fused to yellow fluorescent protein specifically labels apoptotic cells in living zebrafish. We use this fluorescent probe to characterize patterns of apoptosis in living zebrafish larvae and to visualize neuronal cell death at single-cell resolution in vivo.—Van Ham, T. J., Mapes, J., Kokel, D., Peterson, R. T. Live imaging of apoptotic cells in zebrafish. PMID:20601526

Live-cell visualization of gasdermin D-driven pyroptotic cell death.

PubMed

Rathkey, Joseph K; Benson, Bryan L; Chirieleison, Steven M; Yang, Jie; Xiao, Tsan S; Dubyak, George R; Huang, Alex Y; Abbott, Derek W

2017-09-01

Pyroptosis is a form of cell death important in defenses against pathogens that can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, GSDMD (gasdermin D), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has complicated our ability to understand the biology of this protein. Studies aimed at visualizing GSDMD have relied on expression of GSDMD fragments in epithelial cell lines that naturally lack GSDMD expression and also lack the proteases necessary to cleave GSDMD. In this work, we performed mutagenesis and molecular modeling to strategically place tags and fluorescent proteins within GSDMD that support native pyroptosis and facilitate live-cell imaging of pyroptotic cell death. Here, we demonstrate that these fusion proteins are cleaved by caspases-1 and -11 at Asp-276. Mutations that disrupted the predicted p30-p20 autoinhibitory interface resulted in GSDMD aggregation, supporting the oligomerizing activity of these mutations. Furthermore, we show that these novel GSDMD fusions execute inflammasome-dependent pyroptotic cell death in response to multiple stimuli and allow for visualization of the morphological changes associated with pyroptotic cell death in real time. This work therefore provides new tools that not only expand the molecular understanding of pyroptosis but also enable its direct visualization. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Vision's Brain.

ERIC Educational Resources Information Center

Miller, Julie Ann

1978-01-01

The functional architecture of the primary visual cortex has been explored by monitoring the responses of individual brain cells to visual stimuli. A combination of anatomical and physiological techniques reveals groups of functionally related cells, juxtaposed and superimposed, in a sometimes complex, but presumably efficient, structure. (BB)

Visualization of MMP-2 Activity Using Dual-Probe Nanoparticles to Detect Potential Metastatic Cancer Cells

PubMed Central

Kim, Sung Hoon; Lee, Hyun; Kim, Bohee; Kim, Yoon Suk; Key, Jaehong

2018-01-01

Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes capable of degrading extracellular matrix components. Previous studies have shown that the upregulation of MMP-2 is closely related to metastatic cancers. While Western blotting, zymography, and Enzyme-Linked Immunosorbent Assays (ELISA) can be used to measure the amount of MMP-2 activity, it is not possible to visualize the dynamic MMP-2 activities of cancer cells using these techniques. In this study, MMP-2-activated poly(lactic-co-glycolic acid) with polyethylenimine (MMP-2-PLGA-PEI) nanoparticles were developed to visualize time-dependent MMP-2 activities. The MMP-2-PLGA-PEI nanoparticles contain MMP-2-activated probes that were detectable via fluorescence microscopy only in the presence of MMP-2 activity, while the Rhodamine-based probes in the nanoparticles were used to continuously visualize the location of the nanoparticles. This approach allowed us to visualize MMP-2 activities in cancer cells and their microenvironment. Our results showed that the MMP-2-PLGA-PEI nanoparticles were able to distinguish between MMP-2-positive (HaCat) and MMP-2-negative (MCF-7) cells. While the MMP-2-PLGA-PEI nanoparticles gave fluorescent signals recovered by active recombinant MMP-2, there was no signal recovery in the presence of an MMP-2 inhibitor. In conclusion, MMP-2-PLGA-PEI nanoparticles are an effective tool to visualize dynamic MMP-2 activities of potential metastatic cancer cells. PMID:29466303

Liquid Water Saturation and Oxygen Transport Resistance in Polymer Electrolyte Membrane Fuel Cell Gas Diffusion Layers

NASA Astrophysics Data System (ADS)

Muirhead, Daniel

In this thesis, the relative humidity (RH) of the cathode reactant gas was investigated as a factor which influences gas diffusion layer (GDL) liquid water accumulation and mass transport-related efficiency losses over a range of operating current densities in a polymer electrolyte membrane (PEM) fuel cell. Limiting current measurements were used to characterize fuel cell oxygen transport resistance while simultaneous measurements of liquid water accumulation were conducted using synchrotron X-ray radiography. GDL porosity distributions were characterized with micro-computed tomography (microCT). The work presented here can be used by researchers to develop improved numerical models to predict GDL liquid water accumulation and to inform the design of next-generation GDL materials to mitigate mass transport-related efficiency losses. This work also contributes an extensive set of concurrent performance and liquid water visualization data to the PEM fuel cell field that can be used for validating multiphase transport models.

A cooperation and competition based simple cell receptive field model and study of feed-forward linear and nonlinear contributions to orientation selectivity.

PubMed

Bhaumik, Basabi; Mathur, Mona

2003-01-01

We present a model for development of orientation selectivity in layer IV simple cells. Receptive field (RF) development in the model, is determined by diffusive cooperation and resource limited competition guided axonal growth and retraction in geniculocortical pathway. The simulated cortical RFs resemble experimental RFs. The receptive field model is incorporated in a three-layer visual pathway model consisting of retina, LGN and cortex. We have studied the effect of activity dependent synaptic scaling on orientation tuning of cortical cells. The mean value of hwhh (half width at half the height of maximum response) in simulated cortical cells is 58 degrees when we consider only the linear excitatory contribution from LGN. We observe a mean improvement of 22.8 degrees in tuning response due to the non-linear spiking mechanisms that include effects of threshold voltage and synaptic scaling factor.

Visual and Motor Recovery After "Cognitive Therapeutic Exercises" in Cortical Blindness: A Case Study.

PubMed

De Patre, Daniele; Van de Winckel, Ann; Panté, Franca; Rizzello, Carla; Zernitz, Marina; Mansour, Mariam; Zordan, Lara; Zeffiro, Thomas A; OʼConnor, Erin E; Bisson, Teresa; Lupi, Andrea; Perfetti, Carlo

2017-07-01

Spontaneous visual recovery is rare after cortical blindness. While visual rehabilitation may improve performance, no visual therapy has been widely adopted, as clinical outcomes are variable and rarely translate into improvements in activities of daily living (ADLs). We explored the potential value of a novel rehabilitation approach "cognitive therapeutic exercises" for cortical blindness. The subject of this case study was 48-year-old woman with cortical blindness and tetraplegia after cardiac arrest. Prior to the intervention, she was dependent in ADLs and poorly distinguished shapes and colors after 19 months of standard visual and motor rehabilitation. Computed tomographic images soon after symptom onset demonstrated acute infarcts in both occipital cortices. The subject underwent 8 months of intensive rehabilitation with "cognitive therapeutic exercises" consisting of discrimination exercises correlating sensory and visual information. Visual fields increased; object recognition improved; it became possible to watch television; voluntary arm movements improved in accuracy and smoothness; walking improved; and ADL independence and self-reliance increased. Subtraction of neuroimaging acquired before and after rehabilitation showed that focal glucose metabolism increases bilaterally in the occipital poles. This study demonstrates feasibility of "cognitive therapeutic exercises" in an individual with cortical blindness, who experienced impressive visual and sensorimotor recovery, with marked ADL improvement, more than 2 years after ischemic cortical damage.Video Abstract available for additional insights from the authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A173).

In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells.

PubMed

Jung, Kwang Bo; Lee, Hana; Son, Ye Seul; Lee, Ji Hye; Cho, Hyun-Soo; Lee, Mi-Ok; Oh, Jung-Hwa; Lee, Jaemin; Kim, Seokho; Jung, Cho-Rok; Kim, Janghwan; Son, Mi-Young

2018-01-01

Human intestinal organoids (hIOs) derived from human pluripotent stem cells (hPSCs) have immense potential as a source of intestines. Therefore, an efficient system is needed for visualizing the stage of intestinal differentiation and further identifying hIOs derived from hPSCs. Here, 2 fluorescent biosensors were developed based on human induced pluripotent stem cell (hiPSC) lines that stably expressed fluorescent reporters driven by intestine-specific gene promoters Krüppel-like factor 5 monomeric Cherry (KLF5 mCherry ) and intestine-specific homeobox enhanced green fluorescence protein (ISX eGFP ). Then hIOs were efficiently induced from those transgenic hiPSC lines in which mCherry- or eGFP-expressing cells, which appeared during differentiation, could be identified in intact living cells in real time. Reporter gene expression had no adverse effects on differentiation into hIOs and proliferation. Using our reporter system to screen for hIO differentiation factors, we identified DMH1 as an efficient substitute for Noggin. Transplanted hIOs under the kidney capsule were tracked with fluorescence imaging (FLI) and confirmed histologically. After orthotopic transplantation, the localization of the hIOs in the small intestine could be accurately visualized using FLI. Our study establishes a selective system for monitoring the in vitro differentiation and for tracking the in vivo localization of hIOs and contributes to further improvement of cell-based therapies and preclinical screenings in the intestinal field.-Jung, K. B., Lee, H., Son, Y. S., Lee, J. H., Cho, H.-S., Lee, M.-O., Oh, J.-H., Lee, J., Kim, S., Jung, C.-R., Kim, J., Son, M.-Y. In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells. © FASEB.

Retinal ganglion cell maps in the brain: implications for visual processing.

PubMed

Dhande, Onkar S; Huberman, Andrew D

2014-02-01

Everything the brain knows about the content of the visual world is built from the spiking activity of retinal ganglion cells (RGCs). As the output neurons of the eye, RGCs include ∼20 different subtypes, each responding best to a specific feature in the visual scene. Here we discuss recent advances in identifying where different RGC subtypes route visual information in the brain, including which targets they connect to and how their organization within those targets influences visual processing. We also highlight examples where causal links have been established between specific RGC subtypes, their maps of central connections and defined aspects of light-mediated behavior and we suggest the use of techniques that stand to extend these sorts of analyses to circuits underlying visual perception. Copyright © 2013. Published by Elsevier Ltd.

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

Synchronous activity in cat visual cortex encodes collinear and cocircular contours.

PubMed

Samonds, Jason M; Zhou, Zhiyi; Bernard, Melanie R; Bonds, A B

2006-04-01

We explored how contour information in primary visual cortex might be embedded in the simultaneous activity of multiple cells recorded with a 100-electrode array. Synchronous activity in cat visual cortex was more selective and predictable in discriminating between drifting grating and concentric ring stimuli than changes in firing rate. Synchrony was found even between cells with wholly different orientation preferences when their receptive fields were circularly aligned, and membership in synchronous groups was orientation and curvature dependent. The existence of synchrony between cocircular cells reinforces its role as a general mechanism for contour integration and shape detection as predicted by association field concepts. Our data suggest that cortical synchrony results from common and synchronous input from earlier visual areas and that it could serve to shape extrastriate response selectivity.

Audio-Visual Situational Awareness for General Aviation Pilots

NASA Technical Reports Server (NTRS)

Spirkovska, Lilly; Lodha, Suresh K.; Clancy, Daniel (Technical Monitor)

2001-01-01

Weather is one of the major causes of general aviation accidents. Researchers are addressing this problem from various perspectives including improving meteorological forecasting techniques, collecting additional weather data automatically via on-board sensors and "flight" modems, and improving weather data dissemination and presentation. We approach the problem from the improved presentation perspective and propose weather visualization and interaction methods tailored for general aviation pilots. Our system, Aviation Weather Data Visualization Environment (AWE), utilizes information visualization techniques, a direct manipulation graphical interface, and a speech-based interface to improve a pilot's situational awareness of relevant weather data. The system design is based on a user study and feedback from pilots.

Improving Dorsal Stream Function in Dyslexics by Training Figure/Ground Motion Discrimination Improves Attention, Reading Fluency, and Working Memory.

PubMed

Lawton, Teri

2016-01-01

There is an ongoing debate about whether the cause of dyslexia is based on linguistic, auditory, or visual timing deficits. To investigate this issue three interventions were compared in 58 dyslexics in second grade (7 years on average), two targeting the temporal dynamics (timing) of either the auditory or visual pathways with a third reading intervention (control group) targeting linguistic word building. Visual pathway training in dyslexics to improve direction-discrimination of moving test patterns relative to a stationary background (figure/ground discrimination) significantly improved attention, reading fluency, both speed and comprehension, phonological processing, and both auditory and visual working memory relative to controls, whereas auditory training to improve phonological processing did not improve these academic skills significantly more than found for controls. This study supports the hypothesis that faulty timing in synchronizing the activity of magnocellular with parvocellular visual pathways is a fundamental cause of dyslexia, and argues against the assumption that reading deficiencies in dyslexia are caused by phonological deficits. This study demonstrates that visual movement direction-discrimination can be used to not only detect dyslexia early, but also for its successful treatment, so that reading problems do not prevent children from readily learning.

Modeling and visualizing cell type switching.

PubMed

Ghaffarizadeh, Ahmadreza; Podgorski, Gregory J; Flann, Nicholas S

2014-01-01

Understanding cellular differentiation is critical in explaining development and for taming diseases such as cancer. Differentiation is conventionally represented using bifurcating lineage trees. However, these lineage trees cannot readily capture or quantify all the types of transitions now known to occur between cell types, including transdifferentiation or differentiation off standard paths. This work introduces a new analysis and visualization technique that is capable of representing all possible transitions between cell states compactly, quantitatively, and intuitively. This method considers the regulatory network of transcription factors that control cell type determination and then performs an analysis of network dynamics to identify stable expression profiles and the potential cell types that they represent. A visualization tool called CellDiff3D creates an intuitive three-dimensional graph that shows the overall direction and probability of transitions between all pairs of cell types within a lineage. In this study, the influence of gene expression noise and mutational changes during myeloid cell differentiation are presented as a demonstration of the CellDiff3D technique, a new approach to quantify and envision all possible cell state transitions in any lineage network.

Visualization of self-heating of an all climate battery by infrared thermography

NASA Astrophysics Data System (ADS)

Zhang, Guangsheng; Tian, Hua; Ge, Shanhai; Marple, Dan; Sun, Fengchun; Wang, Chao-Yang

2018-02-01

Self-heating Li-ion battery (SHLB), a.k.a. all climate battery, has provided a novel and practical solution to the low temperature power loss challenge. During its rapid self-heating, it is critical to keep the heating process and temperature distributions uniform for superior battery performance, durability and safety. Through infrared thermography of an experimental SHLB cell activated from various low ambient temperatures, we find that temperature distribution is uniform over the active electrode area, suggesting uniform heating. We also find that a hot spot exists at the activation terminal during self-heating, which provides diagnostics for improvement of next generation SHLB cells without the hot spot.

New apparatus of single particle trap system for aerosol visualization

NASA Astrophysics Data System (ADS)

Higashi, Hidenori; Fujioka, Tomomi; Endo, Tetsuo; Kitayama, Chiho; Seto, Takafumi; Otani, Yoshio

2014-08-01

Control of transport and deposition of charged aerosol particles is important in various manufacturing processes. Aerosol visualization is an effective method to directly observe light scattering signal from laser-irradiated single aerosol particle trapped in a visualization cell. New single particle trap system triggered by light scattering pulse signal was developed in this study. The performance of the device was evaluated experimentally. Experimental setup consisted of an aerosol generator, a differential mobility analyzer (DMA), an optical particle counter (OPC) and the single particle trap system. Polystylene latex standard (PSL) particles (0.5, 1.0 and 2.0 μm) were generated and classified according to the charge by the DMA. Singly charged 0.5 and 1.0 μm particles and doubly charged 2.0 μm particles were used as test particles. The single particle trap system was composed of a light scattering signal detector and a visualization cell. When the particle passed through the detector, trigger signal with a given delay time sent to the solenoid valves upstream and downstream of the visualization cell for trapping the particle in the visualization cell. The motion of particle in the visualization cell was monitored by CCD camera and the gravitational settling velocity and the electrostatic migration velocity were measured from the video image. The aerodynamic diameter obtained from the settling velocity was in good agreement with Stokes diameter calculated from the electrostatic migration velocity for individual particles. It was also found that the aerodynamic diameter obtained from the settling velocity was a one-to-one function of the scattered light intensity of individual particles. The applicability of this system will be discussed.

Protein-Coupled Fluorescent Probe To Visualize Potassium Ion Transition on Cellular Membranes.

PubMed

Hirata, Tomoya; Terai, Takuya; Yamamura, Hisao; Shimonishi, Manabu; Komatsu, Toru; Hanaoka, Kenjiro; Ueno, Tasuku; Imaizumi, Yuji; Nagano, Tetsuo; Urano, Yasuteru

2016-03-01

K(+) is the most abundant metal ion in cells, and changes of [K(+)] around cell membranes play important roles in physiological events. However, there is no practical method to selectively visualize [K(+)] at the surface of cells. To address this issue, we have developed a protein-coupled fluorescent probe for K(+), TLSHalo. TLSHalo is responsive to [K(+)] in the physiological range, with good selectivity over Na(+) and retains its K(+)-sensing properties after covalent conjugation with HaloTag protein. By using cells expressing HaloTag on the plasma membrane, we successfully directed TLSHalo specifically to the outer surface of target cells. This enabled us to visualize localized extracellular [K(+)] change with TLSHalo under a fluorescence microscope in real time. To confirm the experimental value of this system, we used TLSHalo to monitor extracellular [K(+)] change induced by K(+) ionophores or by activation of a native Ca(2+)-dependent K(+) channel (BK channel). Further, we show that K(+) efflux via BK channel induced by electrical stimulation at the bottom surface of the cells can be visualized with TLSHalo by means of total internal reflection fluorescence microscope (TIRFM) imaging. Our methodology should be useful to analyze physiological K(+) dynamics with high spatiotemporal resolution.

Development of bimolecular fluorescence complementation using rsEGFP2 for detection and super-resolution imaging of protein-protein interactions in live cells

PubMed Central

Wang, Sheng; Ding, Miao; Chen, Xuanze; Chang, Lei; Sun, Yujie

2017-01-01

Direct visualization of protein-protein interactions (PPIs) at high spatial and temporal resolution in live cells is crucial for understanding the intricate and dynamic behaviors of signaling protein complexes. Recently, bimolecular fluorescence complementation (BiFC) assays have been combined with super-resolution imaging techniques including PALM and SOFI to visualize PPIs at the nanometer spatial resolution. RESOLFT nanoscopy has been proven as a powerful live-cell super-resolution imaging technique. With regard to the detection and visualization of PPIs in live cells with high temporal and spatial resolution, here we developed a BiFC assay using split rsEGFP2, a highly photostable and reversibly photoswitchable fluorescent protein previously developed for RESOLFT nanoscopy. Combined with parallelized RESOLFT microscopy, we demonstrated the high spatiotemporal resolving capability of a rsEGFP2-based BiFC assay by detecting and visualizing specifically the heterodimerization interactions between Bcl-xL and Bak as well as the dynamics of the complex on mitochondria membrane in live cells. PMID:28663931

Human Pluripotent Stem-Cell-Derived Cortical Neurons Integrate Functionally into the Lesioned Adult Murine Visual Cortex in an Area-Specific Way.

PubMed

Espuny-Camacho, Ira; Michelsen, Kimmo A; Linaro, Daniele; Bilheu, Angéline; Acosta-Verdugo, Sandra; Herpoel, Adèle; Giugliano, Michele; Gaillard, Afsaneh; Vanderhaeghen, Pierre

2018-05-29

The transplantation of pluripotent stem-cell-derived neurons constitutes a promising avenue for the treatment of several brain diseases. However, their potential for the repair of the cerebral cortex remains unclear, given its complexity and neuronal diversity. Here, we show that human visual cortical cells differentiated from embryonic stem cells can be transplanted and can integrate successfully into the lesioned mouse adult visual cortex. The transplanted human neurons expressed the appropriate repertoire of markers of six cortical layers, projected axons to specific visual cortical targets, and were synaptically active within the adult brain. Moreover, transplant maturation and integration were much less efficient following transplantation into the lesioned motor cortex, as previously observed for transplanted mouse cortical neurons. These data constitute an important milestone for the potential use of human PSC-derived cortical cells for the reassembly of cortical circuits and emphasize the importance of cortical areal identity for successful transplantation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Assessment of Human Visual Performance with a Swept Evoked Potential Technique

DTIC Science & Technology

1984-07-01

obtained in naive patients. Retinitis pigmentosa patients with < 20/50 vision have shown contrast sensitivity losses at the higher spatial frequencies...X and Y visual subsystems The new visual duplicity. Th« observation that cat retinal ganglion cells can be divided into those which sum luminous...bias in retinal ganglion cells (cat: Levick & Thibos, 1980; monkey: DeMonasterio, 1978). The bias is weak. In cat, when the stimulus orientation was

Audio visual speech source separation via improved context dependent association model

NASA Astrophysics Data System (ADS)

Kazemi, Alireza; Boostani, Reza; Sobhanmanesh, Fariborz

2014-12-01

In this paper, we exploit the non-linear relation between a speech source and its associated lip video as a source of extra information to propose an improved audio-visual speech source separation (AVSS) algorithm. The audio-visual association is modeled using a neural associator which estimates the visual lip parameters from a temporal context of acoustic observation frames. We define an objective function based on mean square error (MSE) measure between estimated and target visual parameters. This function is minimized for estimation of the de-mixing vector/filters to separate the relevant source from linear instantaneous or time-domain convolutive mixtures. We have also proposed a hybrid criterion which uses AV coherency together with kurtosis as a non-Gaussianity measure. Experimental results are presented and compared in terms of visually relevant speech detection accuracy and output signal-to-interference ratio (SIR) of source separation. The suggested audio-visual model significantly improves relevant speech classification accuracy compared to existing GMM-based model and the proposed AVSS algorithm improves the speech separation quality compared to reference ICA- and AVSS-based methods.

Cell-fusion method to visualize interphase nuclear pore formation.

PubMed

Maeshima, Kazuhiro; Funakoshi, Tomoko; Imamoto, Naoko

2014-01-01

In eukaryotic cells, the nucleus is a complex and sophisticated organelle that organizes genomic DNA to support essential cellular functions. The nuclear surface contains many nuclear pore complexes (NPCs), channels for macromolecular transport between the cytoplasm and nucleus. It is well known that the number of NPCs almost doubles during interphase in cycling cells. However, the mechanism of NPC formation is poorly understood, presumably because a practical system for analysis does not exist. The most difficult obstacle in the visualization of interphase NPC formation is that NPCs already exist after nuclear envelope formation, and these existing NPCs interfere with the observation of nascent NPCs. To overcome this obstacle, we developed a novel system using the cell-fusion technique (heterokaryon method), previously also used to analyze the shuttling of macromolecules between the cytoplasm and the nucleus, to visualize the newly synthesized interphase NPCs. In addition, we used a photobleaching approach that validated the cell-fusion method. We recently used these methods to demonstrate the role of cyclin-dependent protein kinases and of Pom121 in interphase NPC formation in cycling human cells. Here, we describe the details of the cell-fusion approach and compare the system with other NPC formation visualization methods. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of 2 oral ultrasonography contrast agents: simethicone-coated cellulose and simethicone-water rotation in improving pancreatic visualization.

PubMed

Ishigami, Kousei; Abu-Yousef, Dina M; Kao, Simon C S; Abu-Yousef, Monzer M

2014-06-01

The purpose of this study was to prospectively compare the efficacy of 2 oral ultrasonography (US) contrast agents (simethicone-water rotation [SWR] and simethicone-coated cellulose [SCC]) in improving visualization of the pancreas. Two sessions (SWR and SCC) of transabdominal US studies were performed on 38 healthy volunteers. In each session, US images were obtained in precontrast supine and upright positions and postcontrast supine and upright positions. The visualization of the pancreas was graded on a scale of 1 to 5 (1 = nonvisualization, 5 = excellent visualization), grading the head, body, and tail separately. In the supine position, SWR significantly improved the visualization of the pancreatic head, body, and tail, whereas there were no significant differences between SCC and precontrast images. Simethicone-water rotation showed significantly better visualization than SCC. The average scores of the head, body, and tail of the pancreas that graded 4 or more were 15.8% of precontrast, 21.1% of SCC, and 50% of SWR. In the upright position, both SWR and SCC significantly improved the visualization of the pancreas, except for the pancreatic body on SCC. There were no significant differences between SWR and SCC. The average scores that graded 4 or more were 26.3% of precontrast, 57.9% of SCC, and 65.8% of SWR. Simethicone-water rotation was more effective than SCC in improving the visualization of the pancreas.

Activity of 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 645 neurons in area 6 of five cats trained in oculomotor tasks. The area we recorded from corresponds well with territories believed to contain the feline homologue of the frontal eye fields observed in primates. Despite an expectation that cells with pre-saccadic activity would be common, only a small fraction (approximately 5%) of the cells displayed activity that could be linked to subsequent saccadic eye movements. These pre-motor cells appeared to be distributed over a broad region of cortex mixed in with other cell types. As in primates, saccade-related activity tended to occur only during "purposeful" saccades. At least 30% (208/645) of the neurons were visual, with many of these cells possessing huge receptive fields that appeared to include the entire contralateral visual field. Visual responsiveness was generally attenuated by fixation during the oculomotor tasks. Although attentional mechanisms may play a role in this attenuation, this cortical area also exhibits powerful lateral interactions in which spatially displaced visual stimuli suppress each other. Most cells, visually responsive or not, were affected by fixation. Nearly equal proportions of cells showed increases or decreases in activity during fixation. For many of the cells affected by fixation, the source of this modulation appears to reflect cognitive, rather than sensory or motor processes. This included cells that showed anticipatory activity, and cells that responded to the reward only when it was presented in the context of the task. Based on the paucity of pre-saccadic neurons, it would be difficult to conclude that this region of cortex in the cat is homologous to the frontal eye fields of the monkey. However, when considered in the context of differences in the oculomotor habits of these two animals, we believe the homology fits. In addition to pre-motor neurons, the properties of several other cell types found in this area could contribute to the control of gaze.

Integration trumps selection in object recognition.

PubMed

Saarela, Toni P; Landy, Michael S

2015-03-30

Finding and recognizing objects is a fundamental task of vision. Objects can be defined by several "cues" (color, luminance, texture, etc.), and humans can integrate sensory cues to improve detection and recognition [1-3]. Cortical mechanisms fuse information from multiple cues [4], and shape-selective neural mechanisms can display cue invariance by responding to a given shape independent of the visual cue defining it [5-8]. Selective attention, in contrast, improves recognition by isolating a subset of the visual information [9]. Humans can select single features (red or vertical) within a perceptual dimension (color or orientation), giving faster and more accurate responses to items having the attended feature [10, 11]. Attention elevates neural responses and sharpens neural tuning to the attended feature, as shown by studies in psychophysics and modeling [11, 12], imaging [13-16], and single-cell and neural population recordings [17, 18]. Besides single features, attention can select whole objects [19-21]. Objects are among the suggested "units" of attention because attention to a single feature of an object causes the selection of all of its features [19-21]. Here, we pit integration against attentional selection in object recognition. We find, first, that humans can integrate information near optimally from several perceptual dimensions (color, texture, luminance) to improve recognition. They cannot, however, isolate a single dimension even when the other dimensions provide task-irrelevant, potentially conflicting information. For object recognition, it appears that there is mandatory integration of information from multiple dimensions of visual experience. The advantage afforded by this integration, however, comes at the expense of attentional selection. Copyright © 2015 Elsevier Ltd. All rights reserved.

Integration trumps selection in object recognition

PubMed Central

Saarela, Toni P.; Landy, Michael S.

2015-01-01

Summary Finding and recognizing objects is a fundamental task of vision. Objects can be defined by several “cues” (color, luminance, texture etc.), and humans can integrate sensory cues to improve detection and recognition [1–3]. Cortical mechanisms fuse information from multiple cues [4], and shape-selective neural mechanisms can display cue-invariance by responding to a given shape independent of the visual cue defining it [5–8]. Selective attention, in contrast, improves recognition by isolating a subset of the visual information [9]. Humans can select single features (red or vertical) within a perceptual dimension (color or orientation), giving faster and more accurate responses to items having the attended feature [10,11]. Attention elevates neural responses and sharpens neural tuning to the attended feature, as shown by studies in psychophysics and modeling [11,12], imaging [13–16], and single-cell and neural population recordings [17,18]. Besides single features, attention can select whole objects [19–21]. Objects are among the suggested “units” of attention because attention to a single feature of an object causes the selection of all of its features [19–21]. Here, we pit integration against attentional selection in object recognition. We find, first, that humans can integrate information near-optimally from several perceptual dimensions (color, texture, luminance) to improve recognition. They cannot, however, isolate a single dimension even when the other dimensions provide task-irrelevant, potentially conflicting information. For object recognition, it appears that there is mandatory integration of information from multiple dimensions of visual experience. The advantage afforded by this integration, however, comes at the expense of attentional selection. PMID:25802154

Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor angiogenesis after chemotherapy as visualized by real-time FUCCI imaging.

PubMed

Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

2017-03-04

We previously demonstrated that quiescent cancer cells in a tumor are resistant to conventional chemotherapy as visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). We also showed that proliferating cancer cells exist in a tumor only near nascent vessels or on the tumor surface as visualized with FUCCI and green fluorescent protein (GFP)-expressing tumor vessels. In the present study, we show the relationship between cell-cycle phase and chemotherapy-induced tumor angiogenesis using in vivo FUCCI real-time imaging of the cell cycle and nestin-driven GFP to detect nascent blood vessels. We observed that chemotherapy-treated tumors, consisting of mostly of quiescent cancer cells after treatment, had much more and deeper tumor vessels than untreated tumors. These newly-vascularized cancer cells regrew rapidly after chemotherapy. In contrast, formerly quiescent cancer cells decoyed to S/G 2 phase by a telomerase-dependent adenovirus did not induce tumor angiogenesis. The present results further demonstrate the importance of the cancer-cell position in the cell cycle in order that chemotherapy be effective and not have the opposite effect of stimulating tumor angiogenesis and progression.

Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor angiogenesis after chemotherapy as visualized by real-time FUCCI imaging

PubMed Central

Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M.

2017-01-01

ABSTRACT We previously demonstrated that quiescent cancer cells in a tumor are resistant to conventional chemotherapy as visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). We also showed that proliferating cancer cells exist in a tumor only near nascent vessels or on the tumor surface as visualized with FUCCI and green fluorescent protein (GFP)-expressing tumor vessels. In the present study, we show the relationship between cell-cycle phase and chemotherapy-induced tumor angiogenesis using in vivo FUCCI real-time imaging of the cell cycle and nestin-driven GFP to detect nascent blood vessels. We observed that chemotherapy-treated tumors, consisting of mostly of quiescent cancer cells after treatment, had much more and deeper tumor vessels than untreated tumors. These newly-vascularized cancer cells regrew rapidly after chemotherapy. In contrast, formerly quiescent cancer cells decoyed to S/G2 phase by a telomerase-dependent adenovirus did not induce tumor angiogenesis. The present results further demonstrate the importance of the cancer-cell position in the cell cycle in order that chemotherapy be effective and not have the opposite effect of stimulating tumor angiogenesis and progression. PMID:27715464

Improved penile histology by phalloidin stain: circular and longitudinal cavernous smooth muscles, dual-endothelium arteries, and erectile dysfunction-associated changes.

PubMed

Lin, Guiting; Qiu, Xuefeng; Fandel, Thomas M; Albersen, Maarten; Wang, Zhong; Lue, Tom F; Lin, Ching-Shwun

2011-10-01

To investigate whether fluorochrome-conjugated phalloidin can delineate cavernous smooth muscle (CSM) cells and whether it can be combined with immunofluorescence (IF) staining to quantify erectile dysfunction (ED)-associated changes. ED was induced by cavernous nerve crush in rats. Penile tissues of control and ED rats were stained with Alexa-488-conjugated phalloidin and/or with antibodies against rat endothelial cell antigen (RECA), CD31, neuronal nitric oxide synthase (nNOS), and collagen-IV (Col-IV). Phalloidin was able to delineate CSM as composed of a circular and a longitudinal compartment. When combined with IF stain for CD31 or RECA, it helped the identification of the helicine arteries as covered by endothelial cells on both sides of the smooth muscle layer. When combined with IF stain for nNOS, it helped the identification that nNOS-positive nerves were primarily localized within the dorsal nerves and in the adventitia of dorsal arteries. When combined with IF stain for Col-IV, it helped identify that Col-IV was localized around smooth muscles and beneath the endothelium. Phalloidin also facilitated the quantitative analysis of ED-related changes in the penis. In rats with cavernous nerve injury, RECA or Col-IV expression did not change significantly, but CSM and nNOS nerve contents decreased significantly. Phalloidin stain improved penile histology, enabling the visualization of the circular and longitudinal compartments in the CSM. It also worked synergistically with IF stain, permitting the visualization of the dual endothelial covering in helicine arteries, and facilitating the quantification of ED-related histologic changes. Copyright © 2011 Elsevier Inc. All rights reserved.

Predictors of visual outcome in patients operated for craniopharyngioma - a Danish national study.

PubMed

Jacobsen, Mads Forslund; Thomsen, Ann Sofia Skou; Bach-Holm, Daniella; Doroudian, Ghazaleh; Nissen, Kamilla Rothe; Fugleholm, Kåre; Poulsgaard, Lars; Siersma, Volkert; Heegaard, Steffen

2018-02-01

Craniopharyngioma often causes visual loss due to the close relation to the anterior visual pathways. This study investigates the incidence and predictors of visual outcomes in patients with craniopharyngioma. Data from sixty-six patients who underwent surgery for craniopharyngioma from 2009 to 2013 in Denmark were reviewed. Primary outcomes were visual acuity (VA) and visual field (VF) defects from pre-and postoperative visits. Secondary outcomes were optic nerve atrophy (OA) and papilledema. Fifty-eight patients were included. The VA of the patients 1-year after surgery improved by -0.16 log(MAR) (95%CI: -0.30 to -0.02; p = 0.0266). Visual field (VF) defects worsened in 17 eyes (30%), remained stable in 21 eyes (37%) and improved in 19 eyes (33%). The presence of papilledema and the absence of OA were significantly correlated with an improvement in VA postoperatively (p = 0.011 and p = 0.011, respectively). Patients undergoing surgery within a week or less after their first ophthalmological examination had a significant improvement in VA (-0.36; 95%CI: -0.62 to -0.09; p = 0.0099). Patients undergoing surgery using a subfrontal approach also showed improvement in VA (p = 0.048). Tumour recurrence had a significantly worse VA outcome (p = 0.0074). Patients show a slight improvement in VA 1-year after operation for craniopharyngioma. The presence of papilledema and early surgical intervention is associated with a significant improvement in VA. Early involvement of a dedicated ophthalmologist is recommended to secure an early detection of a visual decline and potential tumour recurrence. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Visual acuity, endothelial cell density and polymegathism after iris-fixated lens implantation.

PubMed

Nassiri, Nader; Ghorbanhosseini, Saeedeh; Jafarzadehpur, Ebrahim; Kavousnezhad, Sara; Nassiri, Nariman; Sheibani, Kourosh

2018-01-01

The purpose of this study was to evaluate the visual acuity as well as endothelial cell density (ECD) and polymegathism after iris-fixated lens (Artiflex ® AC 401) implantation for correction of moderate to high myopia. In this retrospective cross-sectional study, 55 eyes from 29 patients undergoing iris-fixated lens implantation for correction of myopia (-5.00 to -15.00 D) from 2007 to 2014 were evaluated. Uncorrected visual acuity, best spectacle-corrected visual acuity, refraction, ECD and polymegathism (coefficient of variation [CV] in the sizes of endothelial cells) were measured preoperatively and 6 months postoperatively. In the sixth month of follow-up, the uncorrected vision acuity was 20/25 or better in 81.5% of the eyes. The best-corrected visual acuity was 20/30 or better in 96.3% of the eyes, and more than 92% of the eyes had a refraction score of ±1 D from the target refraction. The mean corneal ECD of patients before surgery was 2,803±339 cells/mm 2 , which changed to 2,744±369 cells/mm 2 six months after surgery ( p =0.142). CV in the sizes of endothelial cells before the surgery was 25.7%±7.1% and six months after surgery it was 25.9%±5.4% ( p =0.857). Artiflex iris-fixated lens implantation is a suitable and predictable method for correction of moderate to high myopia. There was no statistically significant change in ECD and polymegathism (CV in the sizes of endothelial cells) after 6 months of follow-up.

Segregation of Form, Color, Movement, and Depth: Anatomy, Physiology, and Perception

NASA Astrophysics Data System (ADS)

Livingstone, Margaret; Hubel, David

1988-05-01

Anatomical and physiological observations in monkeys indicate that the primate visual system consists of several separate and independent subdivisions that analyze different aspects of the same retinal image: cells in cortical visual areas 1 and 2 and higher visual areas are segregated into three interdigitating subdivisions that differ in their selectivity for color, stereopsis, movement, and orientation. The pathways selective for form and color seem to be derived mainly from the parvocellular geniculate subdivisions, the depth- and movement-selective components from the magnocellular. At lower levels, in the retina and in the geniculate, cells in these two subdivisions differ in their color selectivity, contrast sensitivity, temporal properties, and spatial resolution. These major differences in the properties of cells at lower levels in each of the subdivisions led to the prediction that different visual functions, such as color, depth, movement, and form perception, should exhibit corresponding differences. Human perceptual experiments are remarkably consistent with these predictions. Moreover, perceptual experiments can be designed to ask which subdivisions of the system are responsible for particular visual abilities, such as figure/ground discrimination or perception of depth from perspective or relative movement--functions that might be difficult to deduce from single-cell response properties.

Single-Cell Analysis of Experience-Dependent Transcriptomic States in Mouse Visual Cortex

PubMed Central

Hrvatin, Sinisa; Hochbaum, Daniel R.; Nagy, M. Aurel; Cicconet, Marcelo; Robertson, Keiramarie; Cheadle, Lucas; Zilionis, Rapolas; Ratner, Alex; Borges-Monroy, Rebeca; Klein, Allon M.; Sabatini, Bernardo L.; Greenberg, Michael E.

2017-01-01

Activity-dependent transcriptional responses shape cortical function. However, we lack a comprehensive understanding of the diversity of these responses across the full range of cortical cell types, and how these changes contribute to neuronal plasticity and disease. Here we applied high-throughput single-cell RNA-sequencing to investigate the breadth of transcriptional changes that occur across cell types in mouse visual cortex following exposure to light. We identified significant and divergent transcriptional responses to stimulation in each of the 30 cell types characterized, revealing 611 stimulus-responsive genes. Excitatory pyramidal neurons exhibit inter- and intra-laminar heterogeneity in the induction of stimulus responsive genes. Non-neuronal cells demonstrated clear transcriptional responses that may regulate experience-dependent changes in neurovascular coupling and myelination. Together, these results reveal the dynamic landscape of stimulus-dependent transcriptional changes that occur across cell types in visual cortex, which are likely critical for cortical function and may be sites of de-regulation in developmental brain disorders. PMID:29230054

Targeting neuronal gap junctions in mouse retina offers neuroprotection in glaucoma

PubMed Central

Kumar, Sandeep; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Viswanathan, Suresh; Bloomfield, Stewart A.

2017-01-01

The progressive death of retinal ganglion cells and resulting visual deficits are hallmarks of glaucoma, but the underlying mechanisms remain unclear. In many neurodegenerative diseases, cell death induced by primary insult is followed by a wave of secondary loss. Gap junctions (GJs), intercellular channels composed of subunit connexins, can play a major role in secondary cell death by forming conduits through which toxic molecules from dying cells pass to and injure coupled neighbors. Here we have shown that pharmacological blockade of GJs or genetic ablation of connexin 36 (Cx36) subunits, which are highly expressed by retinal neurons, markedly reduced loss of neurons and optic nerve axons in a mouse model of glaucoma. Further, functional parameters that are negatively affected in glaucoma, including the electroretinogram, visual evoked potential, visual spatial acuity, and contrast sensitivity, were maintained at control levels when Cx36 was ablated. Neuronal GJs may thus represent potential therapeutic targets to prevent the progressive neurodegeneration and visual impairment associated with glaucoma. PMID:28604388

Outcomes of descemet stripping automated endothelial keratoplasty using imported donor corneas.

PubMed

Lekhanont, Kaevalin; Vanikieti, Kavin; Nimvorapun, Nutthida; Chuckpaiwong, Varintorn

2017-04-05

The lack of development of local donor tissue acquisition in several regions of the world has resulted in the necessity of performing keratoplasty with imported donor corneas. The greatest concern about the use of donor corneas supplied by foreign eye banks is the effect of the increased donor death-to-operation time which inevitably occurs during the tissue recovery, tissue processing, and tissue transfer between the countries. The purpose of this study was to report the outcomes of descemet stripping automated endothelial keratoplasty (DSAEK) using imported donor corneas. This retrospective, non-comparative case series investigated the outcomes of the 102 consecutive DSAEK procedures using imported donor corneas performed at a single university-based hospital between August 2006-2014. The main outcome measures were postoperative best-corrected visual acuity (BCVA), endothelial cell density (ECD), and complications. The mean death-to-operation time was 9.52 ± 1.48 days (range, 8-13). The mean preoperative ECD was 2761 ± 285 cells/mm 2 . Fuchs' endothelial dystrophy was the predominant indication for grafting. The mean follow-up duration was 65.3 months. Ninety-three eyes had improved vision postoperatively (91.18%). BCVA unchanged in 3 eyes due to preexisting macular scar and advanced glaucoma. Primary graft failure occurred in 6 eyes (5.88%). Of the 93 eyes with improved BCVA, 100% had their best corrected vision within the first 1 year. The mean ECD at 6, 12, 24, 36, and 60 months after surgery was 1762 ± 294 cells/mm 2 , 1681 ± 284 cells/mm 2 , 1579 ± 209 cells/mm 2 , 1389 ± 273 cells/mm 2 , and 1251 ± 264 cells/mm 2 respectively. The mean ECD loss at 6 months, 1 year, 2 years, 3 years, and 5 years after surgery was 36.2%, 39.1%, 42.8%, 49.7%, and 54.7% respectively. The most common complication was graft detachment/dislocation (10.78%). There were no cases of any postoperative infection. DSAEK with imported donor corneas provides rapid and good visual rehabilitation. The percentages of endothelial cell loss were comparable to those achieved in Western series using domestic corneas in which fresher tissues were available for transplantation.

Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits

PubMed Central

Xu, Hong-Ping; Burbridge, Timothy J.; Ye, Meijun; Chen, Minggang; Ge, Xinxin; Zhou, Z. Jimmy

2016-01-01

Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical, in vitro and in vivo electrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of β2 subunits of nicotinic acetylcholine receptors (β2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that β2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the “recurrent network” model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development. SIGNIFICANCE STATEMENT Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic “retinal waves” are initiated in starburst amacrine cells and propagate to retinal ganglion cells and higher-order visual areas, but the mechanism responsible for creating their unique and critical activity pattern is incompletely understood. We demonstrate that cholinergic wave patterns are dictated by recurrent connectivity within starburst amacrine cells, and retinal ganglion cells act as “readouts” of patterned activity. We also show that eye-specific segregation occurs normally without glutamatergic waves, but elimination of both cholinergic and glutamatergic waves completely disrupts visual circuit development. These results suggest that each retinal wave pattern during development is optimized for concurrently refining multiple visual circuits. PMID:27030771

Acyclovir resistant acute herpes simplex encephalitis associated with acute retinal necrosis: A case report and review of the literature.

PubMed

Ogura, Haruchika; Fukae, Jiro; Kimura, Satoshi; Aoki, Mikiko; Nabeshima, Kazuki; Tsuboi, Yoshio

2017-05-27

A 55-year-old man was admitted to our hospital for investigation of high fever, decreased consciousness and bilateral visual impairment. His cerebrospinal fluid analysis revealed pleocytosis of mononuclear cells and an increased protein concentration. FLAIR images revealed multiple high-intensity lesions in the frontal lobe, part of which was enhanced with gadolinium. Despite initiating treatment with acyclovir and corticosteroids, his consciousness and visual acuity deteriorated. Immunopathological examination of brain biopsies showed numerous herpes simplex virus type 2-positive neurons and macrophages, leading to a diagnosis of herpes simplex encephalitis (HSE). Fundoscopic examination revealed multiple foci of retinitis with vasculopathies, and inflammation in the anterior chamber and vitreous, indicating acute retinal necrosis (ARN). Foscarnet treatment was initiated in place of acyclovir and his consciousness improved, with a slight improvement in visual acuity. ARN is typically caused by a herpes virus infection limited to the eyeball, and rarely in combination with HSE. In such cases, there is a latency of approximately 2-4 weeks between ARN and the onset of encephalitis. Our case is unique in that HSE and ARN developed simultaneously, and it highlights that there may not always be a latency between the onsets of the two disorders. Finally, foscarnet should be considered in cases of HSE and ARN with acyclovir resistance.

Survival and Functionality of hESC-Derived Retinal Pigment Epithelium Cells Cultured as a Monolayer on Polymer Substrates Transplanted in RCS Rats.

PubMed

Thomas, Biju B; Zhu, Danhong; Zhang, Li; Thomas, Padmaja B; Hu, Yuntao; Nazari, Hossein; Stefanini, Francisco; Falabella, Paulo; Clegg, Dennis O; Hinton, David R; Humayun, Mark S

2016-05-01

To determine the safety, survival, and functionality of human embryonic stem cell-derived RPE (hESC-RPE) cells seeded on a polymeric substrate (rCPCB-RPE1 implant) and implanted into the subretinal (SR) space of Royal College of Surgeons (RCS) rats. Monolayers of hESC-RPE cells cultured on parylene membrane were transplanted into the SR space of 4-week-old RCS rats. Group 1 (n = 46) received vitronectin-coated parylene membrane without cells (rMSPM+VN), group 2 (n = 59) received rCPCB-RPE1 implants, and group 3 (n = 13) served as the control group. Animals that are selected based on optical coherence tomography screening were subjected to visual function assays using optokinetic (OKN) testing and superior colliculus (SC) electrophysiology. At approximately 25 weeks of age (21 weeks after surgery), the eyes were examined histologically for cell survival, phagocytosis, and local toxicity. Eighty-seven percent of the rCPCB-RPE1-implanted animals showed hESC-RPE survivability. Significant numbers of outer nuclear layer cells were rescued in both group 1 (rMSPM+VN) and group 2 (rCPCB-RPE1) animals. A significantly higher ratio of rod photoreceptor cells to cone photoreceptor cells was found in the rCPCB-RPE1-implanted group. Animals with rCPCB-RPE1 implant showed hESC-RPE cells containing rhodopsin-positive particles in immunohistochemistry, suggesting phagocytic function. Superior colliculus mapping data demonstrated that a significantly higher number of SC sites responded to light stimulus at a lower luminance threshold level in the rCPCB-RPE1-implanted group. Optokinetic data suggested both implantation groups showed improved visual acuity. These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunction rat model.

Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading (TED)

PubMed Central

Samtleben, Samira; Jaepel, Juliane; Fecher, Caroline; Andreska, Thomas; Rehberg, Markus; Blum, Robert

2013-01-01

Visualization of calcium dynamics is important to understand the role of calcium in cell physiology. To examine calcium dynamics, synthetic fluorescent Ca2+ indictors have become popular. Here we demonstrate TED (= targeted-esterase induced dye loading), a method to improve the release of Ca2+ indicator dyes in the ER lumen of different cell types. To date, TED was used in cell lines, glial cells, and neurons in vitro. TED bases on efficient, recombinant targeting of a high carboxylesterase activity to the ER lumen using vector-constructs that express Carboxylesterases (CES). The latest TED vectors contain a core element of CES2 fused to a red fluorescent protein, thus enabling simultaneous two-color imaging. The dynamics of free calcium in the ER are imaged in one color, while the corresponding ER structure appears in red. At the beginning of the procedure, cells are transduced with a lentivirus. Subsequently, the infected cells are seeded on coverslips to finally enable live cell imaging. Then, living cells are incubated with the acetoxymethyl ester (AM-ester) form of low-affinity Ca2+ indicators, for instance Fluo5N-AM, Mag-Fluo4-AM, or Mag-Fura2-AM. The esterase activity in the ER cleaves off hydrophobic side chains from the AM form of the Ca2+ indicator and a hydrophilic fluorescent dye/Ca2+ complex is formed and trapped in the ER lumen. After dye loading, the cells are analyzed at an inverted confocal laser scanning microscope. Cells are continuously perfused with Ringer-like solutions and the ER calcium dynamics are directly visualized by time-lapse imaging. Calcium release from the ER is identified by a decrease in fluorescence intensity in regions of interest, whereas the refilling of the ER calcium store produces an increase in fluorescence intensity. Finally, the change in fluorescent intensity over time is determined by calculation of ΔF/F0. PMID:23685703

Direct imaging of ER calcium with targeted-esterase induced dye loading (TED).

PubMed

Samtleben, Samira; Jaepel, Juliane; Fecher, Caroline; Andreska, Thomas; Rehberg, Markus; Blum, Robert

2013-05-07

Visualization of calcium dynamics is important to understand the role of calcium in cell physiology. To examine calcium dynamics, synthetic fluorescent Ca(2+) indictors have become popular. Here we demonstrate TED (= targeted-esterase induced dye loading), a method to improve the release of Ca(2+) indicator dyes in the ER lumen of different cell types. To date, TED was used in cell lines, glial cells, and neurons in vitro. TED bases on efficient, recombinant targeting of a high carboxylesterase activity to the ER lumen using vector-constructs that express Carboxylesterases (CES). The latest TED vectors contain a core element of CES2 fused to a red fluorescent protein, thus enabling simultaneous two-color imaging. The dynamics of free calcium in the ER are imaged in one color, while the corresponding ER structure appears in red. At the beginning of the procedure, cells are transduced with a lentivirus. Subsequently, the infected cells are seeded on coverslips to finally enable live cell imaging. Then, living cells are incubated with the acetoxymethyl ester (AM-ester) form of low-affinity Ca(2+) indicators, for instance Fluo5N-AM, Mag-Fluo4-AM, or Mag-Fura2-AM. The esterase activity in the ER cleaves off hydrophobic side chains from the AM form of the Ca(2+) indicator and a hydrophilic fluorescent dye/Ca(2+) complex is formed and trapped in the ER lumen. After dye loading, the cells are analyzed at an inverted confocal laser scanning microscope. Cells are continuously perfused with Ringer-like solutions and the ER calcium dynamics are directly visualized by time-lapse imaging. Calcium release from the ER is identified by a decrease in fluorescence intensity in regions of interest, whereas the refilling of the ER calcium store produces an increase in fluorescence intensity. Finally, the change in fluorescent intensity over time is determined by calculation of ΔF/F0.

Can Visual Illusions Be Used to Facilitate Sport Skill Learning?

PubMed

Cañal-Bruland, Rouwen; van der Meer, Yor; Moerman, Jelle

2016-01-01

Recently it has been reported that practicing putting with visual illusions that make the hole appear larger than it actually is leads to longer-lasting performance improvements. Interestingly, from a motor control and learning perspective, it may be possible to actually predict the opposite to occur, as facing a smaller appearing target should enforce performers to be more precise. To test this idea the authors invited participants to practice an aiming task (i.e., a marble-shooting task) with either a visual illusion that made the target appear larger or a visual illusion that made the target appear smaller. They applied a pre-post test design, included a control group training without any illusory effects and increased the amount of practice to 450 trials. In contrast to earlier reports, the results revealed that the group that trained with the visual illusion that made the target look smaller improved performance from pre- to posttest, whereas the group practicing with visual illusions that made the target appear larger did not show any improvements. Notably, also the control group improved from pre- to posttest. The authors conclude that more research is needed to improve our understanding of whether and how visual illusions may be useful training tools for sport skill learning.

The Effects of Realism in Learning with Dynamic Visualizations

ERIC Educational Resources Information Center

Scheiter, Katharina; Gerjets, Peter; Huk, Thomas; Imhof, Birgit; Kammerer, Yvonne

2009-01-01

Two experiments are reported that investigated the relative effectiveness of a realistic dynamic visualization as opposed to a schematic visualization for learning about cell replication (mitosis). In Experiment 1, 37 university students watched either realistic or schematic visualizations. Students' subjective task demands ratings as well as…

Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intrapatient comparative study.

PubMed

Sadoughi, Mohammad Mehdi; Einollahi, Bahram; Baradaran-Rafii, Alireza; Roshandel, Danial; Hasani, Hamidreza; Nazeri, Mehrdad

2018-02-01

To compare the outcomes of the conventional and accelerated corneal collagen cross-linking (CXL) in patients with bilateral progressive keratoconus (KC). Fifteen consecutive patients with bilateral progressive KC were enrolled. In each patient, the fellow eyes were randomly assigned to the conventional CXL (3 mW/cm 2 for 30 min) or accelerated CXL (ACXL) (9 mW/cm 2 for 10 min) groups. Manifest refraction; uncorrected and corrected distant visual acuity; maximum and mean keratometry; corneal hysteresis and corneal resistance factor; endothelial cell density and morphology; central corneal thickness; and wavefront aberrations were measured before and 12 months after the CXL. Manifest refraction spherical equivalent and refractive cylinder improved significantly only in conventional group. Uncorrected and corrected distant visual acuity did not change significantly in either group. Also there was no significant change in the maximum and mean keratometry after 12 months. There was significant decrease in central corneal thickness in both groups which was more prominent in conventional group. Endothelial cell density reduced only in the conventional group which was not statistically significant (P = 0.147). CH, CRF, and wavefront aberrations did not change significantly in either group. We did not observe any significant difference in the changes of the variables between the two groups. Accelerated CXL with 9 mW/cm 2 irradiation for 10 min had similar refractive, visual, keratometric, and aberrometric results and less adverse effects on the corneal thickness and endothelial cells as compared with the conventional method after 12 months follow-up. However, randomized clinical trials with longer follow-ups and larger sample sizes are needed.

A Two-Piece Microkeratome-Assisted Mushroom Keratoplasty Improves the Outcomes and Survival of Grafts Performed in Eyes with Diseased Stroma and Healthy Endothelium (An American Ophthalmological Society Thesis)

PubMed Central

Busin, Massimo; Madi, Silvana; Scorcia, Vincenzo; Santorum, Paolo; Nahum, Yoav

2015-01-01

Purpose: To test the hypothesis that a new microkeratome-assisted penetrating keratoplasty (PK) technique employing transplantation of a two-piece mushroom-shaped graft may result in better visual outcomes and graft survival rates than those of conventional PK. Methods: Retrospective chart review of 96 eyes at low risk and 76 eyes at high risk for immunologic rejection (all with full-thickness central corneal opacity and otherwise healthy endothelium) undergoing mushroom PK between 2004 and 2012 at our Institution. Outcome measures were best-corrected visual acuity (BCVA), refraction, corneal topography, endothelial cell density, graft rejection, and survival probability. Results: Five years postoperatively, BCVA of 20/40 and 20/20 was recorded in 100% and over 50% of eyes, respectively. Mean spherical equivalent of refractive error did not vary significantly over a 5-year period; astigmatism averaged always below 4 diopters, with no statistically significant change over time, and was of the regular type in over 90% of eyes. Endothelial cell density decreased to about 40% of the eye bank count 2 years after mushroom PK and did not change significantly thereafter. Five years postoperatively, probabilities of graft immunologic rejection and graft survival were below 5% and above 95%, respectively. There was no statistically significant difference in endothelial cell loss, graft rejection, and survival probability between low-risk and high-risk subgroups. Conclusions: Refractive and visual outcomes of mushroom PK compare favorably with those of conventional full-thickness keratoplasty. In eyes at high risk for immunologic rejection, mushroom PK provides a considerably higher probability of graft survival than conventional PK. PMID:26538771

Visual responses of neurones in the second visual area of flying foxes (Pteropus poliocephalus) after lesions of striate cortex

PubMed Central

Funk, Agnes P; Rosa, Marcello G P

1998-01-01

The first (V1) and second (V2) cortical visual areas exist in all mammals. However, the functional relationship between these areas varies between species. While in monkeys the responses of V2 cells depend on inputs from V1, in all non-primates studied so far V2 cells largely retain responsiveness to photic stimuli after destruction of V1.We studied the visual responsiveness of neurones in V2 of flying foxes after total or partial lesions of the primary visual cortex (V1). The main finding was that visual responses can be evoked in the region of V2 corresponding, in visuotopic co-ordinates, to the lesioned portion of V1 (‘lesion projection zone’; LPZ).The visuotopic organization of V2 was not altered by V1 lesions.The proportion of neurones with strong visual responses was significantly lower within the LPZs (31.5 %) than outside these zones, or in non-lesioned control hemispheres (> 70 %). LPZ cells showed weak direction and orientation bias, and responded consistently only at low spatial and temporal frequencies.The data demonstrate that the functional relationship between V1 and V2 of flying foxes resembles that observed in non-primate mammals. This observation contrasts with the ‘primate-like’ characteristics of the flying fox visual system reported by previous studies. PMID:9806999

Reading ability and retinal sensitivity after surgery for macular hole and macular pucker.

PubMed

Cappello, Ezio; Virgili, Gianni; Tollot, Luigina; Del Borrello, Michele; Menchini, Ugo; Zemella, Marco

2009-09-01

To assess whether reading ability and microperimetry improve as demonstrated for visual acuity after surgery for macular hole and macular pucker. Fifty-nine consecutive patients underwent pars plana vitrectomy for macular pucker (n = 41) or full-thickness macular holes (n = 18). Functional assessment was made at 3, 6, and 12 months after surgery and included far visual acuity (Early Treatment Diabetic Retinopathy Study charts), retinal sensitivity using the microperimeter (MP1, Nidek Technologies, Padova, Italy), and reading ability (MNRead charts). An improvement was recorded both for macular holes and puckers not only for visual acuity, but also for reading acuity and mean central retinal sensitivity (P < 0.01 for the overall comparisons between baseline and follow-up values). Maximum reading speed was already good at baseline both for puckers and holes overall, and a significant mean improvement was recorded only in patients with macular hole at 6 and 12 months (P < 0.01). Although eyes with macular holes had worse baseline visual function compared with puckers (P < 0.01 for all measures of visual function except for reading speed), they recovered to similar levels thanks to greater improvement (P < 0.05 for the difference in improvement during follow-up between puckers and holes for all measures of visual function). No differences were found among indocyanine green or trypan blue staining compared with no staining for internal limiting membrane removal based on all outcome measures (P > 0.05 for the overall difference of visual function improvement during follow-up). The improvement found for visual acuity after vitrectomy for macular hole and pucker also regards retinal sensitivity and reading ability for up to 12 months. This is reassuring concerning the benefits for the patients, and this shows that visual acuity is a valid functional measure for investigating the efficacy of macular surgery.

Functional and visual acuity outcomes of cataract surgery in Timor-Leste (East Timor).

PubMed

Naidu, Girish; Correia, Marcelino; Nirmalan, Praveen; Verma, Nitin; Thomas, Ravi

2014-12-01

To report functional outcomes following cataract surgery in Timor-Leste. Pre- and post-intervention study measuring visual function improvement following cataract surgery. Presenting visual acuity (VA) was measured and visual function documented using the Indian vision function questionnaire (IND-VFQ). All 174 persons undergoing cataract surgery from November 2009 to January 2011 in Timor-Leste were included. Mean age was 65.4 years; 113 (64.9%) were male, 143 (82.1%) were from a rural background and 151 (86.8%) were illiterate. Pre-operatively, 77 of 174 patients (44.3%, 95% confidence interval, CI, 37.0-51.7%) were blind (VA ≤3/60), 77 (44.3%, 95% CI 37.0-51.7%) were visually impaired (VA <6/18->3/60), while 20 (11.5%, 95% CI 7.4-16.9%) had presenting acuity ≥6/18 in the better eye. Following surgery, significant improvement in visual function was demonstrated by an effect size of 2.8, 3.7 and 3.9 in the domains of general functioning, psychosocial impact and visual symptoms, respectively. Four weeks following surgery, 85 patients (48.9%, 95% CI 41.5-66.3%) had a presenting VA ≥6/18, 74 (42.5%, 95% CI 35.3-45.9%) were visually impaired and 15 (8.6%, 95% CI 5.0-13.6%) were blind. IND-VFQ improvement occurred even in patients remaining visually impaired or blind following surgery. In this setting, cataract surgery led to a significant improvement in visual function but the VA results did not meet World Health Organization quality criteria. IND-VFQ results, although complementary to clinical VA outcomes did not, in isolation, reflect the need to improve program quality.

Donor and host photoreceptors engage in material transfer following transplantation of post-mitotic photoreceptor precursors

PubMed Central

Pearson, R. A.; Gonzalez-Cordero, A.; West, E. L.; Ribeiro, J. R.; Aghaizu, N.; Goh, D.; Sampson, R. D.; Georgiadis, A.; Waldron, P. V.; Duran, Y.; Naeem, A.; Kloc, M.; Cristante, E.; Kruczek, K.; Warre-Cornish, K.; Sowden, J. C.; Smith, A. J.; Ali, R. R.

2016-01-01

Photoreceptor replacement by transplantation is proposed as a treatment for blindness. Transplantation of healthy photoreceptor precursor cells into diseased murine eyes leads to the presence of functional photoreceptors within host retinae that express an array of donor-specific proteins. The resulting improvement in visual function was understood to be due to donor cells integrating within host retinae. Here, however, we show that while integration occurs the majority of donor-reporter-labelled cells in the host arises as a result of material transfer between donor and host photoreceptors. Material transfer does not involve permanent donor–host nuclear or cell–cell fusion, or the uptake of free protein or nucleic acid from the extracellular environment. Instead, RNA and/or protein are exchanged between donor and host cells in vivo. These data require a re-evaluation of the mechanisms underlying rescue by photoreceptor transplantation and raise the possibility of material transfer as a strategy for the treatment of retinal disorders. PMID:27701378

cis Retinol oxidation regulates photoreceptor access to the retina visual cycle and cone pigment regeneration

PubMed Central

Sato, Shinya

2016-01-01

Key points This study explores the nature of the cis retinol that Müller cells in the retina provide to cones for the regeneration of their visual pigment.We report that the retina visual cycle provides cones exclusively with 11‐cis chromophore in both salamander and mouse and show that this selectivity is dependent on the 11‐cis‐specific cellular retinaldehyde binding protein (CRALBP) present in Müller cells.Even though salamander blue cones and green rods share the same visual pigment, only blue cones but not green rods are able to dark‐adapt in the retina following a bleach and to use exogenous 9‐cis retinol for pigment regeneration, suggesting that access to the retina visual cycle is cone‐specific and pigment‐independent.Our results show that the retina produces 11‐cis retinol that can be oxidized and used for pigment regeneration and dark adaptation selectively in cones and not in rods. Abstract Chromophore supply by the retinal Müller cells (retina visual cycle) supports the efficient pigment regeneration required for cone photoreceptor function in bright light. Surprisingly, a large fraction of the chromophore produced by dihydroceramide desaturase‐1, the putative all‐trans retinol isomerase in Müller cells, appears to be 9‐cis retinol. In contrast, the canonical retinal pigment epithelium (RPE) visual cycle produces exclusively 11‐cis retinal. Here, we used the different absorption spectra of 9‐cis and 11‐cis pigments to identify the isoform of the chromophore produced by the visual cycle of the intact retina. We found that the spectral sensitivity of salamander and mouse cones dark‐adapted in the isolated retina (with only the retina visual cycle) was similar to that of cones dark‐adapted in the intact eye (with both the RPE and retina visual cycles) and consistent with pure 11‐cis pigment composition. However, in mice lacking the cellular retinaldehyde binding protein (CRALBP), cone spectral sensitivity contained a substantial 9‐cis component. Thus, the retina visual cycle provides cones exclusively with 11‐cis chromophore and this process is mediated by the 11‐cis selective CRALBP in Müller cells. Finally, despite sharing the same pigment, salamander blue cones, but not green rods, recovered their sensitivity in the isolated retina. Exogenous 9‐cis retinol produced robust sensitivity recovery in bleached red and blue cones but not in red and green rods, suggesting that cis retinol oxidation restricts access to the retina visual cycle to cones. PMID:27385534

Neuronal activity in the lateral cerebellum of the cat related to visual stimuli at rest, visually guided step modification, and saccadic eye movements

PubMed Central

Marple-Horvat, D E; Criado, J M; Armstrong, D M

1998-01-01

The discharge patterns of 166 lateral cerebellar neurones were studied in cats at rest and during visually guided stepping on a horizontal circular ladder. A hundred and twelve cells were tested against one or both of two visual stimuli: a brief full-field flash of light delivered during eating or rest, and a rung which moved up as the cat approached. Forty-five cells (40%) gave a short latency response to one or both of these stimuli. These visually responsive neurones were found in hemispheral cortex (rather than paravermal) and the lateral cerebellar nucleus (rather than nucleus interpositus).Thirty-seven cells (of 103 tested, 36%) responded to flash. The cortical visual response (mean onset latency 38 ms) was usually an increase in Purkinje cell discharge rate, of around 50 impulses s−1 and representing 1 or 2 additional spikes per trial (1.6 on average). The nuclear response to flash (mean onset latency 27 ms) was usually an increased discharge rate which was shorter lived and converted rapidly to a depression of discharge or return to control levels, so that there were on average only an additional 0.6 spikes per trial. A straightforward explanation of the difference between the cortical and nuclear response would be that the increased inhibitory Purkinje cell output cuts short the nuclear response.A higher proportion of cells responded to rung movement, sixteen of twenty-five tested (64%). Again most responded with increased discharge, which had longer latency than the flash response (first change in dentate output ca 60 ms after start of movement) and longer duration. Peak frequency changes were twice the size of those in response to flash, at 100 impulses s−1 on average and additional spikes per trial were correspondingly 3–4 times higher. Both cortical and nuclear responses were context dependent, being larger when the rung moved when the cat was closer than further away.A quarter of cells (20 of 84 tested, 24%) modulated their activity in advance of saccades, increasing their discharge rate. Four-fifths of these were non-reciprocally directionally selective. Saccade-related neurones were usually susceptible to other influences, i.e. their activity was not wholly explicable in terms of saccade parameters.Substantial numbers of visually responsive neurones also discharged in relation to stepping movements while other visually responsive neurones discharged in advance of saccadic eye movements. And more than half the cells tested were active in relation both to eye movements and to stepping movements. These combinations of properties qualify even individual cerebellar neurones to participate in the co-ordination of visually guided eye and limb movements. PMID:9490874

Intracellular pathways and nuclear localization signal peptide-mediated gene transfection by cationic polymeric nanovectors.

PubMed

Hu, Qinglian; Wang, Jinlei; Shen, Jie; Liu, Min; Jin, Xue; Tang, Guping; Chu, Paul K

2012-02-01

Polyethylenimine (PEI) - based polymers are promising cationic nanovectors. A good understanding of the mechanism by which cationic polymers/DNA complexes are internalized and delivered to nuclei helps to identify which transport steps may be manipulated in order to improve the transfection efficiency. In this work, cell internalization and trafficking of PEI-CyD (PC) composed of β-cyclodextrin (β-CyD) and polyethylenimine (PEI, Mw 600) are studied. The results show that the PC transfected DNA is internalized by binding membrane-associated proteoglycans. The endocytic pathway of the PC particles is caveolae- and clathrin-dependent with both pathways converging to the lysosome. The intracellular fate of the PC provides visual evidence that it can escape from the lysosome. Lysosomal inhibition with chloroquine has no effect on PC mediated transfection implying that blocking the lysosomal traffic does not improve transfection. To improve the nuclear delivery of PC transfected DNA, nuclear localization signal (NLS) peptides are chosen to conjugate and combine with the PC. Compared to PC/pDNA, PC-NLS/pDNA, and PC/pDNA/NLS can effectively improve gene transfection in dividing and non-dividing cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Five-Year PROSE Treatment for Aniridic Keratopathy.

PubMed

Kojima, Takashi; Hasegawa, Asato; Nakamura, Tomoaki; Isogai, Naoki; Kataoka, Takahiro; Ichikawa, Kazuo

2016-10-01

Aniridic keratopathy is vision-threatening condition in patients with aniridia. The keratopathy occurs due to limbal stem cell deficiency. When conventional treatments fail, surgical treatments such as corneal limbal transplantation or cultivated oral mucosal epithelium transplantation are the alternatives. Here, we report our experience with the management and monitoring of the progress of a case with aniridic keratopathy treated with a scleral lens. We describe the case of a 30-year-old woman with aniridic keratopathy in both eyes. She visited our outpatient clinic for treatment of visual disturbances in her left eye, which showed a 360° invasion of the conjunctiva. Despite conventional treatment with artificial tears and autologous serum eye drops, the left eye started to suffer from recurrent corneal erosions at 19 months after the initial visit. At 50 months after the initial visit, it presented with persistent epithelial defects and decrease in vision because of the invasion of the vascularized conjunctiva with subepithelial fibrosis. Upon concluding that conventional treatment was ineffective, we tried using a scleral lens (Prosthetic Replacement of the Ocular Surface Ecosystem; PROSE). After the scleral lens treatment, the epithelial defect quickly healed, and visual acuity improved. Six years after the initial visit, the patient's right eye also started to show epithelial irregularities, which were also treated with a scleral lens. The visual acuity in the right eye too recovered, and corneal transparency was maintained until 3 years after the scleral lens treatment. The current case showed that long-term scleral lens treatment is a promising option to maintain a healthy ocular surface and visual function in eyes with aniridia caused by limbal stem cell deficiency. Early treatment with a scleral lens may be beneficial in preventing stromal scar formation in the cornea affected by aniridic keratopathy.

Methane attenuates retinal ischemia/reperfusion injury via anti-oxidative and anti-apoptotic pathways.

PubMed

Liu, Lin; Sun, Qinglei; Wang, Ruobing; Chen, Zeli; Wu, Jiangchun; Xia, Fangzhou; Fan, Xian-Qun

2016-09-01

Retinal ischemia/reperfusion injury (IRI) may cause incurable visual impairment due to neural regeneration limits. Methane was shown to exert a protective effect against IRI in many organs. This study aims to explore the possible protective effects of methane-rich saline against retinal IRI in rat. Retinal IRI was performed on the right eyes of male Sprague-Dawley rats, which were immediately injected intraperitoneally with methane-saturated saline (25ml/kg). At one week after surgery, the number of retinal ganglion cells (RGCs), total retinal thickness, visual function were measured by hematoxylin and eosin staining, FluoroGold anterograde labeling and flash visual evoked potentials. The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-Hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), caspase-3, caspase-9, B cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in retinas were assessed by immunofluorescence staining, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. As expected, methane treatment significantly improved the retinal IRI-induced RGC loss, total retinal layer thinning and visual dysfunction. Moreover, methane treatment significantly reduced the levels of oxidative stress biomarkers (8-OHdG, 4-HNE, MDA) and increased the antioxidant enzyme activities (SOD, CAT, GPx) in the retinas with IRI. Meanwhile, methane treatment significantly increased the anti-apoptotic gene (Bcl-2) expression and decreased the pro-apoptotic gene (Bax) expression, accompanied by the suppression of caspase-3 and caspase-9 activity. Thus, these data demonstrated that methane can exert a neuroprotective role against retinal IRI through anti-oxidative and anti-apoptotic pathways. Copyright © 2016. Published by Elsevier B.V.

Visual-servoing optical microscopy

DOEpatents

Callahan, Daniel E.; Parvin, Bahram

2009-06-09

The present invention provides methods and devices for the knowledge-based discovery and optimization of differences between cell types. In particular, the present invention provides visual servoing optical microscopy, as well as analysis methods. The present invention provides means for the close monitoring of hundreds of individual, living cells over time: quantification of dynamic physiological responses in multiple channels; real-time digital image segmentation and analysis; intelligent, repetitive computer-applied cell stress and cell stimulation; and the ability to return to the same field of cells for long-term studies and observation. The present invention further provides means to optimize culture conditions for specific subpopulations of cells.

Visual-servoing optical microscopy

DOEpatents

Callahan, Daniel E [Martinez, CA; Parvin, Bahram [Mill Valley, CA

2011-05-24

The present invention provides methods and devices for the knowledge-based discovery and optimization of differences between cell types. In particular, the present invention provides visual servoing optical microscopy, as well as analysis methods. The present invention provides means for the close monitoring of hundreds of individual, living cells over time; quantification of dynamic physiological responses in multiple channels; real-time digital image segmentation and analysis; intelligent, repetitive computer-applied cell stress and cell stimulation; and the ability to return to the same field of cells for long-term studies and observation. The present invention further provides means to optimize culture conditions for specific subpopulations of cells.

Visual-servoing optical microscopy

DOEpatents

Callahan, Daniel E; Parvin, Bahram

2013-10-01

The present invention provides methods and devices for the knowledge-based discovery and optimization of differences between cell types. In particular, the present invention provides visual servoing optical microscopy, as well as analysis methods. The present invention provides means for the close monitoring of hundreds of individual, living cells over time; quantification of dynamic physiological responses in multiple channels; real-time digital image segmentation and analysis; intelligent, repetitive computer-applied cell stress and cell stimulation; and the ability to return to the same field of cells for long-term studies and observation. The present invention further provides means to optimize culture conditions for specific subpopulations of cells.

Photon Hunting in the Twilight Zone: Visual Features of Mesopelagic Bioluminescent Sharks

PubMed Central

Claes, Julien M.; Partridge, Julian C.; Hart, Nathan S.; Garza-Gisholt, Eduardo; Ho, Hsuan-Ching; Mallefet, Jérôme; Collin, Shaun P.

2014-01-01

The mesopelagic zone is a visual scene continuum in which organisms have developed various strategies to optimize photon capture. Here, we used light microscopy, stereology-assisted retinal topographic mapping, spectrophotometry and microspectrophotometry to investigate the visual ecology of deep-sea bioluminescent sharks [four etmopterid species (Etmopterus lucifer, E. splendidus, E. spinax and Trigonognathus kabeyai) and one dalatiid species (Squaliolus aliae)]. We highlighted a novel structure, a translucent area present in the upper eye orbit of Etmopteridae, which might be part of a reference system for counterillumination adjustment or acts as a spectral filter for camouflage breaking, as well as several ocular specialisations such as aphakic gaps and semicircular tapeta previously unknown in elasmobranchs. All species showed pure rod hexagonal mosaics with a high topographic diversity. Retinal specialisations, formed by shallow cell density gradients, may aid in prey detection and reflect lifestyle differences; pelagic species display areae centrales while benthopelagic and benthic species display wide and narrow horizontal streaks, respectively. One species (E. lucifer) displays two areae within its horizontal streak that likely allows detection of conspecifics' elongated bioluminescent flank markings. Ganglion cell topography reveals less variation with all species showing a temporal area for acute frontal binocular vision. This area is dorsally extended in T. kabeyai, allowing this species to adjust the strike of its peculiar jaws in the ventro-frontal visual field. Etmopterus lucifer showed an additional nasal area matching a high rod density area. Peak spectral sensitivities of the rod visual pigments (λmax) fall within the range 484–491 nm, allowing these sharks to detect a high proportion of photons present in their habitat. Comparisons with previously published data reveal ocular differences between bioluminescent and non-bioluminescent deep-sea sharks. In particular, bioluminescent sharks possess higher rod densities, which might provide them with improved temporal resolution particularly useful for bioluminescent communication during social interactions. PMID:25099504

Photon hunting in the twilight zone: visual features of mesopelagic bioluminescent sharks.

PubMed

Claes, Julien M; Partridge, Julian C; Hart, Nathan S; Garza-Gisholt, Eduardo; Ho, Hsuan-Ching; Mallefet, Jérôme; Collin, Shaun P

2014-01-01

The mesopelagic zone is a visual scene continuum in which organisms have developed various strategies to optimize photon capture. Here, we used light microscopy, stereology-assisted retinal topographic mapping, spectrophotometry and microspectrophotometry to investigate the visual ecology of deep-sea bioluminescent sharks [four etmopterid species (Etmopterus lucifer, E. splendidus, E. spinax and Trigonognathus kabeyai) and one dalatiid species (Squaliolus aliae)]. We highlighted a novel structure, a translucent area present in the upper eye orbit of Etmopteridae, which might be part of a reference system for counterillumination adjustment or acts as a spectral filter for camouflage breaking, as well as several ocular specialisations such as aphakic gaps and semicircular tapeta previously unknown in elasmobranchs. All species showed pure rod hexagonal mosaics with a high topographic diversity. Retinal specialisations, formed by shallow cell density gradients, may aid in prey detection and reflect lifestyle differences; pelagic species display areae centrales while benthopelagic and benthic species display wide and narrow horizontal streaks, respectively. One species (E. lucifer) displays two areae within its horizontal streak that likely allows detection of conspecifics' elongated bioluminescent flank markings. Ganglion cell topography reveals less variation with all species showing a temporal area for acute frontal binocular vision. This area is dorsally extended in T. kabeyai, allowing this species to adjust the strike of its peculiar jaws in the ventro-frontal visual field. Etmopterus lucifer showed an additional nasal area matching a high rod density area. Peak spectral sensitivities of the rod visual pigments (λmax) fall within the range 484-491 nm, allowing these sharks to detect a high proportion of photons present in their habitat. Comparisons with previously published data reveal ocular differences between bioluminescent and non-bioluminescent deep-sea sharks. In particular, bioluminescent sharks possess higher rod densities, which might provide them with improved temporal resolution particularly useful for bioluminescent communication during social interactions.

In-vivo expansion of autologous limbal stem cell using simple limbal epithelial transplantation for treatment of limbal stem cell deficiency

PubMed Central

Lal, Ikeda; Panchal, Bhavik Uttam; Basu, Sayan; Sangwan, Virender S

2013-01-01

A 20-year-old man from Bangladesh suffered accidental alkali injury to his right eye in May 2010 leading to total limbal stem cell deficiency. An amniotic membrane graft was performed 5 days after the accident and the patient presented to our institute 6 months later. On ocular examination, his best corrected visual acuity (BCVA) was 20/50 with a 360° pannus at the periphery and central area was spared but had stromal scarring. He underwent simple limbal epithelial transplantation (SLET) taking a limbal biopsy from his left eye and was prescribed steroid and antibiotic eye drops postoperatively as per the standard regimen. At 2 year follow-up, the patient's ocular surface is stable with improvement in  BCVA to 20/25 post-SLET. PMID:23704435

Cognitive and psychological science insights to improve climate change data visualization

NASA Astrophysics Data System (ADS)

Harold, Jordan; Lorenzoni, Irene; Shipley, Thomas F.; Coventry, Kenny R.

2016-12-01

Visualization of climate data plays an integral role in the communication of climate change findings to both expert and non-expert audiences. The cognitive and psychological sciences can provide valuable insights into how to improve visualization of climate data based on knowledge of how the human brain processes visual and linguistic information. We review four key research areas to demonstrate their potential to make data more accessible to diverse audiences: directing visual attention, visual complexity, making inferences from visuals, and the mapping between visuals and language. We present evidence-informed guidelines to help climate scientists increase the accessibility of graphics to non-experts, and illustrate how the guidelines can work in practice in the context of Intergovernmental Panel on Climate Change graphics.

Real-time Visualization of Tissue Dynamics during Embryonic Development and Malignant Transformation

NASA Astrophysics Data System (ADS)

Yamada, Kenneth

Tissues undergo dramatic changes in organization during embryonic development, as well as during cancer progression and invasion. Recent advances in microscopy now allow us to visualize and track directly the dynamic movements of tissues, their constituent cells, and cellular substructures. This behavior can now be visualized not only in regular tissue culture on flat surfaces (`2D' environments), but also in a variety of 3D environments that may provide physiological cues relevant to understanding dynamics within living organisms. Acquisition of imaging data using various microscopy modalities will provide rich opportunities for determining the roles of physical factors and for computational modeling of complex processes in living tissues. Direct visualization of real-time motility is providing insight into biology spanning multiple spatio-temporal scales. Many cells in our body are known to be in contact with connective tissue and other forms of extracellular matrix. They do so through microscopic cellular adhesions that bind to matrix proteins. In particular, fluorescence microscopy has revealed that cells dynamically probe and bend the matrix at the sites of cell adhesions, and that 3D matrix architecture, stiffness, and elasticity can each regulate migration of the cells. Conversely, cells remodel their local matrix as organs form or tumors invade. Cancer cells can invade tissues using microscopic protrusions that degrade the surrounding matrix; in this case, the local matrix protein concentration is more important for inducing the micro-invasive protrusions than stiffness. On the length scales of tissues, transiently high rates of individual cell movement appear to help establish organ architecture. In fact, isolated cells can self-organize to form tissue structures. In all of these cases, in-depth real-time visualization will ultimately provide the extensive data needed for computer modeling and for testing hypotheses in which physical forces interact closely with cell signaling to form organs or promote tumor invasion.

Dissection of Drosophila Visual Circuits Implicative in Figure Motion

NASA Astrophysics Data System (ADS)

Kelley, Ross G.

The Drosophila visual system offers a model to study the foundations of how motion signals are computed from raw visual input and transformed into behavioral output. My studies focus on how specific cells in the Drosophila nervous system implement this input-output transformation. The individual cell types are known from classical studies using Golgi impregnations, but the assembly of motion processing circuits and the behavioral outputs remain poorly understood. Using an electronic flight simulator for flies and a white-noise analysis developed by Aptekar et al., I screen specific neurons in the optic lobes for behavioral ramifications. This approach produces wing responses to both the spatial and temporal dynamics of motion signals. The results of these experiments give Spatiotemporal Action Fields (STAFs) across the entire visual panorama. Genetically inactivating a distinct grouping of cells in the third optic ganglion, the Lobula Plate, the Horizontal System (HS) cell group, produced a robust phenotype through STAF analysis. Using the Gal4-UAS transgene expression system, we selectively inactivated the HS cells by expressing in their membrane inward rectifying potassium channels (Kir2.1) to hyperpolarize these cells, preventing their role in synaptic signaling. The results of the experiments show mutants lose steering responses to several distinct categories of figure motion and reduced behavioral responses to figure motion set against a contrasting moving background, highlighting their role in figure tracking behavior. Finally, a synapse inactivating protein, tetanus toxin (TNT), expressed in the HS cell group, produces a different behavioral phenotype than overexpressing inward rectifier. TNT, a bacterial neurotoxin, cleaves SNARE proteins resulting in loss of synaptic output of the cell, but the dendrites are intact and signal normally, preserving dendro-dendritic interactions known to sculpt the visual receptive fields of these cells. The two distinct phenotypes to each genetically targeted silencer differentiate the functional role of dendritic integration versus axonal output in this important cell group.

Visualization of glucagon secretion from pancreatic α cells by bioluminescence video microscopy: Identification of secretion sites in the intercellular contact regions

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

Yokawa, Satoru; School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650; Suzuki, Takahiro

We have firstly visualized glucagon secretion using a method of video-rate bioluminescence imaging. The fusion protein of proglucagon and Gaussia luciferase (PGCG-GLase) was used as a reporter to detect glucagon secretion and was efficiently expressed in mouse pancreatic α cells (αTC1.6) using a preferred human codon-optimized gene. In the culture medium of the cells expressing PGCG-GLase, luminescence activity determined with a luminometer was increased with low glucose stimulation and KCl-induced depolarization, as observed for glucagon secretion. From immunochemical analyses, PGCG-GLase stably expressed in clonal αTC1.6 cells was correctly processed and released by secretory granules. Luminescence signals of the secreted PGCG-GLase frommore » the stable cells were visualized by video-rate bioluminescence microscopy. The video images showed an increase in glucagon secretion from clustered cells in response to stimulation by KCl. The secretory events were observed frequently at the intercellular contact regions. Thus, the localization and frequency of glucagon secretion might be regulated by cell-cell adhesion. - Highlights: • The fused protein of proglucagon to Gaussia luciferase was used as a reporter. • The fusion protein was highly expressed using a preferred human-codon optimized gene. • Glucagon secretion stimulated by depolarization was determined by luminescence. • Glucagon secretion in α cells was visualized by bioluminescence imaging. • Glucagon secretion sites were localized in the intercellular contact regions.« less

Properties of V1 Neurons Tuned to Conjunctions of Visual Features: Application of the V1 Saliency Hypothesis to Visual Search behavior

PubMed Central

Zhaoping, Li; Zhe, Li

2012-01-01

From a computational theory of V1, we formulate an optimization problem to investigate neural properties in the primary visual cortex (V1) from human reaction times (RTs) in visual search. The theory is the V1 saliency hypothesis that the bottom-up saliency of any visual location is represented by the highest V1 response to it relative to the background responses. The neural properties probed are those associated with the less known V1 neurons tuned simultaneously or conjunctively in two feature dimensions. The visual search is to find a target bar unique in color (C), orientation (O), motion direction (M), or redundantly in combinations of these features (e.g., CO, MO, or CM) among uniform background bars. A feature singleton target is salient because its evoked V1 response largely escapes the iso-feature suppression on responses to the background bars. The responses of the conjunctively tuned cells are manifested in the shortening of the RT for a redundant feature target (e.g., a CO target) from that predicted by a race between the RTs for the two corresponding single feature targets (e.g., C and O targets). Our investigation enables the following testable predictions. Contextual suppression on the response of a CO-tuned or MO-tuned conjunctive cell is weaker when the contextual inputs differ from the direct inputs in both feature dimensions, rather than just one. Additionally, CO-tuned cells and MO-tuned cells are often more active than the single feature tuned cells in response to the redundant feature targets, and this occurs more frequently for the MO-tuned cells such that the MO-tuned cells are no less likely than either the M-tuned or O-tuned neurons to be the most responsive neuron to dictate saliency for an MO target. PMID:22719829

Properties of V1 neurons tuned to conjunctions of visual features: application of the V1 saliency hypothesis to visual search behavior.

PubMed

Zhaoping, Li; Zhe, Li

2012-01-01

From a computational theory of V1, we formulate an optimization problem to investigate neural properties in the primary visual cortex (V1) from human reaction times (RTs) in visual search. The theory is the V1 saliency hypothesis that the bottom-up saliency of any visual location is represented by the highest V1 response to it relative to the background responses. The neural properties probed are those associated with the less known V1 neurons tuned simultaneously or conjunctively in two feature dimensions. The visual search is to find a target bar unique in color (C), orientation (O), motion direction (M), or redundantly in combinations of these features (e.g., CO, MO, or CM) among uniform background bars. A feature singleton target is salient because its evoked V1 response largely escapes the iso-feature suppression on responses to the background bars. The responses of the conjunctively tuned cells are manifested in the shortening of the RT for a redundant feature target (e.g., a CO target) from that predicted by a race between the RTs for the two corresponding single feature targets (e.g., C and O targets). Our investigation enables the following testable predictions. Contextual suppression on the response of a CO-tuned or MO-tuned conjunctive cell is weaker when the contextual inputs differ from the direct inputs in both feature dimensions, rather than just one. Additionally, CO-tuned cells and MO-tuned cells are often more active than the single feature tuned cells in response to the redundant feature targets, and this occurs more frequently for the MO-tuned cells such that the MO-tuned cells are no less likely than either the M-tuned or O-tuned neurons to be the most responsive neuron to dictate saliency for an MO target.

Bimolecular fluorescence complementation: visualization of molecular interactions in living cells.

PubMed

Kerppola, Tom K

2008-01-01

A variety of experimental methods have been developed for the analysis of protein interactions. The majority of these methods either require disruption of the cells to detect molecular interactions or rely on indirect detection of the protein interaction. The bimolecular fluorescence complementation (BiFC) assay provides a direct approach for the visualization of molecular interactions in living cells and organisms. The BiFC approach is based on the facilitated association between two fragments of a fluorescent protein when the fragments are brought together by an interaction between proteins fused to the fragments. The BiFC approach has been used for visualization of interactions among a variety of structurally diverse interaction partners in many different cell types. It enables detection of transient complexes as well as complexes formed by a subpopulation of the interaction partners. It is essential to include negative controls in each experiment in which the interface between the interaction partners has been mutated or deleted. The BiFC assay has been adapted for simultaneous visualization of multiple protein complexes in the same cell and the competition for shared interaction partners. A ubiquitin-mediated fluorescence complementation assay has also been developed for visualization of the covalent modification of proteins by ubiquitin family peptides. These fluorescence complementation assays have a great potential to illuminate a variety of biological interactions in the future.

Enhanced visual acuity and image perception following correction of highly aberrated eyes using an adaptive optics visual simulator.

PubMed

Rocha, Karolinne Maia; Vabre, Laurent; Chateau, Nicolas; Krueger, Ronald R

2010-01-01

To evaluate the changes in visual acuity and visual perception generated by correcting higher order aberrations in highly aberrated eyes using a large-stroke adaptive optics visual simulator. A crx1 Adaptive Optics Visual Simulator (Imagine Eyes) was used to correct and modify the wavefront aberrations in 12 keratoconic eyes and 8 symptomatic postoperative refractive surgery (LASIK) eyes. After measuring ocular aberrations, the device was programmed to compensate for the eye's wavefront error from the second order to the fifth order (6-mm pupil). Visual acuity was assessed through the adaptive optics system using computer-generated ETDRS opto-types and the Freiburg Visual Acuity and Contrast Test. Mean higher order aberration root-mean-square (RMS) errors in the keratoconus and symptomatic LASIK eyes were 1.88+/-0.99 microm and 1.62+/-0.79 microm (6-mm pupil), respectively. The visual simulator correction of the higher order aberrations present in the keratoconus eyes improved their visual acuity by a mean of 2 lines when compared to their best spherocylinder correction (mean decimal visual acuity with spherocylindrical correction was 0.31+/-0.18 and improved to 0.44+/-0.23 with higher order aberration correction). In the symptomatic LASIK eyes, the mean decimal visual acuity with spherocylindrical correction improved from 0.54+/-0.16 to 0.71+/-0.13 with higher order aberration correction. The visual perception of ETDRS letters was improved when correcting higher order aberrations. The adaptive optics visual simulator can effectively measure and compensate for higher order aberrations (second to fifth order), which are associated with diminished visual acuity and perception in highly aberrated eyes. The adaptive optics technology may be of clinical benefit when counseling patients with highly aberrated eyes regarding their maximum subjective potential for vision correction. Copyright 2010, SLACK Incorporated.

Improving Dorsal Stream Function in Dyslexics by Training Figure/Ground Motion Discrimination Improves Attention, Reading Fluency, and Working Memory

PubMed Central

Lawton, Teri

2016-01-01

There is an ongoing debate about whether the cause of dyslexia is based on linguistic, auditory, or visual timing deficits. To investigate this issue three interventions were compared in 58 dyslexics in second grade (7 years on average), two targeting the temporal dynamics (timing) of either the auditory or visual pathways with a third reading intervention (control group) targeting linguistic word building. Visual pathway training in dyslexics to improve direction-discrimination of moving test patterns relative to a stationary background (figure/ground discrimination) significantly improved attention, reading fluency, both speed and comprehension, phonological processing, and both auditory and visual working memory relative to controls, whereas auditory training to improve phonological processing did not improve these academic skills significantly more than found for controls. This study supports the hypothesis that faulty timing in synchronizing the activity of magnocellular with parvocellular visual pathways is a fundamental cause of dyslexia, and argues against the assumption that reading deficiencies in dyslexia are caused by phonological deficits. This study demonstrates that visual movement direction-discrimination can be used to not only detect dyslexia early, but also for its successful treatment, so that reading problems do not prevent children from readily learning. PMID:27551263

Subthalamic nucleus stimulation selectively improves motor and visual memory performance in Parkinson's disease.

PubMed

Mollion, Hélène; Dominey, Peter Ford; Broussolle, Emmanuel; Ventre-Dominey, Jocelyne

2011-09-01

Although the treatment of Parkinson's disease via subthalamic stimulation yields remarkable improvements in motor symptoms, its effects on memory function are less clear. In this context, we previously demonstrated dissociable effects of levodopa therapy on parkinsonian performance in spatial and nonspatial visual working memory. Here we used the same protocol with an additional, purely motor task to investigate visual memory and motor performance in 2 groups of patients with Parkinson's disease with or without subthalamic stimulation. In each stimulation condition, subjects performed a simple motor task and 3 successive cognitive tasks: 1 conditional color-response association task and 2 visual (spatial and nonspatial) working memory tasks. The Parkinson's groups were compared with a control group of age-matched healthy subjects. Our principal results demonstrated that (1) in the motor task, stimulated patients were significantly improved with respect to nonstimulated patients and did not differ significantly from healthy controls, and (2) in the cognitive tasks, stimulated patients were significantly improved with respect to nonstimulated patients, but both remained significantly impaired when compared with healthy controls. These results demonstrate selective effects of subthalamic stimulation on parkinsonian disorders of motor and visual memory functions, with clear motor improvement for stimulated patients and a partial improvement for their visual memory processing. Copyright © 2011 Movement Disorder Society.

Retinal specialization through spatially varying cell densities and opsin coexpression in cichlid fish.

PubMed

Dalton, Brian E; de Busserolles, Fanny; Marshall, N Justin; Carleton, Karen L

2017-01-15

The distinct behaviours of animals and the varied habitats in which animals live place different requirements on their visual systems. A trade-off exists between resolution and sensitivity, with these properties varying across the retina. Spectral sensitivity, which affects both achromatic and chromatic (colour) vision, also varies across the retina, though the function of this inhomogeneity is less clear. We previously demonstrated spatially varying spectral sensitivity of double cones in the cichlid fish Metriaclima zebra owing to coexpression of different opsins. Here, we map the distributions of ganglion cells and cone cells and quantify opsin coexpression in single cones to show these also vary across the retina. We identify an area centralis with peak acuity and infrequent coexpression, which may be suited for tasks such as foraging and detecting male signals. The peripheral retina has reduced ganglion cell densities and increased opsin coexpression. Modeling of cichlid visual tasks indicates that coexpression might hinder colour discrimination of foraging targets and some fish colours. But, coexpression might improve contrast detection of dark objects against bright backgrounds, which might be useful for detecting predators or zooplankton. This suggests a trade-off between acuity and colour discrimination in the central retina versus lower resolution but more sensitive contrast detection in the peripheral retina. Significant variation in the pattern of coexpression among individuals, however, raises interesting questions about the selective forces at work. © 2017. Published by The Company of Biologists Ltd.

Range management visual impacts

Treesearch

Bruce R. Brown; David Kissel

1979-01-01

Historical overgrazing of western public rangelands has resulted in the passage of the Public Rangeland Improvement Act of 1978. The main purpose of this Act is to improve unsatisfactory range conditions. A contributing factor to unfavorable range conditions is adverse visual impacts. These visual impacts can be identified in three categories of range management: range...

Characterizing and Improving Spatial Visualization Skills

ERIC Educational Resources Information Center

Titus, Sarah; Horsman, Eric

2009-01-01

Three-dimensional spatial visualization is an essential skill for geoscientists. We conducted two evaluations of students' spatial skills to examine whether their skills improve after enrollment in a geology course or courses. First, we present results of pre- and post-course survey of abstract visualization skills used to characterize the range…

Attentional Modulation in Visual Cortex Is Modified during Perceptual Learning

ERIC Educational Resources Information Center

Bartolucci, Marco; Smith, Andrew T.

2011-01-01

Practicing a visual task commonly results in improved performance. Often the improvement does not transfer well to a new retinal location, suggesting that it is mediated by changes occurring in early visual cortex, and indeed neuroimaging and neurophysiological studies both demonstrate that perceptual learning is associated with altered activity…

Discovery learning model with geogebra assisted for improvement mathematical visual thinking ability

NASA Astrophysics Data System (ADS)

Juandi, D.; Priatna, N.

2018-05-01

The main goal of this study is to improve the mathematical visual thinking ability of high school student through implementation the Discovery Learning Model with Geogebra Assisted. This objective can be achieved through study used quasi-experimental method, with non-random pretest-posttest control design. The sample subject of this research consist of 62 senior school student grade XI in one of school in Bandung district. The required data will be collected through documentation, observation, written tests, interviews, daily journals, and student worksheets. The results of this study are: 1) Improvement students Mathematical Visual Thinking Ability who obtain learning with applied the Discovery Learning Model with Geogebra assisted is significantly higher than students who obtain conventional learning; 2) There is a difference in the improvement of students’ Mathematical Visual Thinking ability between groups based on prior knowledge mathematical abilities (high, medium, and low) who obtained the treatment. 3) The Mathematical Visual Thinking Ability improvement of the high group is significantly higher than in the medium and low groups. 4) The quality of improvement ability of high and low prior knowledge is moderate category, in while the quality of improvement ability in the high category achieved by student with medium prior knowledge.

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel.

PubMed

Bolgioni, Amanda F; Vittoria, Marc A; Ganem, Neil J

2018-05-14

Live-cell imaging is a powerful technique that can be used to directly visualize biological phenomena in single cells over extended periods of time. Over the past decade, new and innovative technologies have greatly enhanced the practicality of live-cell imaging. Cells can now be kept in focus and continuously imaged over several days while maintained under 37 °C and 5% CO2 cell culture conditions. Moreover, multiple fields of view representing different experimental conditions can be acquired simultaneously, thus providing high-throughput experimental data. Live-cell imaging provides a significant advantage over fixed-cell imaging by allowing for the direct visualization and temporal quantitation of dynamic cellular events. Live-cell imaging can also identify variation in the behavior of single cells that would otherwise have been missed using population-based assays. Here, we describe live-cell imaging protocols to assess cell fate decisions following treatment with the anti-mitotic drug paclitaxel. We demonstrate methods to visualize whether mitotically arrested cells die directly from mitosis or slip back into interphase. We also describe how the fluorescent ubiquitination-based cell cycle indicator (FUCCI) system can be used to assess the fraction of interphase cells born from mitotic slippage that are capable of re-entering the cell cycle. Finally, we describe a live-cell imaging method to identify nuclear envelope rupture events.

Training-induced recovery of low-level vision followed by mid-level perceptual improvements in developmental object and face agnosia

PubMed Central

Lev, Maria; Gilaie-Dotan, Sharon; Gotthilf-Nezri, Dana; Yehezkel, Oren; Brooks, Joseph L; Perry, Anat; Bentin, Shlomo; Bonneh, Yoram; Polat, Uri

2015-01-01

Long-term deprivation of normal visual inputs can cause perceptual impairments at various levels of visual function, from basic visual acuity deficits, through mid-level deficits such as contour integration and motion coherence, to high-level face and object agnosia. Yet it is unclear whether training during adulthood, at a post-developmental stage of the adult visual system, can overcome such developmental impairments. Here, we visually trained LG, a developmental object and face agnosic individual. Prior to training, at the age of 20, LG's basic and mid-level visual functions such as visual acuity, crowding effects, and contour integration were underdeveloped relative to normal adult vision, corresponding to or poorer than those of 5–6 year olds (Gilaie-Dotan, Perry, Bonneh, Malach & Bentin, 2009). Intensive visual training, based on lateral interactions, was applied for a period of 9 months. LG's directly trained but also untrained visual functions such as visual acuity, crowding, binocular stereopsis and also mid-level contour integration improved significantly and reached near-age-level performance, with long-term (over 4 years) persistence. Moreover, mid-level functions that were tested post-training were found to be normal in LG. Some possible subtle improvement was observed in LG's higher-order visual functions such as object recognition and part integration, while LG's face perception skills have not improved thus far. These results suggest that corrective training at a post-developmental stage, even in the adult visual system, can prove effective, and its enduring effects are the basis for a revival of a developmental cascade that can lead to reduced perceptual impairments. PMID:24698161

Training-induced recovery of low-level vision followed by mid-level perceptual improvements in developmental object and face agnosia.

PubMed

Lev, Maria; Gilaie-Dotan, Sharon; Gotthilf-Nezri, Dana; Yehezkel, Oren; Brooks, Joseph L; Perry, Anat; Bentin, Shlomo; Bonneh, Yoram; Polat, Uri

2015-01-01

Long-term deprivation of normal visual inputs can cause perceptual impairments at various levels of visual function, from basic visual acuity deficits, through mid-level deficits such as contour integration and motion coherence, to high-level face and object agnosia. Yet it is unclear whether training during adulthood, at a post-developmental stage of the adult visual system, can overcome such developmental impairments. Here, we visually trained LG, a developmental object and face agnosic individual. Prior to training, at the age of 20, LG's basic and mid-level visual functions such as visual acuity, crowding effects, and contour integration were underdeveloped relative to normal adult vision, corresponding to or poorer than those of 5-6 year olds (Gilaie-Dotan, Perry, Bonneh, Malach & Bentin, 2009). Intensive visual training, based on lateral interactions, was applied for a period of 9 months. LG's directly trained but also untrained visual functions such as visual acuity, crowding, binocular stereopsis and also mid-level contour integration improved significantly and reached near-age-level performance, with long-term (over 4 years) persistence. Moreover, mid-level functions that were tested post-training were found to be normal in LG. Some possible subtle improvement was observed in LG's higher-order visual functions such as object recognition and part integration, while LG's face perception skills have not improved thus far. These results suggest that corrective training at a post-developmental stage, even in the adult visual system, can prove effective, and its enduring effects are the basis for a revival of a developmental cascade that can lead to reduced perceptual impairments. © 2014 The Authors. Developmental Science Published by John Wiley & Sons Ltd.

An egalitarian network model for the emergence of simple and complex cells in visual cortex

PubMed Central

Tao, Louis; Shelley, Michael; McLaughlin, David; Shapley, Robert

2004-01-01

We explain how simple and complex cells arise in a large-scale neuronal network model of the primary visual cortex of the macaque. Our model consists of ≈4,000 integrate-and-fire, conductance-based point neurons, representing the cells in a small, 1-mm2 patch of an input layer of the primary visual cortex. In the model the local connections are isotropic and nonspecific, and convergent input from the lateral geniculate nucleus confers cortical cells with orientation and spatial phase preference. The balance between lateral connections and lateral geniculate nucleus drive determines whether individual neurons in this recurrent circuit are simple or complex. The model reproduces qualitatively the experimentally observed distributions of both extracellular and intracellular measures of simple and complex response. PMID:14695891

Shifting attention across near and far spaces: implications for the use of hands-free cell phones while driving.

PubMed

Ferlazzo, Fabio; Fagioli, Sabrina; Di Nocera, Francesco; Sdoia, Stefano

2008-11-01

In three experiments, participants performed two tasks concurrently during driving. In the peripheral detection task, they responded manually to visual stimuli delivered through a LED placed on the internal rear mirror; in the conversation task, they were engaged in a conversation with a passenger, or through earphone-operated, loudspeaker-operated, or hand-held cell phones. Results showed that drivers were slower at responding to the visual stimuli when conversing through a hand-held cell phone or an earphone-operated cell phone than when conversing through a loudspeaker-operated cell phone or with a passenger. These results suggest that due to the brain coding the space into multiple representations, devices that make phone conversations taking place in the near, personal space make drivers slower at responding to visual stimuli, compared to devices that make the conversation occurring in a far space.

Electrochemical Visualization of Intracellular Hydrogen Peroxide at Single Cells.

PubMed

He, Ruiqin; Tang, Huifen; Jiang, Dechen; Chen, Hong-yuan

2016-02-16

In this Letter, the electrochemical visualization of hydrogen peroxide inside one cell was achieved first using a comprehensive Au-luminol-microelectrode and electrochemiluminescence. The capillary with a tip opening of 1-2 μm was filled with the mixture of chitosan and luminol, which was coated with the thin layers of polyvinyl chloride/nitrophenyloctyl ether (PVC/NPOE) and gold as the microelectrode. Upon contact with the aqueous hydrogen peroxide, hydrogen peroxide and luminol in contact with the gold layer were oxidized under the positive potential resulting in luminescence for the imaging. Due to the small diameter of the electrode, the microelectrode tip was inserted into one cell and the bright luminescence observed at the tip confirmed the visualization of intracellular hydrogen peroxide. The further coupling of oxidase on the electrode surface could open the field in the electrochemical imaging of intracellular biomolecules at single cells, which benefited the single cell electrochemical detection.

Drosophila Fatty Acid Transport Protein Regulates Rhodopsin-1 Metabolism and Is Required for Photoreceptor Neuron Survival

PubMed Central

Dourlen, Pierre; Bertin, Benjamin; Chatelain, Gilles; Robin, Marion; Napoletano, Francesco; Roux, Michel J.; Mollereau, Bertrand

2012-01-01

Tight regulation of the visual response is essential for photoreceptor function and survival. Visual response dysregulation often leads to photoreceptor cell degeneration, but the causes of such cell death are not well understood. In this study, we investigated a fatty acid transport protein (fatp) null mutation that caused adult-onset and progressive photoreceptor cell death. Consistent with fatp having a role in the retina, we showed that fatp is expressed in adult photoreceptors and accessory cells and that its re-expression in photoreceptors rescued photoreceptor viability in fatp mutants. The visual response in young fatp-mutant flies was abnormal with elevated electroretinogram amplitudes associated with high levels of Rhodopsin-1 (Rh1). Reducing Rh1 levels in rh1 mutants or depriving flies of vitamin A rescued photoreceptor cell death in fatp mutant flies. Our results indicate that fatp promotes photoreceptor survival by regulating Rh1 abundance. PMID:22844251

The impact of cataract surgery on visual functioning, vision-related disability and psychological distress: a randomized controlled trial.

PubMed

Walker, Janine G; Anstey, Kaarin J; Hennessy, Michael P; Lord, Stephen R; von Sanden, Chwee

2006-11-01

Determine whether there are changes in visual functioning, vision-related disability, health status and mood after cataract surgery. 45 adults (mean age = 73.7 years) with bilateral cataract needing surgery for the first eye were recruited from public ophthalmology clinics. The Visual Functioning-14 survey assessed visual disability. Minimal angle of resolution tested visual acuity, and the Melbourne Edge Test examined contrast sensitivity. Demographic, psychological, health and medication use variables were examined. Participants were randomized to either an intervention or control arm. Controls were assessed on two occasions at a 3-month interval before having surgery. The intervention group was assessed 1-2 weeks before surgery and then reassessed 3 months after surgery. Visual functioning improved for those who had cataract surgery with better visual acuity in the better (P = 0.010) and worse (P = 0.028) eye compared with controls. The intervention group reported fewer difficulties with overall vision-related disability (P = 0.0001), reading (P = 0.004) and instrumental activities of daily living (P = 0.010) post-surgery compared with controls. People with improved depression scores (P = 0.048) after surgery had less difficulty with reading compared with those with unchanged or worsened depression scores. Cataract surgery did not improve health status. First eye cataract surgery is effective in improving outcomes in visual functioning and disability. Improved mood after surgery was related to less vision-related disability compared with unchanged or worse depression.

Perceptual training yields rapid improvements in visually impaired youth.

PubMed

Nyquist, Jeffrey B; Lappin, Joseph S; Zhang, Ruyuan; Tadin, Duje

2016-11-30

Visual function demands coordinated responses to information over a wide field of view, involving both central and peripheral vision. Visually impaired individuals often seem to underutilize peripheral vision, even in absence of obvious peripheral deficits. Motivated by perceptual training studies with typically sighted adults, we examined the effectiveness of perceptual training in improving peripheral perception of visually impaired youth. Here, we evaluated the effectiveness of three training regimens: (1) an action video game, (2) a psychophysical task that combined attentional tracking with a spatially and temporally unpredictable motion discrimination task, and (3) a control video game. Training with both the action video game and modified attentional tracking yielded improvements in visual performance. Training effects were generally larger in the far periphery and appear to be stable 12 months after training. These results indicate that peripheral perception might be under-utilized by visually impaired youth and that this underutilization can be improved with only ~8 hours of perceptual training. Moreover, the similarity of improvements following attentional tracking and action video-game training suggest that well-documented effects of action video-game training might be due to the sustained deployment of attention to multiple dynamic targets while concurrently requiring rapid attending and perception of unpredictable events.

Evaluation of results of cell electrophoresis experiments on space shuttle STS-3 including pre-flight and post-flight laboratory experiments

NASA Technical Reports Server (NTRS)

Todd, P. W.

1985-01-01

The objectives of the red blood cell experiments were to provide a visual check on the electrophoretic process and especially electroosmotic flow in space as well as to provide test separations of non-degradable standard particles for comparison with the separations of the three viable cell types studied on the Apollo-Soyuz Test Project. Determination of the maximum concentrations of cells that can be separated in column electrophore was a significant goal. Two of the eight columns were available for red cell experiments, so two concentrations of human and rabbit RBC mixtures were used. The objectives of another experiment were to evaluate the reproducibility of microgravity electrophoretic separation of living kidney cells, to separate cells with highly viability despite two freeze-thaw cycles, and to optimize the physical conditions of cell separation. Owing to the uncertain heterogeneity of the starting material, the experimental design does not assess resolution in microgravity, but improved separability was sought in comparison to density-gradient electrophoresis or continuous-flow electrophoresis. Efforts were made to increase cell yield and cell viability and to assess reproducibility directly.

AquaLase versus NeoSoniX--a comparison study.

PubMed

Jiraskova, Nada; Rozsival, Pavel; Kadlecova, Jana; Nekolova, Jana; Pozlerova, Jana; Dubravska, Zlatica

2007-12-01

To compare the metrics and surgical outcome when using Infiniti AquaLase and NeoSoniX cataract removal modalities. This prospective clinical study involved 50 patients with bilateral cataracts and lens removal using AquaLase in the right eye and NeoSoniX in the left eye. Best corrected visual acuity (BCVA), endothelial cell density and pachymetry were evaluted pre- and postoperatively. Statistical analysis was performed using the Wilcoxon Signed- Rank Test. Preoperative mean pachymetry was 569 +/- 31 mu in the right eye (RE) and 560 +/- 37 mu in the left eye (LE), mean endothelial cell density 2744 +/- 418 cells/mm(2) (RE) and 2730 +/- 472 cells/mm(2) (LE). One week after operation pachymetry was 576 +/- 52 mu (RE) and 583 +/- 72 mu (LE) and endothelial cell density 2388 +/- 586 cells/mm(2) (RE) and 2463 +/- 615 cells/mm(2) (LE). One month after surgery pachymetry was 556 +/- 43 mu (RE) and 559 +/- 44 mu (LE) and endothelial cell density 2368 +/- 52 cells/mm(2) (RE) and 2495 +/- 548 cells/mm(2) (LE). BCVA improved in all eyes and was 0.8 or better on the first postoperative day. Both the NeosoniX and AquaLase minimize intraoperative damage to ocular structures.

NaviCell Web Service for network-based data visualization.

PubMed

Bonnet, Eric; Viara, Eric; Kuperstein, Inna; Calzone, Laurence; Cohen, David P A; Barillot, Emmanuel; Zinovyev, Andrei

2015-07-01

Data visualization is an essential element of biological research, required for obtaining insights and formulating new hypotheses on mechanisms of health and disease. NaviCell Web Service is a tool for network-based visualization of 'omics' data which implements several data visual representation methods and utilities for combining them together. NaviCell Web Service uses Google Maps and semantic zooming to browse large biological network maps, represented in various formats, together with different types of the molecular data mapped on top of them. For achieving this, the tool provides standard heatmaps, barplots and glyphs as well as the novel map staining technique for grasping large-scale trends in numerical values (such as whole transcriptome) projected onto a pathway map. The web service provides a server mode, which allows automating visualization tasks and retrieving data from maps via RESTful (standard HTTP) calls. Bindings to different programming languages are provided (Python and R). We illustrate the purpose of the tool with several case studies using pathway maps created by different research groups, in which data visualization provides new insights into molecular mechanisms involved in systemic diseases such as cancer and neurodegenerative diseases. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

NaviCell Web Service for network-based data visualization

PubMed Central

Bonnet, Eric; Viara, Eric; Kuperstein, Inna; Calzone, Laurence; Cohen, David P. A.; Barillot, Emmanuel; Zinovyev, Andrei

2015-01-01

Data visualization is an essential element of biological research, required for obtaining insights and formulating new hypotheses on mechanisms of health and disease. NaviCell Web Service is a tool for network-based visualization of ‘omics’ data which implements several data visual representation methods and utilities for combining them together. NaviCell Web Service uses Google Maps and semantic zooming to browse large biological network maps, represented in various formats, together with different types of the molecular data mapped on top of them. For achieving this, the tool provides standard heatmaps, barplots and glyphs as well as the novel map staining technique for grasping large-scale trends in numerical values (such as whole transcriptome) projected onto a pathway map. The web service provides a server mode, which allows automating visualization tasks and retrieving data from maps via RESTful (standard HTTP) calls. Bindings to different programming languages are provided (Python and R). We illustrate the purpose of the tool with several case studies using pathway maps created by different research groups, in which data visualization provides new insights into molecular mechanisms involved in systemic diseases such as cancer and neurodegenerative diseases. PMID:25958393

The application of autologous serum eye drops in severe dry eye patients; subjective and objective parameters before and after treatment.

PubMed

Jirsova, Katerina; Brejchova, Kristyna; Krabcova, Ivana; Filipec, Martin; Al Fakih, Aref; Palos, Michalis; Vesela, Viera

2014-01-01

To assess the impact of autologous serum (AS) eye drops on the ocular surface of patients with bilateral severe dry eye and to draw a comparison between the clinical and laboratory examinations and the degree of subjective symptoms before and after serum treatment. A three-month prospective study was conducted on 17 patients with severe dry eye. AS eye drops were applied a maximum of 12 times a day together with regular therapy. Dry eye status was evaluated by clinical examination (visual acuity, Schirmer test, tear film breakup time, vital staining, tear film debris and meniscus), conjunctival impression cytology (epithelial and goblet cell density, snake-like chromatin, HLA-DR-positive and apoptotic cells) and subjectively by the patients. The application of AS eye drops led to a significant improvement in the Schirmer test (p < 0.01) and tear film debris (p < 0.05). The densities of goblet (p < 0.0001) and epithelial cells (p < 0.05) were significantly increased, indicating a decrease of squamous metaplasia after AS treatment. A significant decrease (p < 0.05) was found in the number of apoptotic, HLA-DR-positive and snake-like chromatin cells on the ocular surface. A significant improvement was found in all evaluated subjective symptoms. Altogether, the clinical results were improved in 77%, the laboratory results in 75% and the subjective feelings in 63% of the eyes. We found that three-month AS treatment led especially to the improvement of ocular surface dryness and damage of the epithelium. The improvement of dry eye after AS treatment correlated well with the clinical, laboratory and subjective findings. From the patients' subjective point of view, the positive effect of AS decreased with time, but still persisted up to three months after the end of therapy.

Fibered Confocal Fluorescence Microscopy for the Noninvasive Imaging of Langerhans Cells in Macaques.

PubMed

Todorova, Biliana; Salabert, Nina; Tricot, Sabine; Boisgard, Raphaël; Rathaux, Mélanie; Le Grand, Roger; Chapon, Catherine

2017-01-01

We developed a new approach to visualize skin Langerhans cells by in vivo fluorescence imaging in nonhuman primates. Macaques were intradermally injected with a monoclonal, fluorescently labeled antibody against HLA-DR molecule and were imaged for up to 5 days by fibered confocal microscopy (FCFM). The network of skin Langerhans cells was visualized by in vivo fibered confocal fluorescence microscopy. Quantification of Langerhans cells revealed no changes to cell density with time. Ex vivo experiments confirmed that injected fluorescent HLA-DR antibody specifically targeted Langerhans cells in the epidermis. This study demonstrates the feasibility of single-cell, in vivo imaging as a noninvasive technique to track Langerhans cells in nontransgenic animals.

Direct Visualization of Wide Fusion-Fission Pores and Their Highly Varied Dynamics.

PubMed

Eyring, Katherine W; Tsien, Richard W

2018-05-03

In this issue of Cell, Shin et al. report the first live-cell imaging of a fusion pore. Directly visualized pores in neuroendocrine cells can be much larger than expected yet not require vesicular full-collapse. These fusion-fission pores have diverse fates arising from opposing dynamin-driven pore constriction and F-actin-mediated pore expansion. Copyright © 2018. Published by Elsevier Inc.

Catch the live show: Visualizing damaged DNA in vivo.

PubMed

Oshidari, Roxanne; Mekhail, Karim

2018-06-01

The health of an organism is intimately linked to its ability to repair damaged DNA. Importantly, DNA repair processes are highly dynamic. This highlights the necessity of characterizing DNA repair in live cells. Advanced genome editing and imaging approaches allow us to visualize damaged DNA and its associated factors in real time. Here, we summarize both established and recent methods that are used to induce DNA damage and visualize damaged DNA and its repair in live cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Binocular disparity tuning and visual-vestibular congruency of multisensory neurons in macaque parietal cortex

PubMed Central

Yang, Yun; Liu, Sheng; Chowdhury, Syed A.; DeAngelis, Gregory C.; Angelaki, Dora E.

2012-01-01

Many neurons in the dorsal medial superior temporal (MSTd) and ventral intraparietal (VIP) areas of the macaque brain are multisensory, responding to both optic flow and vestibular cues to self-motion. The heading tuning of visual and vestibular responses can be either congruent or opposite, but only congruent cells have been implicated in cue integration for heading perception. Because of the geometric properties of motion parallax, however, both congruent and opposite cells could be involved in coding self-motion when observers fixate a world-fixed target during translation, if congruent cells prefer near disparities and opposite cells prefer far disparities. We characterized the binocular disparity selectivity and heading tuning of MSTd and VIP cells using random-dot stimuli. Most (70%) MSTd neurons were disparity-selective with monotonic tuning, and there was no consistent relationship between depth preference and congruency of visual and vestibular heading tuning. One-third of disparity-selective MSTd cells reversed their depth preference for opposite directions of motion (direction-dependent disparity tuning, DDD), but most of these cells were unisensory with no tuning for vestibular stimuli. Inconsistent with previous reports, the direction preferences of most DDD neurons do not reverse with disparity. By comparison to MSTd, VIP contains fewer disparity-selective neurons (41%) and very few DDD cells. On average, VIP neurons also preferred higher speeds and nearer disparities than MSTd cells. Our findings are inconsistent with the hypothesis that visual/vestibular congruency is linked to depth preference, and also suggest that DDD cells are not involved in multisensory integration for heading perception. PMID:22159105

Therapeutic Cell-Cycle-Decoy Efficacy of a Telomerase-Dependent Adenovirus in an Orthotopic Model of Chemotherapy-Resistant Human Stomach Carcinomatosis Peritonitis Visualized With FUCCI Imaging.

PubMed

Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

2017-11-01

We have established an orthotopic nude-mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease in human patients. Human MKN45 poorly-differentiated human gastric cancer cells developed carcinomatosis peritonitis upon orthotopic transplantation in nude mice. The MKN45 cells expressed the fluorescent ubiquitination-based cell cycle indicator (FUCCI) that color codes the phases of the cell cycle. The intra-peritoneal tumors and ascites contained mostly quiescent G 1 /G o cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors formed in the peritoneal cavity after CDDP treatment in an early-stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel-treated mice had reduced ascites, but also had large tumor masses in the peritonium after treatment with cancer cells mostly in G 0 /G 1 , visualized by FUCCI red. In contrast, OBP-301 telomerase-dependent adenovirus-treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G 2 phases in the early-stage carcinomatosis peritonitis model, visualized by FUCCI green. Furthermore, OBP-301 significantly reduced the size of tumors (P < 0.01) and ascites even in a late-stage carcinomatosis peritonitis model. These results suggest that quiescent peritoneally-disseminated gastric cancer cells are resistant to conventional chemotherapy, but OBP-301 significantly reduced the weight of the tumors and increased survival, suggesting clinical potential. J. Cell. Biochem. 118: 3635-3642, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Parasol cell mosaics are unlikely to drive the formation of structured orientation maps in primary visual cortex.

PubMed

Hore, Victoria R A; Troy, John B; Eglen, Stephen J

2012-11-01

The receptive fields of on- and off-center parasol cell mosaics independently tile the retina to ensure efficient sampling of visual space. A recent theoretical model represented the on- and off-center mosaics by noisy hexagonal lattices of slightly different density. When the two lattices are overlaid, long-range Moiré interference patterns are generated. These Moiré interference patterns have been suggested to drive the formation of highly structured orientation maps in visual cortex. Here, we show that noisy hexagonal lattices do not capture the spatial statistics of parasol cell mosaics. An alternative model based upon local exclusion zones, termed as the pairwise interaction point process (PIPP) model, generates patterns that are statistically indistinguishable from parasol cell mosaics. A key difference between the PIPP model and the hexagonal lattice model is that the PIPP model does not generate Moiré interference patterns, and hence stimulated orientation maps do not show any hexagonal structure. Finally, we estimate the spatial extent of spatial correlations in parasol cell mosaics to be only 200-350 μm, far less than that required to generate Moiré interference. We conclude that parasol cell mosaics are too disordered to drive the formation of highly structured orientation maps in visual cortex.

How vision and movement combine in the hippocampal place code.

PubMed

Chen, Guifen; King, John A; Burgess, Neil; O'Keefe, John

2013-01-02

How do external environmental and internal movement-related information combine to tell us where we are? We examined the neural representation of environmental location provided by hippocampal place cells while mice navigated a virtual reality environment in which both types of information could be manipulated. Extracellular recordings were made from region CA1 of head-fixed mice navigating a virtual linear track and running in a similar real environment. Despite the absence of vestibular motion signals, normal place cell firing and theta rhythmicity were found. Visual information alone was sufficient for localized firing in 25% of place cells and to maintain a local field potential theta rhythm (but with significantly reduced power). Additional movement-related information was required for normally localized firing by the remaining 75% of place cells. Trials in which movement and visual information were put into conflict showed that they combined nonlinearly to control firing location, and that the relative influence of movement versus visual information varied widely across place cells. However, within this heterogeneity, the behavior of fully half of the place cells conformed to a model of path integration in which the presence of visual cues at the start of each run together with subsequent movement-related updating of position was sufficient to maintain normal fields.

Sampling versus systematic full lymphatic dissection in surgical treatment of non-small cell lung cancer.

PubMed

Koulaxouzidis, Georgios; Karagkiouzis, Grigorios; Konstantinou, Marios; Gkiozos, Ioannis; Syrigos, Konstantinos

2013-04-22

The extent of mediastinal lymph node assessment during surgery for non-small cell cancer remains controversial. Different techniques are used, ranging from simple visual inspection of the unopened mediastinum to an extended bilateral lymph node dissection. Furthermore, different terms are used to define these techniques. Sampling is the removal of one or more lymph nodes under the guidance of pre-operative findings. Systematic (full) nodal dissection is the removal of all mediastinal tissue containing the lymph nodes systematically within anatomical landmarks. A Medline search was conducted to identify articles in the English language that addressed the role of mediastinal lymph node resection in the treatment of non-small cell lung cancer. Opinions as to the reasons for favoring full lymphatic dissection include complete resection, improved nodal staging and better local control due to resection of undetected micrometastasis. Arguments against routine full lymphatic dissection are increased morbidity, increase in operative time, and lack of evidence of improved survival. For complete resection of non-small cell lung cancer, many authors recommend a systematic nodal dissection as the standard approach during surgery, and suggest that this provides both adequate nodal staging and guarantees complete resection. Whether extending the lymph node dissection influences survival or recurrence rate is still not known. There are valid arguments in favor in terms not only of an improved local control but also of an improved long-term survival. However, the impact of lymph node dissection on long-term survival should be further assessed by large-scale multicenter randomized trials.

Evaluation of an iPhone Otoscope in a Neurotrauma Clinic and as an Adjunct to Neurosurgical Education.

PubMed

Sahyouni, Ronald; Moshtaghi, Omid; Rajaii, Ramin; Tran, Diem Kieu; Bustillo, David; Huang, Melissa; Chen, Jefferson W

CellScope ® , an iPhone-enabled otoscope, was introduced into the neurotrauma clinic at an American College of Surgeons certified Level I trauma center. CellScope is an innovative tool that digitally improves optical clarity of the tympanic membrane, providing the acquisition of HIPPA compliant images. We compared the CellScope to the traditional otoscope in teaching medical students, neurosurgery physician assistants, and neurosurgery residents. In addition, the utility of this device in a neurotrauma clinic was specifically examined because of the high frequency of otologic symptoms after head trauma. CellScope examination of the tympanic membranes was introduced as a standard/routine part of the exam of neurotrauma patients. We retrospectively reviewed the clinic charts of the NeuroTrauma patients during a three-month time period to determine if their otologic symptoms correlated with any CellScope visualized abnormalities. Medical students, P.A.s, residents, and attendings were surveyed before and after using CellScope to assess their comfort and skill in completing an otological exam, as well as their opinion on the utility of CellScope in their medical training. 18 medical professionals were surveyed before and after the use of CellScope. Surveys were graded on a 1-5 scale and indicated a greater preference for the CellScope (4.7/5.0) versus the otoscope (3.16/5.0). Similarly, there was a preference for the CellScope for medical education (4.7/5.0 versus 2.78/5.0). Finally, surveys showed a greater preference for CellScope in identifying abnormal pathology. The overall score showed a 49% increased preference for CellScope over the traditional otoscope. Six previously undiagnosed abnormalities of the tympanic membrane were identified in a total of 27 neurotrauma patients using CellScope. The visualization of the tympanic membrane is an important part of the physical examination of the neurotrauma patient. Smartphone-enabled medical instruments like CellScope may facilitate and remove barriers to routine implementation of this part of the physical examination.

Evaluation of an iPhone Otoscope in a Neurotrauma Clinic and as an Adjunct to Neurosurgical Education

PubMed Central

Sahyouni, Ronald; Moshtaghi, Omid; Rajaii, Ramin; Tran, Diem Kieu; Bustillo, David; Huang, Melissa; Chen, Jefferson W

2016-01-01

Introduction CellScope®, an iPhone-enabled otoscope, was introduced into the neurotrauma clinic at an American College of Surgeons certified Level I trauma center. CellScope is an innovative tool that digitally improves optical clarity of the tympanic membrane, providing the acquisition of HIPPA compliant images. We compared the CellScope to the traditional otoscope in teaching medical students, neurosurgery physician assistants, and neurosurgery residents. In addition, the utility of this device in a neurotrauma clinic was specifically examined because of the high frequency of otologic symptoms after head trauma. Method CellScope examination of the tympanic membranes was introduced as a standard/routine part of the exam of neurotrauma patients. We retrospectively reviewed the clinic charts of the NeuroTrauma patients during a three-month time period to determine if their otologic symptoms correlated with any CellScope visualized abnormalities. Medical students, P.A.s, residents, and attendings were surveyed before and after using CellScope to assess their comfort and skill in completing an otological exam, as well as their opinion on the utility of CellScope in their medical training. Results 18 medical professionals were surveyed before and after the use of CellScope. Surveys were graded on a 1-5 scale and indicated a greater preference for the CellScope (4.7/5.0) versus the otoscope (3.16/5.0). Similarly, there was a preference for the CellScope for medical education (4.7/5.0 versus 2.78/5.0). Finally, surveys showed a greater preference for CellScope in identifying abnormal pathology. The overall score showed a 49% increased preference for CellScope over the traditional otoscope. Six previously undiagnosed abnormalities of the tympanic membrane were identified in a total of 27 neurotrauma patients using CellScope. Conclusion The visualization of the tympanic membrane is an important part of the physical examination of the neurotrauma patient. Smartphone-enabled medical instruments like CellScope may facilitate and remove barriers to routine implementation of this part of the physical examination. PMID:27135057

Distinct learning-induced changes in stimulus selectivity and interactions of GABAergic interneuron classes in visual cortex.

PubMed

Khan, Adil G; Poort, Jasper; Chadwick, Angus; Blot, Antonin; Sahani, Maneesh; Mrsic-Flogel, Thomas D; Hofer, Sonja B

2018-06-01

How learning enhances neural representations for behaviorally relevant stimuli via activity changes of cortical cell types remains unclear. We simultaneously imaged responses of pyramidal cells (PYR) along with parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP) inhibitory interneurons in primary visual cortex while mice learned to discriminate visual patterns. Learning increased selectivity for task-relevant stimuli of PYR, PV and SOM subsets but not VIP cells. Strikingly, PV neurons became as selective as PYR cells, and their functional interactions reorganized, leading to the emergence of stimulus-selective PYR-PV ensembles. Conversely, SOM activity became strongly decorrelated from the network, and PYR-SOM coupling before learning predicted selectivity increases in individual PYR cells. Thus, learning differentially shapes the activity and interactions of multiple cell classes: while SOM inhibition may gate selectivity changes, PV interneurons become recruited into stimulus-specific ensembles and provide more selective inhibition as the network becomes better at discriminating behaviorally relevant stimuli.

Distinct responses of Purkinje neurons and roles of simple spikes during associative motor learning in larval zebrafish

PubMed Central

Harmon, Thomas C; Magaram, Uri; McLean, David L; Raman, Indira M

2017-01-01

To study cerebellar activity during learning, we made whole-cell recordings from larval zebrafish Purkinje cells while monitoring fictive swimming during associative conditioning. Fish learned to swim in response to visual stimulation preceding tactile stimulation of the tail. Learning was abolished by cerebellar ablation. All Purkinje cells showed task-related activity. Based on how many complex spikes emerged during learned swimming, they were classified as multiple, single, or zero complex spike (MCS, SCS, ZCS) cells. With learning, MCS and ZCS cells developed increased climbing fiber (MCS) or parallel fiber (ZCS) input during visual stimulation; SCS cells fired complex spikes associated with learned swimming episodes. The categories correlated with location. Optogenetically suppressing simple spikes only during visual stimulation demonstrated that simple spikes are required for acquisition and early stages of expression of learned responses, but not their maintenance, consistent with a transient, instructive role for simple spikes during cerebellar learning in larval zebrafish. DOI: http://dx.doi.org/10.7554/eLife.22537.001 PMID:28541889

Nanohybrids with Magnetic and Persistent Luminescence Properties for Cell Labeling, Tracking, In Vivo Real-Time Imaging, and Magnetic Vectorization.

PubMed

Teston, Eliott; Maldiney, Thomas; Marangon, Iris; Volatron, Jeanne; Lalatonne, Yoann; Motte, Laurence; Boisson-Vidal, Catherine; Autret, Gwennhael; Clément, Olivier; Scherman, Daniel; Gazeau, Florence; Richard, Cyrille

2018-04-01

Once injected into a living organism, cells diffuse or migrate around the initial injection point and become impossible to be visualized and tracked in vivo. The present work concerns the development of a new technique for therapeutic cell labeling and subsequent in vivo visualization and magnetic retention. It is hypothesized and subsequently demonstrated that nanohybrids made of persistent luminescence nanoparticles and ultrasmall superparamagnetic iron oxide nanoparticles incorporated into a silica matrix can be used as an effective nanoplatform to label therapeutic cells in a nontoxic way in order to dynamically track them in real-time in vitro and in living mice. As a proof-of-concept, it is shown that once injected, these labeled cells can be visualized and attracted in vivo using a magnet. This first step suggests that these nanohybrids represent efficient multifunctional nanoprobes for further imaging guided cell therapies development. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Model of Generating Visual Place Cells Based on Environment Perception and Similar Measure.

PubMed

Zhou, Yang; Wu, Dewei

2016-01-01

It is an important content to generate visual place cells (VPCs) in the field of bioinspired navigation. By analyzing the firing characteristic of biological place cells and the existing methods for generating VPCs, a model of generating visual place cells based on environment perception and similar measure is abstracted in this paper. VPCs' generation process is divided into three phases, including environment perception, similar measure, and recruiting of a new place cell. According to this process, a specific method for generating VPCs is presented. External reference landmarks are obtained based on local invariant characteristics of image and a similar measure function is designed based on Euclidean distance and Gaussian function. Simulation validates the proposed method is available. The firing characteristic of the generated VPCs is similar to that of biological place cells, and VPCs' firing fields can be adjusted flexibly by changing the adjustment factor of firing field (AFFF) and firing rate's threshold (FRT).

A Model of Generating Visual Place Cells Based on Environment Perception and Similar Measure

PubMed Central

2016-01-01

It is an important content to generate visual place cells (VPCs) in the field of bioinspired navigation. By analyzing the firing characteristic of biological place cells and the existing methods for generating VPCs, a model of generating visual place cells based on environment perception and similar measure is abstracted in this paper. VPCs' generation process is divided into three phases, including environment perception, similar measure, and recruiting of a new place cell. According to this process, a specific method for generating VPCs is presented. External reference landmarks are obtained based on local invariant characteristics of image and a similar measure function is designed based on Euclidean distance and Gaussian function. Simulation validates the proposed method is available. The firing characteristic of the generated VPCs is similar to that of biological place cells, and VPCs' firing fields can be adjusted flexibly by changing the adjustment factor of firing field (AFFF) and firing rate's threshold (FRT). PMID:27597859

Corticothalamic feedback enhances stimulus response precision in the visual system

PubMed Central

Andolina, Ian M.; Jones, Helen E.; Wang, Wei; Sillito, Adam M.

2007-01-01

There is a tightly coupled bidirectional interaction between visual cortex and visual thalamus [lateral geniculate nucleus (LGN)]. Using drifting sinusoidal grating stimuli, we compared the response of cells in the LGN with and without feedback from the visual cortex. Raster plots revealed a striking difference in the response pattern of cells with and without feedback. This difference was reflected in the results from computing vector sum plots and the ratio of zero harmonic to the fundamental harmonic of the fast Fourier transform (FFT) for these responses. The variability of responses assessed by using the Fano factor was also different for the two groups, with the cells without feedback showing higher variability. We examined the covariance of these measures between pairs of simultaneously recorded cells with and without feedback, and they were much more strongly positively correlated with feedback. We constructed orientation tuning curves from the central 5 ms in the raw cross-correlograms of the outputs of pairs of LGN cells, and these curves revealed much sharper tuning with feedback. We discuss the significance of these data for cortical function and suggest that the precision in stimulus-linked firing in the LGN appears as an emergent factor from the corticothalamic interaction. PMID:17237220

Distinctive receptive field and physiological properties of a wide-field amacrine cell in the macaque monkey retina

PubMed Central

Puller, Christian; Rieke, Fred; Neitz, Jay; Neitz, Maureen

2015-01-01

At early stages of visual processing, receptive fields are typically described as subtending local regions of space and thus performing computations on a narrow spatial scale. Nevertheless, stimulation well outside of the classical receptive field can exert clear and significant effects on visual processing. Given the distances over which they occur, the retinal mechanisms responsible for these long-range effects would certainly require signal propagation via active membrane properties. Here the physiology of a wide-field amacrine cell—the wiry cell—in macaque monkey retina is explored, revealing receptive fields that represent a striking departure from the classic structure. A single wiry cell integrates signals over wide regions of retina, 5–10 times larger than the classic receptive fields of most retinal ganglion cells. Wiry cells integrate signals over space much more effectively than predicted from passive signal propagation, and spatial integration is strongly attenuated during blockade of NMDA spikes but integration is insensitive to blockade of NaV channels with TTX. Thus these cells appear well suited for contributing to the long-range interactions of visual signals that characterize many aspects of visual perception. PMID:26133804

Efficacy and Safety of Human Retinal Progenitor Cells

PubMed Central

Semo, Ma'ayan; Haamedi, Nasrin; Stevanato, Lara; Carter, David; Brooke, Gary; Young, Michael; Coffey, Peter; Sinden, John; Patel, Sara; Vugler, Anthony

2016-01-01

Purpose We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. Methods Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting. Safety of hRPC was assessed by subretinal transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at 3 to 6 and 9 months after grafting, respectively. Results The optimal dose of hRPC for preserving visual function/retinal structure in dystrophic rats was 50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in dystrophic and WT rat retina up to 6 months after grafting and expressed nestin, vimentin, GFAP, and βIII tubulin. Vision and retinal structure remained normal in WT rats injected with hRPC and there was no evidence of tumors. A comparison between dexamethasone-treated and untreated dystrophic rats at 3 months after grafting revealed an unexpected reduction in the baseline visual acuity of dexamethasone-treated animals. Conclusions Human retinal progenitor cells appear safe and efficacious in the preclinical models used here. Translational Relevance Human retinal progenitor cells could be deployed during early stages of retinal degeneration or in regions of intact retina, without adverse effects on visual function. The ability of dexamethasone to reduce baseline visual acuity in RCS dystrophic rats has important implications for the interpretation of preclinical and clinical cell transplant studies. PMID:27486556

The Effects of Compensatory Scanning Training on Mobility in Patients with Homonymous Visual Field Defects: Further Support, Predictive Variables and Follow-Up

PubMed Central

Melis-Dankers, Bart J. M.; Brouwer, Wiebo H.; Tucha, Oliver; Heutink, Joost

2016-01-01

Introduction People with homonymous visual field defects (HVFD) often report difficulty detecting obstacles in the periphery on their blind side in time when moving around. Recently, a randomized controlled trial showed that the InSight-Hemianopia Compensatory Scanning Training (IH-CST) specifically improved detection of peripheral stimuli and avoiding obstacles when moving around, especially in dual task situations. Method The within-group training effects of the previously reported IH-CST are examined in an extended patient group. Performance of patients with HVFD on a pre-assessment, post-assessment and follow-up assessment and performance of a healthy control group are compared. Furthermore, it is examined whether training effects can be predicted by demographic characteristics, variables related to the visual disorder, and neuropsychological test results. Results Performance on both subjective and objective measures of mobility-related scanning was improved after training, while no evidence was found for improvement in visual functions (including visual fields), reading, visual search and dot counting. Self-reported improvement did not correlate with improvement in objective mobility performance. According to the participants, the positive effects were still present six to ten months after training. No demographic characteristics, variables related to the visual disorder, and neuropsychological test results were found to predict the size of training effect, although some inconclusive evidence was found for more improvement in patients with left-sided HVFD than in patients with right-sided HFVD. Conclusion Further support was found for a positive effect of IH-CST on detection of visual stimuli during mobility-related activities specifically. Based on the reports given by patients, these effects appear to be long-term effects. However, no conclusions can be drawn on the objective long-term training effects. PMID:27935973

Big data in medical informatics: improving education through visual analytics.

PubMed

Vaitsis, Christos; Nilsson, Gunnar; Zary, Nabil

2014-01-01

A continuous effort to improve healthcare education today is currently driven from the need to create competent health professionals able to meet healthcare demands. Limited research reporting how educational data manipulation can help in healthcare education improvement. The emerging research field of visual analytics has the advantage to combine big data analysis and manipulation techniques, information and knowledge representation, and human cognitive strength to perceive and recognise visual patterns. The aim of this study was therefore to explore novel ways of representing curriculum and educational data using visual analytics. Three approaches of visualization and representation of educational data were presented. Five competencies at undergraduate medical program level addressed in courses were identified to inaccurately correspond to higher education board competencies. Different visual representations seem to have a potential in impacting on the ability to perceive entities and connections in the curriculum data.

Evolution and the origin of the visual retinoid cycle in vertebrates.

PubMed

Kusakabe, Takehiro G; Takimoto, Noriko; Jin, Minghao; Tsuda, Motoyuki

2009-10-12

Absorption of a photon by visual pigments induces isomerization of 11-cis-retinaldehyde (RAL) chromophore to all-trans-RAL. Since the opsins lacking 11-cis-RAL lose light sensitivity, sustained vision requires continuous regeneration of 11-cis-RAL via the process called 'visual cycle'. Protostomes and vertebrates use essentially different machinery of visual pigment regeneration, and the origin and early evolution of the vertebrate visual cycle is an unsolved mystery. Here we compare visual retinoid cycles between different photoreceptors of vertebrates, including rods, cones and non-visual photoreceptors, as well as between vertebrates and invertebrates. The visual cycle systems in ascidians, the closest living relatives of vertebrates, show an intermediate state between vertebrates and non-chordate invertebrates. The ascidian larva may use retinochrome-like opsin as the major isomerase. The entire process of the visual cycle can occur inside the photoreceptor cells with distinct subcellular compartmentalization, although the visual cycle components are also present in surrounding non-photoreceptor cells. The adult ascidian probably uses RPE65 isomerase, and trans-to-cis isomerization may occur in distinct cellular compartments, which is similar to the vertebrate situation. The complete transition to the sophisticated retinoid cycle of vertebrates may have required acquisition of new genes, such as interphotoreceptor retinoid-binding protein, and functional evolution of the visual cycle genes.

Learning and disrupting invariance in visual recognition with a temporal association rule

PubMed Central

Isik, Leyla; Leibo, Joel Z.; Poggio, Tomaso

2012-01-01

Learning by temporal association rules such as Foldiak's trace rule is an attractive hypothesis that explains the development of invariance in visual recognition. Consistent with these rules, several recent experiments have shown that invariance can be broken at both the psychophysical and single cell levels. We show (1) that temporal association learning provides appropriate invariance in models of object recognition inspired by the visual cortex, (2) that we can replicate the “invariance disruption” experiments using these models with a temporal association learning rule to develop and maintain invariance, and (3) that despite dramatic single cell effects, a population of cells is very robust to these disruptions. We argue that these models account for the stability of perceptual invariance despite the underlying plasticity of the system, the variability of the visual world and expected noise in the biological mechanisms. PMID:22754523

Response-dependent dynamics of cell-specific inhibition in cortical networks in vivo

PubMed Central

El-Boustani, Sami; Sur, Mriganka

2014-01-01

In the visual cortex, inhibitory neurons alter the computations performed by target cells via combination of two fundamental operations, division and subtraction. The origins of these operations have been variously ascribed to differences in neuron classes, synapse location or receptor conductances. Here, by utilizing specific visual stimuli and single optogenetic probe pulses, we show that the function of parvalbumin-expressing and somatostatin-expressing neurons in mice in vivo is governed by the overlap of response timing between these neurons and their targets. In particular, somatostatin-expressing neurons respond at longer latencies to small visual stimuli compared with their target neurons and provide subtractive inhibition. With large visual stimuli, however, they respond at short latencies coincident with their target cells and switch to provide divisive inhibition. These results indicate that inhibition mediated by these neurons is a dynamic property of cortical circuits rather than an immutable property of neuronal classes. PMID:25504329

LRRTM1 underlies synaptic convergence in visual thalamus

PubMed Central

Monavarfeshani, Aboozar; Stanton, Gail; Van Name, Jonathan; Su, Kaiwen; Mills, William A; Swilling, Kenya; Kerr, Alicia; Huebschman, Natalie A; Su, Jianmin

2018-01-01

It has long been thought that the mammalian visual system is organized into parallel pathways, with incoming visual signals being parsed in the retina based on feature (e.g. color, contrast and motion) and then transmitted to the brain in unmixed, feature-specific channels. To faithfully convey feature-specific information from retina to cortex, thalamic relay cells must receive inputs from only a small number of functionally similar retinal ganglion cells. However, recent studies challenged this by revealing substantial levels of retinal convergence onto relay cells. Here, we sought to identify mechanisms responsible for the assembly of such convergence. Using an unbiased transcriptomics approach and targeted mutant mice, we discovered a critical role for the synaptic adhesion molecule Leucine Rich Repeat Transmembrane Neuronal 1 (LRRTM1) in the emergence of retinothalamic convergence. Importantly, LRRTM1 mutant mice display impairment in visual behaviors, suggesting a functional role of retinothalamic convergence in vision. PMID:29424692

Memory as Perception of the Past: Compressed Time inMind and Brain.

PubMed

Howard, Marc W

2018-02-01

In the visual system retinal space is compressed such that acuity decreases further from the fovea. Different forms of memory may rely on a compressed representation of time, manifested as decreased accuracy for events that happened further in the past. Neurophysiologically, "time cells" show receptive fields in time. Analogous to the compression of visual space, time cells show less acuity for events further in the past. Behavioral evidence suggests memory can be accessed by scanning a compressed temporal representation, analogous to visual search. This suggests a common computational language for visual attention and memory retrieval. In this view, time functions like a scaffolding that organizes memories in much the same way that retinal space functions like a scaffolding for visual perception. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes in corneal topography and biomechanical properties after collagen cross linking for keratoconus: 1-year results.

PubMed

Sedaghat, Mohammadreza; Bagheri, Mansooreh; Ghavami, Shahri; Bamdad, Shahram

2015-01-01

To evaluate changes in corneal topography and biomechanical properties after collagen cross-linking (CXL) for progressive keratoconus. Collagen cross-linking was performed on 97 eyes. We assessed uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA). Corneal topography indices were evaluated using placido disc topography, scanning slit anterior topography (Orbscan II), and rotating Scheimpflug topography (Pentacam). Specular microscopy and corneal biomechanics were evaluated. A 1-year-follow-up results revealed that UCVA improved from 0.31 to 0.45 and BCVA changed from 0.78 to 0.84 (P < 0.001). The mean of average keratometry value decreased from 49.62 to 47.95 D (P < 0.001). Astigmatism decreased from 4.84 to 4.24 D (P < 0.001). Apex corneal thickness decreased from 458.11 to 444.46 μm. Corneal volume decreased from 56.66 to 55.97 mm(3) (P < 0.001). Posterior best fit sphere increased from 55.50 to 46.03 mm (P = 0.025). Posterior elevation increased from 99.2 to 112.22 μm (P < 0.001). Average progressive index increased from 2.26 to 2.56 (P < 0.001). A nonsignificant decrease was observed in mean endothelial count from 2996 to 2928 cell/mm(2) (P = 0.190). Endothelial coefficient of variation (CV) increased nonsignificantly from 18.26 to 20.29 (P = 0.112). Corneal hysteresis changed from 8.18 to 8.36 (P = 0.552) and corneal resistance factor increased from 6.98 to 7.21 (P = 0.202), so these changes were not significant. Visual acuity and K values improved after CXL. In spite of the nonsignificant increase in endothelial cell count and increase in the CV, CLX seems to be a safe treatment for keratoconus. Further studies with larger sample sizes and longer follow-up periods are recommended.

Correction of low corneal astigmatism in cataract surgery.

PubMed

Leon, Pia; Pastore, Marco Rocco; Zanei, Andrea; Umari, Ingrid; Messai, Meriem; Negro, Corrado; Tognetto, Daniele

2015-01-01

To evaluate and compare aspheric toric intraocular lens (IOL) implantation and aspheric monofocal IOL implantation with limbal relaxing incisions (LRI) to manage low corneal astigmatism (1.0-2.0 D) in cataract surgery. A prospective randomized comparative clinical study was performed. There were randomly recruited 102 eyes (102 patients) with cataracts associated with corneal astigmatism and divided into two groups. The first group received toric IOL implantation and the second one monofocal IOL implantation with peripheral corneal relaxing incisions. Outcomes considered were: visual acuity, postoperative residual astigmatism, endothelial cell count, the need for spectacles, and patient satisfaction. To determine the postoperative toric axis, all patients who underwent the toric IOL implantation were further evaluated using an OPD Scan III (Nidek Co, Japan). Follow-up lasted 6mo. The mean uncorrected distance visual acuity (UCVA) and the best corrected visual acuity (BCVA) demonstrated statistically significant improvement after surgery in both groups. At the end of the follow-up the UCVA was statistically better in the patients with toric IOL implants compared to those patients who underwent implantation of monofocal IOL plus LRI. The mean residual refractive astigmatism was of 0.4 D for the toric IOL group and 1.1 D for the LRI group (P<0.01). No difference was observed in the postoperative endothelial cell count between the two groups. The two surgical procedures demonstrated a significant decrease in refractive astigmatism. Toric IOL implantation was more effective and predictable compared to the limbal relaxing incision.

Correction of low corneal astigmatism in cataract surgery

PubMed Central

Leon, Pia; Pastore, Marco Rocco; Zanei, Andrea; Umari, Ingrid; Messai, Meriem; Negro, Corrado; Tognetto, Daniele

2015-01-01

AIM To evaluate and compare aspheric toric intraocular lens (IOL) implantation and aspheric monofocal IOL implantation with limbal relaxing incisions (LRI) to manage low corneal astigmatism (1.0-2.0 D) in cataract surgery. METHODS A prospective randomized comparative clinical study was performed. There were randomly recruited 102 eyes (102 patients) with cataracts associated with corneal astigmatism and divided into two groups. The first group received toric IOL implantation and the second one monofocal IOL implantation with peripheral corneal relaxing incisions. Outcomes considered were: visual acuity, postoperative residual astigmatism, endothelial cell count, the need for spectacles, and patient satisfaction. To determine the postoperative toric axis, all patients who underwent the toric IOL implantation were further evaluated using an OPD Scan III (Nidek Co, Japan). Follow-up lasted 6mo. RESULTS The mean uncorrected distance visual acuity (UCVA) and the best corrected visual acuity (BCVA) demonstrated statistically significant improvement after surgery in both groups. At the end of the follow-up the UCVA was statistically better in the patients with toric IOL implants compared to those patients who underwent implantation of monofocal IOL plus LRI. The mean residual refractive astigmatism was of 0.4 D for the toric IOL group and 1.1 D for the LRI group (P<0.01). No difference was observed in the postoperative endothelial cell count between the two groups. CONCLUSION The two surgical procedures demonstrated a significant decrease in refractive astigmatism. Toric IOL implantation was more effective and predictable compared to the limbal relaxing incision. PMID:26309869

Ultra-high contrast retinal display system for single photoreceptor psychophysics

PubMed Central

Domdei, Niklas; Domdei, Lennart; Reiniger, Jenny L.; Linden, Michael; Holz, Frank G.; Roorda, Austin; Harmening, Wolf M.

2017-01-01

Due to the enormous dynamic range of human photoreceptors in response to light, studying their visual function in the intact retina challenges the stimulation hardware, specifically with regard to the displayable luminance contrast. The adaptive optics scanning laser ophthalmoscope (AOSLO) is an optical platform that focuses light to extremely small retinal extents, approaching the size of single photoreceptor cells. However, the current light modulation techniques produce spurious visible backgrounds which fundamentally limit experimental options. To remove unwanted background light and to improve contrast for high dynamic range visual stimulation in an AOSLO, we cascaded two commercial fiber-coupled acousto-optic modulators (AOMs) and measured their combined optical contrast. By compensating for zero-point differences in the individual AOMs, we demonstrate a multiplicative extinction ratio in the cascade that was in accordance with the extinction ratios of both single AOMs. When latency differences in the AOM response functions were individually corrected, single switch events as short as 50 ns with radiant power contrasts up to 1:1010 were achieved. This is the highest visual contrast reported for any display system so far. We show psychophysically that this contrast ratio is sufficient to stimulate single foveal photoreceptor cells with small and bright enough visible targets that do not contain a detectable background. Background-free stimulation will enable photoreceptor testing with custom adaptation lights. Furthermore, a larger dynamic range in displayable light levels can drive photoreceptor responses in cones as well as in rods. PMID:29359094

Closed-Loop Efficient Searching of Optimal Electrical Stimulation Parameters for Preferential Excitation of Retinal Ganglion Cells

PubMed Central

Guo, Tianruo; Yang, Chih Yu; Tsai, David; Muralidharan, Madhuvanthi; Suaning, Gregg J.; Morley, John W.; Dokos, Socrates; Lovell, Nigel H.

2018-01-01

The ability for visual prostheses to preferentially activate functionally-distinct retinal ganglion cells (RGCs) is important for improving visual perception. This study investigates the use of high frequency stimulation (HFS) to elicit RGC activation, using a closed-loop algorithm to search for optimal stimulation parameters for preferential ON and OFF RGC activation, resembling natural physiological neural encoding in response to visual stimuli. We evaluated the performance of a wide range of electrical stimulation amplitudes and frequencies on RGC responses in vitro using murine retinal preparations. It was possible to preferentially excite either ON or OFF RGCs by adjusting amplitudes and frequencies in HFS. ON RGCs can be preferentially activated at relatively higher stimulation amplitudes (>150 μA) and frequencies (2–6.25 kHz) while OFF RGCs are activated by lower stimulation amplitudes (40–90 μA) across all tested frequencies (1–6.25 kHz). These stimuli also showed great promise in eliciting RGC responses that parallel natural RGC encoding: ON RGCs exhibited an increase in spiking activity during electrical stimulation while OFF RGCs exhibited decreased spiking activity, given the same stimulation amplitude. In conjunction with the in vitro studies, in silico simulations indicated that optimal HFS parameters could be rapidly identified in practice, whilst sampling spiking activity of relevant neuronal subtypes. This closed-loop approach represents a step forward in modulating stimulation parameters to achieve appropriate neural encoding in retinal prostheses, advancing control over RGC subtypes activated by electrical stimulation. PMID:29615857

Tickling the retina: integration of subthreshold electrical pulses can activate retinal neurons

NASA Astrophysics Data System (ADS)

Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

2016-08-01

Objective. The field of retinal prosthetics has made major progress over the last decade, restoring visual percepts to people suffering from retinitis pigmentosa. The stimulation pulses used by present implants are suprathreshold, meaning individual pulses are designed to activate the retina. In this paper we explore subthreshold pulse sequences as an alternate stimulation paradigm. Subthreshold pulses have the potential to address important open problems such as fading of visual percepts when patients are stimulated at moderate pulse repetition rates and the difficulty in preferentially stimulating different retinal pathways. Approach. As a first step in addressing these issues we used Gaussian white noise electrical stimulation combined with spike-triggered averaging to interrogate whether a subthreshold sequence of pulses can be used to activate the mouse retina. Main results. We demonstrate that the retinal network can integrate multiple subthreshold electrical stimuli under an experimental paradigm immediately relevant to retinal prostheses. Furthermore, these characteristic stimulus sequences varied in their shape and integration window length across the population of retinal ganglion cells. Significance. Because the subthreshold sequences activate the retina at stimulation rates that would typically induce strong fading (25 Hz), such retinal ‘tickling’ has the potential to minimize the fading problem. Furthermore, the diversity found across the cell population in characteristic pulse sequences suggests that these sequences could be used to selectively address the different retinal pathways (e.g. ON versus OFF). Both of these outcomes may significantly improve visual perception in retinal implant patients.

Deep-tissue reporter-gene imaging with fluorescence and optoacoustic tomography: a performance overview.

PubMed

Deliolanis, Nikolaos C; Ale, Angelique; Morscher, Stefan; Burton, Neal C; Schaefer, Karin; Radrich, Karin; Razansky, Daniel; Ntziachristos, Vasilis

2014-10-01

A primary enabling feature of near-infrared fluorescent proteins (FPs) and fluorescent probes is the ability to visualize deeper in tissues than in the visible. The purpose of this work is to find which is the optimal visualization method that can exploit the advantages of this novel class of FPs in full-scale pre-clinical molecular imaging studies. Nude mice were stereotactically implanted with near-infrared FP expressing glioma cells to from brain tumors. The feasibility and performance metrics of FPs were compared between planar epi-illumination and trans-illumination fluorescence imaging, as well as to hybrid Fluorescence Molecular Tomography (FMT) system combined with X-ray CT and Multispectral Optoacoustic (or Photoacoustic) Tomography (MSOT). It is shown that deep-seated glioma brain tumors are possible to visualize both with fluorescence and optoacoustic imaging. Fluorescence imaging is straightforward and has good sensitivity; however, it lacks resolution. FMT-XCT can provide an improved rough resolution of ∼1 mm in deep tissue, while MSOT achieves 0.1 mm resolution in deep tissue and has comparable sensitivity. We show imaging capacity that can shift the visualization paradigm in biological discovery. The results are relevant not only to reporter gene imaging, but stand as cross-platform comparison for all methods imaging near infrared fluorescent contrast agents.

Improving Empathy and Communication Skills of Visually Impaired Early Adolescents through a Psycho-Education Program

ERIC Educational Resources Information Center

Yildiz, Mehmet Ali; Duy, Baki

2013-01-01

The purpose of this study was to investigate the effectiveness of an interpersonal communication skills psycho-education program to improve empathy and communication skills of visually impaired adolescents. Participants of the study were sixteen early adolescents schooling in an elementary school for visually impaired youth in Diyarbakir. The…

From genes to brain oscillations: is the visual pathway the epigenetic clue to schizophrenia?

PubMed

González-Hernández, J A; Pita-Alcorta, C; Cedeño, I R

2006-01-01

Molecular data and gene expression data and recently mitochondrial genes and possible epigenetic regulation by non-coding genes is revolutionizing our views on schizophrenia. Genes and epigenetic mechanisms are triggered by cell-cell interaction and by external stimuli. A number of recent clinical and molecular observations indicate that epigenetic factors may be operational in the origin of the illness. Based on the molecular insights, gene expression profiles and epigenetic regulation of gene, we went back to the neurophysiology (brain oscillations) and found a putative role of the visual experiences (i.e. visual stimuli) as epigenetic factor. The functional evidences provided here, establish a direct link between the striate and extrastriate unimodal visual cortex and the neurobiology of the schizophrenia. This result support the hypothesis that 'visual experience' has a potential role as epigenetic factor and contribute to trigger and/or to maintain the progression of the schizophrenia. In this case, candidate genes sensible for the visual 'insult' may be located within the visual cortex including associative areas, while the integrity of the visual pathway before reaching the primary visual cortex is preserved. The same effect can be perceived if target genes are localised within the visual pathway, which actually, is more sensitive for 'insult' during the early life than the cortex per se. If this process affects gene expression at these sites a stably sensory specific 'insult', i.e. distorted visual information, is entering the visual system and expanded to fronto-temporo-parietal multimodal areas even from early maturation periods. The difference in the timing of postnatal neuroanatomical events between such areas and the primary visual cortex in humans (with the formers reaching the same development landmarks later in life than the latter) is 'optimal' to establish an abnormal 'cell- communication' mediated by the visual system that may further interfere with the local physiology. In this context the strategy to search target genes need to be rearrangement and redirected to visual-related genes. Otherwise, psychophysics studies combining functional neuroimage, and electrophysiology are strongly recommended, for the search of epigenetic clues that will allow to carrier gene association studies in schizophrenia.

Neural basis of imprinting behavior in chicks.

PubMed

Nakamori, Tomoharu; Maekawa, Fumihiko; Sato, Katsushige; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

2013-01-01

Newly hatched chicks memorize the characteristics of the first moving object they encounter, and subsequently show a preference for it. This "imprinting" behavior is an example of infant learning and is elicited by visual and/or auditory cues. Visual information of imprinting stimuli in chicks is first processed in the visual Wulst (VW), a telencephalic area corresponding to the mammalian visual cortex, congregates in the core region of the hyperpallium densocellulare (HDCo) cells, and transmitted to the intermediate medial mesopallium (IMM), a region similar to the mammalian association cortex. The imprinting memory is stored in the IMM, and activities of IMM neurons are altered by imprinting. Imprinting also induces functional and structural plastic changes of neurons in the circuit that links the VW and the IMM. Of these neurons, the activity of the HDCo cells is strongly influenced by imprinting. Expression and modulation of NR2B subunit-containing N-methyl-D-aspartate (NMDA) receptors in the HDCo cells are crucial for plastic changes in this circuit as well as the process of visual imprinting. Thus, elucidation of cellular and molecular mechanisms underlying the plastic changes that occurred in the HDCo cells may provide useful knowledge about infant learning. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

Perceptual learning improves contrast sensitivity, visual acuity, and foveal crowding in amblyopia.

PubMed

Barollo, Michele; Contemori, Giulio; Battaglini, Luca; Pavan, Andrea; Casco, Clara

2017-01-01

Amblyopic observers present abnormal spatial interactions between a low-contrast sinusoidal target and high-contrast collinear flankers. It has been demonstrated that perceptual learning (PL) can modulate these low-level lateral interactions, resulting in improved visual acuity and contrast sensitivity. We measured the extent and duration of generalization effects to various spatial tasks (i.e., visual acuity, Vernier acuity, and foveal crowding) through PL on the target's contrast detection. Amblyopic observers were trained on a contrast-detection task for a central target (i.e., a Gabor patch) flanked above and below by two high-contrast Gabor patches. The pre- and post-learning tasks included lateral interactions at different target-to-flankers separations (i.e., 2, 3, 4, 8λ) and included a range of spatial frequencies and stimulus durations as well as visual acuity, Vernier acuity, contrast-sensitivity function, and foveal crowding. The results showed that perceptual training reduced the target's contrast-detection thresholds more for the longest target-to-flanker separation (i.e., 8λ). We also found generalization of PL to different stimuli and tasks: contrast sensitivity for both trained and untrained spatial frequencies, visual acuity for Sloan letters, and foveal crowding, and partially for Vernier acuity. Follow-ups after 5-7 months showed not only complete maintenance of PL effects on visual acuity and contrast sensitivity function but also further improvement in these tasks. These results suggest that PL improves facilitatory lateral interactions in amblyopic observers, which usually extend over larger separations than in typical foveal vision. The improvement in these basic visual spatial operations leads to a more efficient capability of performing spatial tasks involving high levels of visual processing, possibly due to the refinement of bottom-up and top-down networks of visual areas.

Young donor-graft assisted endothelial keratoplasty (PDEK/DMEK) with epithelial debridement for chronic pseudophakic bullous keratopathy.

PubMed

Agarwal, Amar; Narang, Priya; Kumar, Dhivya A; Agarwal, Ashvin

2017-10-01

The aim of this study was to describe the applicability and report visual outcomes for the treatment of subepithelial fibrosis and anterior stromal scarring in cases of chronic pseudophakic bullous keratopathy (PBK) with epithelial debridement and endothelial keratoplasty (EK) (pre-Descemet endothelial keratoplasty [PDEK]; Descemet membrane endothelial keratoplasty [(DMEK]) using young donor tissue. Prospective, single-centre, interventional study. 6 cases with chronic PBK (> 1 year duration). Case 1 underwent PDEK with glued intraocular lens (IOL) as a single-stage procedure, whereas cases 2 and 3 underwent glued IOL followed by DMEK and PDEK, respectively, as a second-stage procedure. Cases 4 and 6 underwent PDEK, whereas case 5 underwent DMEK. Epithelial debridement was performed in all cases at the time of EK, and young donor grafts were used. The main outcome measures were best spectacle-corrected visual acuity, clearance of corneal scar and haze, central corneal thickness (CCT), specular microscopy, and endothelial cell count (ECC). Postoperatively, all cases demonstrated significant improvement in visual acuity. The mean value of depth of subepithelial haze was 121±71.7 µm and 25.3 ± 19.8 µm in the preoperative and postoperative periods, respectively (p = 0.028). At the 1-month follow-up, the mean preoperative CCT of 676 ± 92.7 µm was reduced to 534.6 ± 21.1µm. At the 6-month follow-up, the mean ECC loss resulting from the procedure was 36.5 ± 10.4%. EK with epithelial debridement performed for the treatment of chronic PBK resulted in significantly improved visual acuity to a functional level, with the clearance of subepithelial fibrosis and anterior stromal scar, in most patients. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Advanced cardiac chemical exchange saturation transfer (cardioCEST) MRI for in vivo cell tracking and metabolic imaging

PubMed Central

Pumphrey, Ashley; Yang, Zhengshi; Ye, Shaojing; Powell, David K.; Thalman, Scott; Watt, David S.; Abdel-Latif, Ahmed; Unrine, Jason; Thompson, Katherine; Fornwalt, Brandon; Ferrauto, Giuseppe; Vandsburger, Moriel

2016-01-01

An improved pre-clinical cardiac chemical exchange saturation transfer (CEST) pulse sequence (cardioCEST) was used to selectively visualize paramagnetic CEST (paraCEST)-labeled cells following intramyocardial implantation. In addition, cardioCEST was used to examine the effect of diet-induced obesity upon myocardial creatine CEST contrast. CEST pulse sequences were designed from standard turbo-spin-echo and gradient-echo sequences, and a cardiorespiratory-gated steady-state cine gradient-echo sequence. In vitro validation studies performed in phantoms composed of 20mM Eu-HPDO3A, 20mM Yb-HPDO3A, or saline demonstrated similar CEST contrast by spin-echo and gradient-echo pulse sequences. Skeletal myoblast cells (C2C12) were labeled with either Eu-HPDO3A or saline using a hypotonic swelling procedure and implanted into the myocardium of C57B6/J mice. Inductively coupled plasma mass spectrometry confirmed cellular levels of Eu of 2.1 × 10−3 ng/cell in Eu-HPDO3A-labeled cells and 2.3 × 10−5 ng/cell in saline-labeled cells. In vivo cardioCEST imaging of labeled cells at ±15ppm was performed 24 h after implantation and revealed significantly elevated asymmetric magnetization transfer ratio values in regions of Eu-HPDO3A-labeled cells when compared with surrounding myocardium or saline-labeled cells. We further utilized the cardioCEST pulse sequence to examine changes in myocardial creatine in response to diet-induced obesity by acquiring pairs of cardioCEST images at ±1.8 ppm. While ventricular geometry and function were unchanged between mice fed either a high-fat diet or a corresponding control low-fat diet for 14 weeks, myocardial creatine CEST contrast was significantly reduced in mice fed the high-fat diet. The selective visualization of paraCEST-labeled cells using cardioCEST imaging can enable investigation of cell fate processes in cardioregenerative medicine, or multiplex imaging of cell survival with imaging of cardiac structure and function and additional imaging of myocardial creatine. PMID:26684053

Neurorehabilitation of saccadic ocular movement in a patient with a homonymous hemianopia postgeniculate caused by an arteriovenous malformation

PubMed Central

Pineda-Ortíz, Mirna; Pacheco-López, Gustavo; Rubio-Osornio, Moisés; Rubio, Carmen; Valadez-Rodríguez, Juan

2018-01-01

Abstract Rationale: Visual therapy, which includes a restorative and compensatory approach, seems to be a viable treatment option for homonymous defects of the visual field in patients with postgeniculate injury of the visual pathway, due to occipital arteriovenous malformation (AVM). Until now, the Mexican population suffering from homonymous hemianopia did not have health services that provided any type of visual therapy for their condition. Patient concerns: A 31-year-old patient, who underwent a surgical procedure for resection of the AVM, was referred with posterior low vision on the left side. Diagnoses: The patient was diagnosed with left homonymous hemianopia. Interventions: Visual neurorehabilitation therapy (NRT), which integrated restorative and compensatory approaches, was administered for 3 hours each week. NRT included fixation, follow-up, search, peripheral vision, and reading. Outcomes: The NRT did not change visual field defects and, retinotopocally, the same campimetric defects remained. However, after training the tracking ocular movements improved to standard values on the ENG, further, the visual search became more organized. The reading reached a level without mistakes, with rhythm and goog intonation. The Beck test demostrated an improvement in depression symptoms. Regarding the daily life activities, the patient reported significant improvements. Lessons: Visual NRT can significantly improve eye movements, as well as the quality of life and independence of the patient. This integral approach could be an effective therapeutic option for homonymous defects of the visual field. PMID:29538218

Functional Visual Improvement After Cataract Surgery in Eyes With Age-Related Macular Degeneration: Results of the Ophthalmic Surgical Outcomes Data Project.

PubMed

Stock, Michael V; Vollman, David E; Baze, Elizabeth F; Chomsky, Amy S; Daly, Mary K; Lawrence, Mary G

2015-04-01

To determine if cataract surgery on eyes with AMD confers as much functional visual improvement as surgery on eyes without retinal pathology. This is a retrospective analysis of 4924 cataract surgeries from the Veterans Healthcare Administration Ophthalmic Surgical Outcomes Data Project (OSOD). We included cases of eyes with AMD that had both preoperative and postoperative NEI-VFQ-25 questionnaires submitted and compared their outcomes with controls without retinal pathology. We excluded patients with other retinal pathologies (740 patients). The analyses compared changes in visual acuity and overall functional visual improvement and its subscales using t-tests, multivariate logistic regressions, and linear regression modeling. Preoperative and postoperative questionnaires were submitted by 58.3% of AMD and 63.8% of no retinal pathology cases (controls). Analysis of overall score showed that cataract surgery on eyes with AMD led to increased visual function (13.8 ± 2.4 NEI-VFQ units, P < 0.0001); however, increases were significantly less when compared with controls (-6.4 ± 2.9 NEI-VFQ units, P < 0.0001). Preoperative best-corrected visual acuity (preBCVA) in AMD was predictive of postoperative visual function (r = -0.38, P < 0.0001). In controls, postoperative visual function was only weakly associated with preBCVA (r = -0.075, P = 0.0002). Patients with AMD with vision of 20/40 or better had overall outcomes similar to controls (-2.2 ± 4.7 NEI-VFQ units, P = 0.37). Cataract surgery on eyes with AMD offers an increase in functional visual improvement; however, the amount of benefit is associated with the eye's preBCVA. For eyes with preBCVA of 20/40 or greater, the improvement is similar to that of patients without retinal pathology. However, if preBCVA is less than 20/40, the amount of improvement was shown to be significantly less and decreased with decreasing preBCVA.

[Association between visual improvement after photocoagulation and the use of angiotensin converting enzyme inhibitors in diabetic macular oedema].

PubMed

Somilleda-Ventura, Selma Alin; García-Rubio, Yatzul Zuhaila; Razo Blanco-Hernández, Dulce Milagros; Lima-Gómez, Virgilio

2016-01-01

Angiotensin converting enzyme inhibitors are effective in delaying the progression of diabetic retinopathy. It is unknown if their use is associated with a better visual outcome in patients with diabetic macular oedema. A non-experimental, comparative, longitudinal and retrospective study was performed on patients with diabetic macular oedema treated by focal photocoagulation, and with systemic arterial hypertension treated with angiotensin converting enzyme inhibitors (Group 1), and without hypertension (Group 2). The dependent variable was the proportion with visual improvement, operatively defined as the gain of one or more lines of vision three weeks after photocoagulation. The independent variable was the use of angiotensin converting enzyme inhibitors. The proportion of eyes with visual improvement after treatment was compared between groups using the Chi squared (χ(2)) test. A total of 33 eyes (51.6%) were assigned to group 1, and 31 (48.2%), to group 2. The mean of visual acuity improved after three weeks, compared with baseline (p=0.002). The proportion of eyes with visual improvement did not differ between patients treated with angiotensin converting enzyme inhibitors (45.5%) and those that did not use them (51.6%, p=0.4). There was no statistical difference in the proportion of eyes with visual improvement between patients treated with angiotensin converting enzyme inhibitors and in those where they were not used. There is no support for the inhibition of angiotensin II in addition to photocoagulation for improving the outcome in patients with diabetic macular oedema. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Visual Prosthesis: Interfacing Stimulating Electrodes with Retinal Neurons to Restore Vision

PubMed Central

Barriga-Rivera, Alejandro; Bareket, Lilach; Goding, Josef; Aregueta-Robles, Ulises A.; Suaning, Gregg J.

2017-01-01

The bypassing of degenerated photoreceptors using retinal neurostimulators is helping the blind to recover functional vision. Researchers are investigating new ways to improve visual percepts elicited by these means as the vision produced by these early devices remain rudimentary. However, several factors are hampering the progression of bionic technologies: the charge injection limits of metallic electrodes, the mechanical mismatch between excitable tissue and the stimulating elements, neural and electric crosstalk, the physical size of the implanted devices, and the inability to selectively activate different types of retinal neurons. Electrochemical and mechanical limitations are being addressed by the application of electromaterials such as conducting polymers, carbon nanotubes and nanocrystalline diamonds, among other biomaterials, to electrical neuromodulation. In addition, the use of synthetic hydrogels and cell-laden biomaterials is promising better interfaces, as it opens a door to establishing synaptic connections between the electrode material and the excitable cells. Finally, new electrostimulation approaches relying on the use of high-frequency stimulation and field overlapping techniques are being developed to better replicate the neural code of the retina. All these elements combined will bring bionic vision beyond its present state and into the realm of a viable, mainstream therapy for vision loss. PMID:29184478

Preparation of wholemount mouse intestine for high-resolution three-dimensional imaging using two-photon microscopy.

PubMed

Appleton, P L; Quyn, A J; Swift, S; Näthke, I

2009-05-01

Visualizing overall tissue architecture in three dimensions is fundamental for validating and integrating biochemical, cell biological and visual data from less complex systems such as cultured cells. Here, we describe a method to generate high-resolution three-dimensional image data of intact mouse gut tissue. Regions of highest interest lie between 50 and 200 mum within this tissue. The quality and usefulness of three-dimensional image data of tissue with such depth is limited owing to problems associated with scattered light, photobleaching and spherical aberration. Furthermore, the highest-quality oil-immersion lenses are designed to work at a maximum distance of

a Mapping Method of Slam Based on Look up Table

NASA Astrophysics Data System (ADS)

Wang, Z.; Li, J.; Wang, A.; Wang, J.

2017-09-01

In the last years several V-SLAM(Visual Simultaneous Localization and Mapping) approaches have appeared showing impressive reconstructions of the world. However these maps are built with far more than the required information. This limitation comes from the whole process of each key-frame. In this paper we present for the first time a mapping method based on the LOOK UP TABLE(LUT) for visual SLAM that can improve the mapping effectively. As this method relies on extracting features in each cell divided from image, it can get the pose of camera that is more representative of the whole key-frame. The tracking direction of key-frames is obtained by counting the number of parallax directions of feature points. LUT stored all mapping needs the number of cell corresponding to the tracking direction which can reduce the redundant information in the key-frame, and is more efficient to mapping. The result shows that a better map with less noise is build using less than one-third of the time. We believe that the capacity of LUT efficiently building maps makes it a good choice for the community to investigate in the scene reconstruction problems.

Neuropsychological Profile of a Girl with Wiskott-Aldrich Syndrome.

PubMed

Byrne, Andrea M; Schechter, Tal; Westmacott, Robyn

2018-03-01

We report the neuropsychological profile of a 6-year-old girl with Wiskott-Aldrich syndrome, a rare X-linked immunodeficiency disorder associated with thrombocytopenia, eczema, recurrent infections, and malignancy. Wiskott-Aldrich syndrome occurs almost exclusively in males and is extremely rare in females, with no known research focused on cognitive and academic functioning in this population. Our patient was referred due to concerns about her memory and academic functioning. She had a history of progressive thrombocytopenia and hematopoietic stem cell transplantation at age 15 months. Standardized measures of intellectual ability, language, visual-spatial and visual-motor skills, attention, memory, and academic achievement were administered. The results showed average to above-average performance in multiple areas of cognitive and academic functioning, with weaknesses in phonological awareness and rapid naming. The advent of hematopoietic stem cell transplantation has led to considerable improvement in the long-term prognosis of children with Wiskott-Aldrich syndrome. Although the impact of this syndrome and related conditions on neurocognitive development is presently unknown, this case highlights both the importance of considering base rates for commonly occurring conditions and the significant role neuropsychology can play in identifying cognitive strengths and weaknesses in the context of the developing brain.

Multicolor microRNA FISH effectively differentiates tumor types

PubMed Central

Renwick, Neil; Cekan, Pavol; Masry, Paul A.; McGeary, Sean E.; Miller, Jason B.; Hafner, Markus; Li, Zhen; Mihailovic, Aleksandra; Morozov, Pavel; Brown, Miguel; Gogakos, Tasos; Mobin, Mehrpouya B.; Snorrason, Einar L.; Feilotter, Harriet E.; Zhang, Xiao; Perlis, Clifford S.; Wu, Hong; Suárez-Fariñas, Mayte; Feng, Huichen; Shuda, Masahiro; Moore, Patrick S.; Tron, Victor A.; Chang, Yuan; Tuschl, Thomas

2013-01-01

MicroRNAs (miRNAs) are excellent tumor biomarkers because of their cell-type specificity and abundance. However, many miRNA detection methods, such as real-time PCR, obliterate valuable visuospatial information in tissue samples. To enable miRNA visualization in formalin-fixed paraffin-embedded (FFPE) tissues, we developed multicolor miRNA FISH. As a proof of concept, we used this method to differentiate two skin tumors, basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC), with overlapping histologic features but distinct cellular origins. Using sequencing-based miRNA profiling and discriminant analysis, we identified the tumor-specific miRNAs miR-205 and miR-375 in BCC and MCC, respectively. We addressed three major shortcomings in miRNA FISH, identifying optimal conditions for miRNA fixation and ribosomal RNA (rRNA) retention using model compounds and high-pressure liquid chromatography (HPLC) analyses, enhancing signal amplification and detection by increasing probe-hapten linker lengths, and improving probe specificity using shortened probes with minimal rRNA sequence complementarity. We validated our method on 4 BCC and 12 MCC tumors. Amplified miR-205 and miR-375 signals were normalized against directly detectable reference rRNA signals. Tumors were classified using predefined cutoff values, and all were correctly identified in blinded analysis. Our study establishes a reliable miRNA FISH technique for parallel visualization of differentially expressed miRNAs in FFPE tumor tissues. PMID:23728175

Visual training improves perceptual grouping based on basic stimulus features.

PubMed

Kurylo, Daniel D; Waxman, Richard; Kidron, Rachel; Silverstein, Steven M

2017-10-01

Training on visual tasks improves performance on basic and higher order visual capacities. Such improvement has been linked to changes in connectivity among mediating neurons. We investigated whether training effects occur for perceptual grouping. It was hypothesized that repeated engagement of integration mechanisms would enhance grouping processes. Thirty-six participants underwent 15 sessions of training on a visual discrimination task that required perceptual grouping. Participants viewed 20 × 20 arrays of dots or Gabor patches and indicated whether the array appeared grouped as vertical or horizontal lines. Across trials stimuli became progressively disorganized, contingent upon successful discrimination. Four visual dimensions were examined, in which grouping was based on similarity in luminance, color, orientation, and motion. Psychophysical thresholds of grouping were assessed before and after training. Results indicate that performance in all four dimensions improved with training. Training on a control condition, which paralleled the discrimination task but without a grouping component, produced no improvement. In addition, training on only the luminance and orientation dimensions improved performance for those conditions as well as for grouping by color, on which training had not occurred. However, improvement from partial training did not generalize to motion. Results demonstrate that a training protocol emphasizing stimulus integration enhanced perceptual grouping. Results suggest that neural mechanisms mediating grouping by common luminance and/or orientation contribute to those mediating grouping by color but do not share resources for grouping by common motion. Results are consistent with theories of perceptual learning emphasizing plasticity in early visual processing regions.

Photoreceptor Cells With Profound Structural Deficits Can Support Useful Vision in Mice

PubMed Central

Thompson, Stewart; Blodi, Frederick R.; Lee, Swan; Welder, Chris R.; Mullins, Robert F.; Tucker, Budd A.; Stasheff, Steven F.; Stone, Edwin M.

2014-01-01

Purpose. In animal models of degenerative photoreceptor disease, there has been some success in restoring photoreception by transplanting stem cell–derived photoreceptor cells into the subretinal space. However, only a small proportion of transplanted cells develop extended outer segments, considered critical for photoreceptor cell function. The purpose of this study was to determine whether photoreceptor cells that lack a fully formed outer segment could usefully contribute to vision. Methods. Retinal and visual function was tested in wild-type and Rds mice at 90 days of age (RdsP90). Photoreceptor cells of mice homozygous for the Rds mutation in peripherin 2 never develop a fully formed outer segment. The electroretinogram and multielectrode recording of retinal ganglion cells were used to test retinal responses to light. Three distinct visual behaviors were used to assess visual capabilities: the optokinetic tracking response, the discrimination-based visual water task, and a measure of the effect of vision on wheel running. Results. RdsP90 mice had reduced but measurable electroretinogram responses to light, and exhibited light-evoked responses in multiple types of retinal ganglion cells, the output neurons of the retina. In optokinetic and discrimination-based tests, acuity was measurable but reduced, most notably when contrast was decreased. The wheel running test showed that RdsP90 mice needed 3 log units brighter luminance than wild type to support useful vision (10 cd/m2). Conclusions. Photoreceptors that lack fully formed outer segments can support useful vision. This challenges the idea that normal cellular structure needs to be completely reproduced for transplanted cells to contribute to useful vision. PMID:24569582

CXCR1 remodels the vascular niche to promote hematopoietic stem and progenitor cell engraftment

PubMed Central

Blaser, Bradley W.; Moore, Jessica L.; Hagedorn, Elliott J.; Li, Brian; Riquelme, Raquel; Yang, Song; Zhou, Yi; Tamplin, Owen J.; Binder, Vera

2017-01-01

The microenvironment is an important regulator of hematopoietic stem and progenitor cell (HSPC) biology. Recent advances marking fluorescent HSPCs have allowed exquisite visualization of HSPCs in the caudal hematopoietic tissue (CHT) of the developing zebrafish. Here, we show that the chemokine cxcl8 and its receptor, cxcr1, are expressed by zebrafish endothelial cells, and we identify cxcl8/cxcr1 signaling as a positive regulator of HSPC colonization. Single-cell tracking experiments demonstrated that this is a result of increases in HSPC–endothelial cell “cuddling,” HSPC residency time within the CHT, and HSPC mitotic rate. Enhanced cxcl8/cxcr1 signaling was associated with an increase in the volume of the CHT and induction of cxcl12a expression. Finally, using parabiotic zebrafish, we show that cxcr1 acts HSPC nonautonomously to improve the efficiency of donor HSPC engraftment. This work identifies a mechanism by which the hematopoietic niche remodels to promote HSPC engraftment and suggests that cxcl8/cxcr1 signaling is a potential therapeutic target in patients undergoing hematopoietic stem cell transplantation. PMID:28351983

Seeing in the dark: vision and visual behaviour in nocturnal bees and wasps.

PubMed

Warrant, Eric J

2008-06-01

In response to the pressures of predation, parasitism and competition for limited resources, several groups of (mainly) tropical bees and wasps have independently evolved a nocturnal lifestyle. Like their day-active (diurnal) relatives, these insects possess apposition compound eyes, a relatively light-insensitive eye design that is best suited to vision in bright light. Despite this, nocturnal bees and wasps are able to forage at night, with many species capable of flying through a dark and complex forest between the nest and a foraging site, a behaviour that relies heavily on vision and is limited by light intensity. In the two best-studied species - the Central American sweat bee Megalopta genalis (Halictidae) and the Indian carpenter bee Xylocopa tranquebarica (Apidae) - learned visual landmarks are used to guide foraging and homing. Their apposition eyes, however, have only around 30 times greater optical sensitivity than the eyes of their closest diurnal relatives, a fact that is apparently inconsistent with their remarkable nocturnal visual abilities. Moreover, signals generated in the photoreceptors, even though amplified by a high transduction gain, are too noisy and slow to transmit significant amounts of information in dim light. How have nocturnal bees and wasps resolved these paradoxes? Even though this question remains to be answered conclusively, a mounting body of theoretical and experimental evidence suggests that the slow and noisy visual signals generated by the photoreceptors are spatially summed by second-order monopolar cells in the lamina, a process that could dramatically improve visual reliability for the coarser and slower features of the visual world at night.

Diagnostic Clues to Human Herpesvirus 6 Encephalitis and Wernicke’s Encephalopathy after Pediatric Hematopoietic Cell Transplantation

PubMed Central

Sadighi, Zsila; Sabin, Noah D.; Hayden, Randall; Stewart, Elizabeth; Pillai, Asha

2015-01-01

Human herpesvirus 6 (HHV6) encephalitis and Wernicke’s encephalopathy are treatable yet frequently undiagnosed causes of encephalopathy in pediatric recipients of allogeneic and autologous hematopoietic cell transplantation. Here we review representative cases of both conditions to highlight specific and relevant neurologic features which prompted effective diagnosis and treatment. Two patients with confusion accompanied by seizures, memory changes, or specific visual hallucinations and HHV6 detectable by PCR in cerebrospinal fluid had improvement in viral load with ganciclovir or foscarnet treatment. Two patients had confusion, ataxia, or ocular changes and low serum thiamine levels, which resolved with parenteral thiamine. In all cases, definitive diagnosis and treatment were facilitated by a high index of suspicion and search for specific pathognomonic neurologic deficits accompanying the confusional state. It is critical to clinically differentiate these two conditions from other common neurologic syndromes occurring after transplant, allowing potentially improved patient outcomes by prompt diagnosis, and effective treatment. PMID:25564483

Targeted imaging of cancer by fluorocoxib C, a near-infrared cyclooxygenase-2 probe

NASA Astrophysics Data System (ADS)

Uddin, Md. Jashim; Crews, Brenda C.; Ghebreselasie, Kebreab; Daniel, Cristina K.; Kingsley, Philip J.; Xu, Shu; Marnett, Lawrence J.

2015-05-01

Cyclooxygenase-2 (COX-2) is a promising target for the imaging of cancer in a range of diagnostic and therapeutic settings. We report a near-infrared COX-2-targeted probe, fluorocoxib C (FC), for visualization of solid tumors by optical imaging. FC exhibits selective and potent COX-2 inhibition in both purified protein and human cancer cell lines. In vivo optical imaging shows selective accumulation of FC in COX-2-overexpressing human tumor xenografts [1483 head and neck squamous cell carcinoma (HNSCC)] implanted in nude mice, while minimal uptake is detectable in COX-2-negative tumor xenografts (HCT116) or 1483 HNSCC xenografts preblocked with the COX-2-selective inhibitor celecoxib. Time course imaging studies conducted from 3 h to 7-day post-FC injection revealed a marked reduction in nonspecific fluorescent signals with retention of fluorescence in 1483 HNSCC tumors. Thus, use of FC in a delayed imaging protocol offers an approach to improve imaging signal-to-noise that should improve cancer detection in multiple preclinical and clinical settings.

Cathode Wetting Studies in Magnesium Electrolysis

NASA Astrophysics Data System (ADS)

McLean, Kevin; Pettingill, James; Davis, Boyd

The effects of cathode materials and electrolyte additives on magnesium wetting were studied with the goal of improving current efficiency in a magnesium electrolysis cell. The study consisted of static wetting and electrolysis tests, both conducted in a visual cell with a molten salt electrolyte of MgCl2-CaCl2-NaCl-KCl-CaF2. The wetting conditions were tested using high resolution photography and contact angle software. The electrolysis tests were completed to qualitatively assess the effect of additives to the melt and were recorded with a digital video camcorder. Results from the static wetting tests showed a significant variation in wetting depending on the material used for the cathode. Mo and a Mo-W alloy, with contact angles of 60° and 52° respectively, demonstrated excellent wetting. The contact angle for steel was 132° and it ranged from 142°-154° for graphite depending on the type. Improvements to the cathode wetting were observed with tungsten and molybdenum oxide additives.

Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits.

PubMed

Xu, Hong-Ping; Burbridge, Timothy J; Ye, Meijun; Chen, Minggang; Ge, Xinxin; Zhou, Z Jimmy; Crair, Michael C

2016-03-30

Retinal waves are correlated bursts of spontaneous activity whose spatiotemporal patterns are critical for early activity-dependent circuit elaboration and refinement in the mammalian visual system. Three separate developmental wave epochs or stages have been described, but the mechanism(s) of pattern generation of each and their distinct roles in visual circuit development remain incompletely understood. We used neuroanatomical,in vitroandin vivoelectrophysiological, and optical imaging techniques in genetically manipulated mice to examine the mechanisms of wave initiation and propagation and the role of wave patterns in visual circuit development. Through deletion of β2 subunits of nicotinic acetylcholine receptors (β2-nAChRs) selectively from starburst amacrine cells (SACs), we show that mutual excitation among SACs is critical for Stage II (cholinergic) retinal wave propagation, supporting models of wave initiation and pattern generation from within a single retinal cell type. We also demonstrate that β2-nAChRs in SACs, and normal wave patterns, are necessary for eye-specific segregation. Finally, we show that Stage III (glutamatergic) retinal waves are not themselves necessary for normal eye-specific segregation, but elimination of both Stage II and Stage III retinal waves dramatically disrupts eye-specific segregation. This suggests that persistent Stage II retinal waves can adequately compensate for Stage III retinal wave loss during the development and refinement of eye-specific segregation. These experiments confirm key features of the "recurrent network" model for retinal wave propagation and clarify the roles of Stage II and Stage III retinal wave patterns in visual circuit development. Spontaneous activity drives early mammalian circuit development, but the initiation and patterning of activity vary across development and among modalities. Cholinergic "retinal waves" are initiated in starburst amacrine cells and propagate to retinal ganglion cells and higher-order visual areas, but the mechanism responsible for creating their unique and critical activity pattern is incompletely understood. We demonstrate that cholinergic wave patterns are dictated by recurrent connectivity within starburst amacrine cells, and retinal ganglion cells act as "readouts" of patterned activity. We also show that eye-specific segregation occurs normally without glutamatergic waves, but elimination of both cholinergic and glutamatergic waves completely disrupts visual circuit development. These results suggest that each retinal wave pattern during development is optimized for concurrently refining multiple visual circuits. Copyright © 2016 the authors 0270-6474/16/363872-16$15.00/0.

Differential encoding of spatial information among retinal on cone bipolar cells

PubMed Central

Purgert, Robert J.

2015-01-01

The retina is the first stage of visual processing. It encodes elemental features of visual scenes. Distinct cone bipolar cells provide the substrate for this to occur. They encode visual information, such as color and luminance, a principle known as parallel processing. Few studies have directly examined whether different forms of spatial information are processed in parallel among cone bipolar cells. To address this issue, we examined the spatial information encoded by mouse ON cone bipolar cells, the subpopulation excited by increments in illumination. Two types of spatial processing were identified. We found that ON cone bipolar cells with axons ramifying in the central inner plexiform layer were tuned to preferentially encode small stimuli. By contrast, ON cone bipolar cells with axons ramifying in the proximal inner plexiform layer, nearest the ganglion cell layer, were tuned to encode both small and large stimuli. This dichotomy in spatial tuning is attributable to amacrine cells providing stronger inhibition to central ON cone bipolar cells compared with proximal ON cone bipolar cells. Furthermore, background illumination altered this difference in spatial tuning. It became less pronounced in bright light, as amacrine cell-driven inhibition became pervasive among all ON cone bipolar cells. These results suggest that differential amacrine cell input determined the distinct spatial encoding properties among ON cone bipolar cells. These findings enhance the known parallel processing capacity of the retina. PMID:26203104

Optimizing wavefront-guided corrections for highly aberrated eyes in the presence of registration uncertainty

PubMed Central

Shi, Yue; Queener, Hope M.; Marsack, Jason D.; Ravikumar, Ayeswarya; Bedell, Harold E.; Applegate, Raymond A.

2013-01-01

Dynamic registration uncertainty of a wavefront-guided correction with respect to underlying wavefront error (WFE) inevitably decreases retinal image quality. A partial correction may improve average retinal image quality and visual acuity in the presence of registration uncertainties. The purpose of this paper is to (a) develop an algorithm to optimize wavefront-guided correction that improves visual acuity given registration uncertainty and (b) test the hypothesis that these corrections provide improved visual performance in the presence of these uncertainties as compared to a full-magnitude correction or a correction by Guirao, Cox, and Williams (2002). A stochastic parallel gradient descent (SPGD) algorithm was used to optimize the partial-magnitude correction for three keratoconic eyes based on measured scleral contact lens movement. Given its high correlation with logMAR acuity, the retinal image quality metric log visual Strehl was used as a predictor of visual acuity. Predicted values of visual acuity with the optimized corrections were validated by regressing measured acuity loss against predicted loss. Measured loss was obtained from normal subjects viewing acuity charts that were degraded by the residual aberrations generated by the movement of the full-magnitude correction, the correction by Guirao, and optimized SPGD correction. Partial-magnitude corrections optimized with an SPGD algorithm provide at least one line improvement of average visual acuity over the full magnitude and the correction by Guirao given the registration uncertainty. This study demonstrates that it is possible to improve the average visual acuity by optimizing wavefront-guided correction in the presence of registration uncertainty. PMID:23757512

Improving visual observation skills through the arts to aid radiographic interpretation in veterinary practice: A pilot study.

PubMed

Beck, Cathy; Gaunt, Heather; Chiavaroli, Neville

2017-09-01

Radiographic interpretation is a perceptual and cognitive skill. Recently core veterinary radiology textbooks have focused on the cognitive (i.e., the clinical aspects of radiographic interpretation) rather than the features of visual observation that improve identification of abnormalities. As a result, the skill of visual observation is underemphasized and thus often underdeveloped by trainees. The study of the arts in medical education has been used to train and improve visual observation and empathy. The use of the arts to improve visual observation skills in Veterinary Science has not been previously described. Objectives of this pilot study were to adapt the existing Visual Arts in Health Education Program for medical and dental students at the University of Melbourne, Australia to third year Doctor of Veterinary Medicine students and evaluate their perceptions regarding the program's effects on visual observation skills and confidence with respect to radiographic interpretation. This adaptation took the form of a single seminar given to third year Doctor of Veterinary Medicine students. Following the seminar, students reported an improved approach to radiographic interpretation and felt they had gained skills which would assist them throughout their career. In the year following the seminar, written reports of the students who attended the seminar were compared with reports from a matched cohort of students who did not attend the seminar. This demonstrated increased identification of abnormalities and greater description of the abnormalities identified. Findings indicated that explicit training in visual observation may be a valuable adjunct to the radiology training of Doctor of Veterinary Medicine students. © 2017 American College of Veterinary Radiology.

Vision restoration through extrastriate stimulation in patients with visual field defects: a double-blind and randomized experimental study.

PubMed

Jobke, Sandra; Kasten, Erich; Sabel, Bernhard A

2009-01-01

. Vision restoration therapy (VRT) to treat visual field defects used single-point visual stimulation in areas of residual vision up to now. The question arises if the efficiency of restoration can be increased when the entire region of blindness is trained by a visual stimulus aimed at activating extrastriate pathways (extrastriate VRT). . In this crossover study, 18 patients with visual field defects with prior VRT experience were treated with 2 training paradigms. Group 1 (n = 8) first used extrastriate VRT followed by conventional standard VRT. Group 2 (n = 10) trained in reverse order. Visual field size was assessed with computer-based perimetry and subjective vision with the National Eye Institute Visual Function Questionnaire (NEI-VFQ). . In group 1, stimulus detection in high-resolution perimetry (HRP) improved by 5.9% (P < .01) after extrastriate VRT. After the second training period (standard VRT), detection further improved by 1.8% (P = .093). In group 2, detection performance improved after standard VRT by 2.9% (P < .05) and after extrastriate VRT by 2.9% (P < .05). Detection performance increased twice as much after extrastriate VRT (4.2%) than after standard VRT (2.4%; P < .05). All changes in fixation performance were unrelated to detection improvements. NEI-VFQ did not show any significant changes. . Greater improvement after extrastriate VRT is interpreted as an activation of extrastriate pathways by massive "spiral-like" stimulation. These pathways bypass the damaged visual cortex, stimulating extrastriate cortical regions, and are thought to be involved in blindsight.

Examination of drivers' cell phone use behavior at intersections by using naturalistic driving data.

PubMed

Xiong, Huimin; Bao, Shan; Sayer, James; Kato, Kazuma

2015-09-01

Many driving simulator studies have shown that cell phone use while driving greatly degraded driving performance. In terms of safety analysis, many factors including drivers, vehicles, and driving situations need to be considered. Controlled or simulated studies cannot always account for the full effects of these factors, especially situational factors such as road condition, traffic density, and weather and lighting conditions. Naturalistic driving by its nature provides a natural and realistic way to examine drivers' behaviors and associated factors for cell phone use while driving. In this study, driving speed while using a cell phone (conversation or visual/manual tasks) was compared to two baselines (baseline 1: normal driving condition, which only excludes driving while using a cell phone, baseline 2: driving-only condition, which excludes all types of secondary tasks) when traversing an intersection. The outcomes showed that drivers drove slower when using a cell for both conversation and visual/manual (VM) tasks compared to baseline conditions. With regard to cell phone conversations, drivers were more likely to drive faster during the day time compared to night time driving and drive slower under moderate traffic compared to under sparse traffic situations. With regard to VM tasks, there was a significant interaction between traffic and cell phone use conditions. The maximum speed with VM tasks was significantly lower than that with baseline conditions under sparse traffic conditions. In contrast, the maximum speed with VM tasks was slightly higher than that with baseline driving under dense traffic situations. This suggests that drivers might self-regulate their behavior based on the driving situations and demand for secondary tasks, which could provide insights on driver distraction guidelines. With the rapid development of in-vehicle technology, the findings in this research could lead the improvement of human-machine interface (HMI) design as well. Copyright © 2015 Elsevier Ltd and National Safety Council. All rights reserved.

A computational model of the development of separate representations of facial identity and expression in the primate visual system.

PubMed

Tromans, James Matthew; Harris, Mitchell; Stringer, Simon Maitland

2011-01-01

Experimental studies have provided evidence that the visual processing areas of the primate brain represent facial identity and facial expression within different subpopulations of neurons. For example, in non-human primates there is evidence that cells within the inferior temporal gyrus (TE) respond primarily to facial identity, while cells within the superior temporal sulcus (STS) respond to facial expression. More recently, it has been found that the orbitofrontal cortex (OFC) of non-human primates contains some cells that respond exclusively to changes in facial identity, while other cells respond exclusively to facial expression. How might the primate visual system develop physically separate representations of facial identity and expression given that the visual system is always exposed to simultaneous combinations of facial identity and expression during learning? In this paper, a biologically plausible neural network model, VisNet, of the ventral visual pathway is trained on a set of carefully-designed cartoon faces with different identities and expressions. The VisNet model architecture is composed of a hierarchical series of four Self-Organising Maps (SOMs), with associative learning in the feedforward synaptic connections between successive layers. During learning, the network develops separate clusters of cells that respond exclusively to either facial identity or facial expression. We interpret the performance of the network in terms of the learning properties of SOMs, which are able to exploit the statistical indendependence between facial identity and expression.

Case Report: Use of Sports and Performance Vision Training to Benefit a Low-vision Patient's Function.

PubMed

Laby, Daniel M

2018-05-17

Despite our inability to attenuate the course of many ocular diseases that can ultimately lead to loss or significantly decreased visual function, this report describes a potential technique to aid such patients in maximizing the use of the vision that remains. The aim of this study was to demonstrate the applicability of utilizing sports vision training to improve objective and subjective visuomotor function in a low-vision patient. A 37-year-old woman with Usher syndrome presented with reduced central visual acuity and visual field. Although we were unable to reverse the damage resulting from her diagnosis, we were able to improve the use of the remaining vision. A 27 to 31% improvement in hand-eye coordination was achieved along with a 41% improvement in object tracking and visual concentration. Most importantly, following the 14-week training period, there was also a subjective improvement in the patient's appreciation of her visual ability. The sports vision literature cites many examples in which sports vision training is useful in improving visuomotor and on-field performance. We hypothesized that these techniques may be used to aid not only athletes but also patients with low vision. Despite suffering from reduced acuity and a limited visual field, these patients often still have a significant amount of vision ability that can be used to guide motor actions. Using techniques to increase the efficient use of this remaining vision may reduce the impact of the reduced visual function and aid in activities of daily living.

Arabidopsis Regenerating Protoplast: A Powerful Model System for Combining the Proteomics of Cell Wall Proteins and the Visualization of Cell Wall Dynamics

PubMed Central

Yokoyama, Ryusuke; Kuki, Hiroaki; Kuroha, Takeshi; Nishitani, Kazuhiko

2016-01-01

The development of a range of sub-proteomic approaches to the plant cell wall has identified many of the cell wall proteins. However, it remains difficult to elucidate the precise biological role of each protein and the cell wall dynamics driven by their actions. The plant protoplast provides an excellent means not only for characterizing cell wall proteins, but also for visualizing the dynamics of cell wall regeneration, during which cell wall proteins are secreted. It therefore offers a unique opportunity to investigate the de novo construction process of the cell wall. This review deals with sub-proteomic approaches to the plant cell wall through the use of protoplasts, a methodology that will provide the basis for further exploration of cell wall proteins and cell wall dynamics. PMID:28248244

Experimental study of CO2 dissolution a convection phenomenon at high pressure

NASA Astrophysics Data System (ADS)

Ben Salem, Imen; Chevalier, Sylvie; Faisal, Titly Farhana; Abderrahmane, Hamid; Sassi, Mohamed

2016-05-01

The density driven convection phenomenon has a significant role in enhancing the CO2 geological storage capacity. Deep saline aquifers are targeted for large scale geological sequestration. Once the CO2 is injected in saline aquifer, the supercritical CO2 rises up, forms a thin layer of free phase CO2, and the dissolution and molecular diffusion of the dissolved CO2 in brine begins. The CO2 saturated brine is denser than the original brine leading to gravitational convection of CO2 saturated brine. Convection accelerates the dissolution process and thus improves the safety and the efficiency of the sequestration. Laboratory experiments have been previously performed with experimental set-ups allowing the visualization of the phenomenon (1) eventually combined to the measurements of the dissolved CO2 mass transfer (2) as a function of the permeability of the medium. The visualization of the process was possible as Hele-Shaw cells at atmospheric pressure were used. Pressurized cylindrical vessel containing porous media allows measuring mass transfer of CO2 using the pressure decay concept (3) but visualization of the convection/dissolution was not possible for these setups. In this work, we performed experiments in a pressurized transparent cell similar to a Hele-Shaw cell but with bigger aperture. Permeability was varied by changing the size of the glass beads filling the cell. Bromocrysol green was used as a dye to track the pH change due to the presence of dissolved CO2 (1). The phenomenon is captured by a high resolution camera. We studied the effect of the pressure and of the permeability on the fingering pattern, the onset and the timescale of the phenomenon and the quantitative mass transfer of dissolved CO2. Experiments were validated on numerical simulations performed using STOMP (Subsurface Transport Over Multiple Phases) developed by the PNNL (Pacific Northwest National Laboratory) Hydrology group of the Department of Energy, USA. (1) Kneafsey, T.J., Pruess, K., 2010. Laboratory flow experiments for visualizing carbon dioxide-induced density-driven brine convection, Transport in Porous Media 82, 123-139. (2) Faisal, T. F., Chevalier, S., Bernabé, Y., Juanes, R. and M. Sassi. 2015. Quantitative and qualitative study of density driven CO2 mass transfer in a vertical Hele-Shaw cell. International Journal of Heat and Mass Transfer. Vol. 81, 901-914. (3) Farajzadeh, R.; Barati, A.; Delil, H. A.; Bruining, J.; Zitha, P. L. J., Mass transfer of CO2 into water and surfactant solutions, Petroleum Science and Technology 25 (12) (2007) 1493-1511.

M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer

NASA Astrophysics Data System (ADS)

Ghosh, Debadyuti; Lee, Youjin; Thomas, Stephanie; Kohli, Aditya G.; Yun, Dong Soo; Belcher, Angela M.; Kelly, Kimberly A.

2012-10-01

Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein-protein interactions, enzyme activity or gene expression. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and would improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection.

M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer.

PubMed

Ghosh, Debadyuti; Lee, Youjin; Thomas, Stephanie; Kohli, Aditya G; Yun, Dong Soo; Belcher, Angela M; Kelly, Kimberly A

2012-10-01

Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein-protein interactions, enzyme activity or gene expression. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and would improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection.

M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer

PubMed Central

Ghosh, Debadyuti; Lee, Youjin; Thomas, Stephanie; Kohli, Aditya G.; Yun, Dong Soo; Belcher, Angela M.; Kelly, Kimberly A.

2014-01-01

Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment1. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein-protein interactions, enzyme activity or gene expression2. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand3,4,5 and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells6. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection. PMID:22983492

Visual Acuity Improvement in Continuous vs Divided Occlusion in Anisometropic Amblyopia

PubMed Central

Irfani, Irawati; Feriyanto, Feri; Oktarima, Primawita; Kartasasmita, Arief

2018-01-01

Purpose: To compare visual acuity improvement between continuous and split part-time occlusion for the treatment of moderate and severe anisometropic amblyopia. Methods: Randomised clinical trials in 6 – 13 y.o children with moderate and severe anisometropic amblyopia. Each patient was consecutively selected with continuous or split part-time occlusion. Best corrected visual acuity’s improvement was followed up to six weeks and statistical data were analyzed using chi square and unpaired t-test. Results: Best corrected visual acuity’s improvement was comparable between continuous and split part-time occlusion (0.20±0.27 vs 0.21±0.25; p = 0.79). Conclusion: Split part-time occlusion may be considered as an alternative treatment for moderate and severe anisometropic amblyopia treatment. PMID:29515681

Beneficial effects of enriched environment following status epilepticus in immature rats.

PubMed

Faverjon, S; Silveira, D C; Fu, D D; Cha, B H; Akman, C; Hu, Y; Holmes, G L

2002-11-12

There is increasing evidence that enriching the environment can improve cognitive and motor deficits following a variety of brain injuries. Whether environmental enrichment can improve cognitive impairment following status epilepticus (SE) is not known. To determine whether the environment in which animals are raised influences cognitive function in normal rats and rats subjected to SE. Rats (n = 100) underwent lithium-pilocarpine-induced SE at postnatal (P) day 20 and were then placed in either an enriched environment consisting of a large play area with toys, climbing objects, and music, or in standard vivarium cages for 30 days. Control rats (n = 32) were handled similarly to the SE rats but received saline injections instead of lithium-pilocarpine. Rats were then tested in the water maze, a measure of visual-spatial memory. A subset of the rats were killed during exposure to the enriched or nonenriched environment and the brains examined for dentate granule cell neurogenesis using bromodeoxyuridine (BrdU) and phosphorylated cyclic AMP response element binding protein (pCREB) immunostaining, a brain transcription factor important in long-term memory. Both control and SE rats exposed to the enriched environment performed significantly better than the nonenriched group in the water maze. There was a significant increase in neurogenesis and pCREB immunostaining in the dentate gyrus in both control and SE animals exposed to the enriched environment compared to the nonenriched groups. Environmental enrichment resulted in no change in SE-induced histologic damage. Exposure to an enriched environment in weanling rats significantly improves visual-spatial learning. Even following SE, an enriched environment enhances cognitive function. An increase in neurogenesis and activation of transcription factors may contribute to this enhanced visual-spatial memory.

Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial.

PubMed

Kempen, John H; Van Natta, Mark L; Altaweel, Michael M; Dunn, James P; Jabs, Douglas A; Lightman, Susan L; Thorne, Jennifer E; Holbrook, Janet T

2015-12-01

To identify factors associated with best-corrected visual acuity (BCVA) presentation and 2-year outcome in 479 intermediate, posterior, and panuveitic eyes. Cohort study using randomized controlled trial data. Multicenter Uveitis Steroid Treatment (MUST) Trial masked BCVA measurements at baseline and at 2 years follow-up used gold-standard methods. Twenty-three clinical centers documented characteristics per protocol, which were evaluated as potential predictive factors for baseline BCVA and 2-year change in BCVA. Baseline factors significantly associated with reduced BCVA included age ≥50 vs <50 years; posterior vs intermediate uveitis; uveitis duration >10 vs <6 years; anterior chamber (AC) flare >grade 0; cataract; macular thickening; and exudative retinal detachment. Over 2 years, eyes better than 20/50 and 20/50 or worse at baseline improved, on average, by 1 letter (P = .52) and 10 letters (P < .001), respectively. Both treatment groups and all sites of uveitis improved similarly. Factors associated with improved BCVA included resolution of active AC cells, resolution of macular thickening, and cataract surgery in an initially cataractous eye. Factors associated with worsening BCVA included longer duration of uveitis (6-10 or >10 vs <6 years), incident AC flare, cataract at both baseline and follow-up, pseudophakia at baseline, persistence or incidence of vitreous haze, and incidence of macular thickening. Intermediate, posterior, and panuveitis have a similarly favorable prognosis with both systemic and fluocinolone acetonide implant treatment. Eyes with more prolonged/severe inflammatory damage and/or inflammatory findings initially or during follow-up have a worse visual acuity prognosis. The results indicate the value of implementing best practices in managing inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Advances in bioluminescence imaging: new probes from old recipes.

PubMed

Yao, Zi; Zhang, Brendan S; Prescher, Jennifer A

2018-06-04

Bioluminescent probes are powerful tools for visualizing biology in live tissues and whole animals. Recent years have seen a surge in the number of new luciferases, luciferins, and related tools available for bioluminescence imaging. Many were crafted using classic methods of optical probe design and engineering. Here we highlight recent advances in bioluminescent tool discovery and development, along with applications of the probes in cells, tissues, and organisms. Collectively, these tools are improving in vivo imaging capabilities and bolstering new research directions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bio-sensing with butterfly wings: naturally occurring nano-structures for SERS-based malaria parasite detection.

PubMed

Garrett, Natalie L; Sekine, Ryo; Dixon, Matthew W A; Tilley, Leann; Bambery, Keith R; Wood, Bayden R

2015-09-07

Surface enhanced Raman scattering (SERS) is a powerful tool with great potential to provide improved bio-sensing capabilities. The current 'gold-standard' method for diagnosis of malaria involves visual inspection of blood smears using light microscopy, which is time consuming and can prevent early diagnosis of the disease. We present a novel surface-enhanced Raman spectroscopy substrate based on gold-coated butterfly wings, which enabled detection of malarial hemozoin pigment within lysed blood samples containing 0.005% and 0.0005% infected red blood cells.

Perceptual training yields rapid improvements in visually impaired youth

PubMed Central

Nyquist, Jeffrey B.; Lappin, Joseph S.; Zhang, Ruyuan; Tadin, Duje

2016-01-01

Visual function demands coordinated responses to information over a wide field of view, involving both central and peripheral vision. Visually impaired individuals often seem to underutilize peripheral vision, even in absence of obvious peripheral deficits. Motivated by perceptual training studies with typically sighted adults, we examined the effectiveness of perceptual training in improving peripheral perception of visually impaired youth. Here, we evaluated the effectiveness of three training regimens: (1) an action video game, (2) a psychophysical task that combined attentional tracking with a spatially and temporally unpredictable motion discrimination task, and (3) a control video game. Training with both the action video game and modified attentional tracking yielded improvements in visual performance. Training effects were generally larger in the far periphery and appear to be stable 12 months after training. These results indicate that peripheral perception might be under-utilized by visually impaired youth and that this underutilization can be improved with only ~8 hours of perceptual training. Moreover, the similarity of improvements following attentional tracking and action video-game training suggest that well-documented effects of action video-game training might be due to the sustained deployment of attention to multiple dynamic targets while concurrently requiring rapid attending and perception of unpredictable events. PMID:27901026

Multivariable manual control with simultaneous visual and auditory presentation of information. [for improved compensatory tracking performance of human operator

NASA Technical Reports Server (NTRS)

Uhlemann, H.; Geiser, G.

1975-01-01

Multivariable manual compensatory tracking experiments were carried out in order to determine typical strategies of the human operator and conditions for improvement of his performance if one of the visual displays of the tracking errors is supplemented by an auditory feedback. Because the tracking error of the system which is only visually displayed is found to decrease, but not in general that of the auditorally supported system, it was concluded that the auditory feedback unloads the visual system of the operator who can then concentrate on the remaining exclusively visual displays.

Enhancing Visualization Skills-Improving Options and Success (EnViSIONS) of Engineering and Technology Students

ERIC Educational Resources Information Center

Veurink, N. L.; Hamlin, A. J.; Kampe; J. C. M.; Sorby, S. A.; Blasko, D. G.; Holliday-Darr, K. A.; Kremer, J. D. Trich; Harris, L. V. Abe; Connolly, P. E.; Sadowski, M. A.; Harris, K. S.; Brus, C. P.; Boyle, L. N.; Study, N. E.; Knott, T. W.

2009-01-01

Spatial visualization skills are vital to many careers and in particular to STEM fields. Materials have been developed at Michigan Technological University and Penn State Erie, The Behrend College to assess and develop spatial skills. The EnViSIONS (Enhancing Visualization Skills-Improving Options aNd Success) project is combining these materials…

Visual Design Guidelines for Improving Learning from Dynamic and Interactive Digital Text

ERIC Educational Resources Information Center

Jin, Sung-Hee

2013-01-01

Despite the dynamic and interactive features of digital text, the visual design guidelines for digital text are similar to those for printed text. The purpose of this study was to develop visual design guidelines for improving learning from dynamic and interactive digital text and to validate them by controlled testing. Two structure design…

Visual Working Memory in Deaf Children with Diverse Communication Modes: Improvement by Differential Outcomes

ERIC Educational Resources Information Center

Lopez-Crespo, Ginesa; Daza, Maria Teresa; Mendez-Lopez, Magdalena

2012-01-01

Although visual functions have been proposed to be enhanced in deaf individuals, empirical studies have not yet established clear evidence on this issue. The present study aimed to determine whether deaf children with diverse communication modes had superior visual memory and whether their performance was improved by the use of differential…

Nanowire arrays restore vision in blind mice.

PubMed

Tang, Jing; Qin, Nan; Chong, Yan; Diao, Yupu; Yiliguma; Wang, Zhexuan; Xue, Tian; Jiang, Min; Zhang, Jiayi; Zheng, Gengfeng

2018-03-06

The restoration of light response with complex spatiotemporal features in retinal degenerative diseases towards retinal prosthesis has proven to be a considerable challenge over the past decades. Herein, inspired by the structure and function of photoreceptors in retinas, we develop artificial photoreceptors based on gold nanoparticle-decorated titania nanowire arrays, for restoration of visual responses in the blind mice with degenerated photoreceptors. Green, blue and near UV light responses in the retinal ganglion cells (RGCs) are restored with a spatial resolution better than 100 µm. ON responses in RGCs are blocked by glutamatergic antagonists, suggesting functional preservation of the remaining retinal circuits. Moreover, neurons in the primary visual cortex respond to light after subretinal implant of nanowire arrays. Improvement in pupillary light reflex suggests the behavioral recovery of light sensitivity. Our study will shed light on the development of a new generation of optoelectronic toolkits for subretinal prosthetic devices.

Electron Tomography of Cryo-Immobilized Plant Tissue: A Novel Approach to Studying 3D Macromolecular Architecture of Mature Plant Cell Walls In Situ

PubMed Central

Sarkar, Purbasha; Bosneaga, Elena; Yap, Edgar G.; Das, Jyotirmoy; Tsai, Wen-Ting; Cabal, Angelo; Neuhaus, Erica; Maji, Dolonchampa; Kumar, Shailabh; Joo, Michael; Yakovlev, Sergey; Csencsits, Roseann; Yu, Zeyun; Bajaj, Chandrajit; Downing, Kenneth H.; Auer, Manfred

2014-01-01

Cost-effective production of lignocellulosic biofuel requires efficient breakdown of cell walls present in plant biomass to retrieve the wall polysaccharides for fermentation. In-depth knowledge of plant cell wall composition is therefore essential for improving the fuel production process. The precise spatial three-dimensional (3D) organization of cellulose, hemicellulose, pectin and lignin within plant cell walls remains unclear to date since the microscopy techniques used so far have been limited to two-dimensional, topographic or low-resolution imaging, or required isolation or chemical extraction of the cell walls. In this paper we demonstrate that by cryo-immobilizing fresh tissue, then either cryo-sectioning or freeze-substituting and resin embedding, followed by cryo- or room temperature (RT) electron tomography, respectively, we can visualize previously unseen details of plant cell wall architecture in 3D, at macromolecular resolution (∼2 nm), and in near-native state. Qualitative and quantitative analyses showed that wall organization of cryo-immobilized samples were preserved remarkably better than conventionally prepared samples that suffer substantial extraction. Lignin-less primary cell walls were well preserved in both self-pressurized rapidly frozen (SPRF), cryo-sectioned samples as well as high-pressure frozen, freeze-substituted and resin embedded (HPF-FS-resin) samples. Lignin-rich secondary cell walls appeared featureless in HPF-FS-resin sections presumably due to poor stain penetration, but their macromolecular features could be visualized in unprecedented details in our cryo-sections. While cryo-tomography of vitreous tissue sections is currently proving to be instrumental in developing 3D models of lignin-rich secondary cell walls, here we confirm that the technically easier method of RT-tomography of HPF-FS-resin sections could be used immediately for routine study of low-lignin cell walls. As a proof of principle, we characterized the primary cell walls of a mutant (cob-6) and wild type Arabidopsis hypocotyl parenchyma cells by RT-tomography of HPF-FS-resin sections, and detected a small but significant difference in spatial organization of cellulose microfibrils in the mutant walls. PMID:25207917

Temporal and spatial tuning of dorsal lateral geniculate nucleus neurons in unanesthetized rats

PubMed Central

Sriram, Balaji; Meier, Philip M.

2016-01-01

Visual response properties of neurons in the dorsolateral geniculate nucleus (dLGN) have been well described in several species, but not in rats. Analysis of responses from the unanesthetized rat dLGN will be needed to develop quantitative models that account for visual behavior of rats. We recorded visual responses from 130 single units in the dLGN of 7 unanesthetized rats. We report the response amplitudes, temporal frequency, and spatial frequency sensitivities in this population of cells. In response to 2-Hz visual stimulation, dLGN cells fired 15.9 ± 11.4 spikes/s (mean ± SD) modulated by 10.7 ± 8.4 spikes/s about the mean. The optimal temporal frequency for full-field stimulation ranged from 5.8 to 19.6 Hz across cells. The temporal high-frequency cutoff ranged from 11.7 to 33.6 Hz. Some cells responded best to low temporal frequency stimulation (low pass), and others were strictly bandpass; most cells fell between these extremes. At 2- to 4-Hz temporal modulation, the spatial frequency of drifting grating that drove cells best ranged from 0.008 to 0.18 cycles per degree (cpd) across cells. The high-frequency cutoff ranged from 0.01 to 1.07 cpd across cells. The majority of cells were driven best by the lowest spatial frequency tested, but many were partially or strictly bandpass. We conclude that single units in the rat dLGN can respond vigorously to temporal modulation up to at least 30 Hz and spatial detail up to 1 cpd. Tuning properties were heterogeneous, but each fell along a continuum; we found no obvious clustering into discrete cell types along these dimensions. PMID:26936980

The AMERE project: Enabling real-time detection of radiation effects in individual cells in deep space

NASA Astrophysics Data System (ADS)

De Vos, Winnok H.; Meesen, Geert; Szpirer, Cedric; Scohy, Sophie; Cherukuri, Chaitanya; Evrard, Olivier; Hutsebaut, Xavier; Beghuin, Didier

2012-12-01

A major concern for long-term deep space missions is the detrimental impact of cosmic radiation on human health. Especially the presence of high-energy particles of high atomic mass (HZE) represents a serious threat. To contribute to a fundamental understanding of space radiation effects and to help improving risk assessment for humans on the Moon, the ESA Lunar Lander mission model payload includes a package dedicated to cell-based radiobiology experiments in the form of an Autonomous Microscope for Examination of Radiation Effects (AMERE). The purpose of this setup is to enable real-time visualization of DNA damage repair in living cells after traversal of HZE particles on the Moon. To assess the feasibility of this challenging experiment, we have analysed the biological and technological demands. In this article, we discuss the experimental concept, the biological considerations and describe the implications for system design.

A Fusion Algorithm for GFP Image and Phase Contrast Image of Arabidopsis Cell Based on SFL-Contourlet Transform

PubMed Central

Feng, Peng; Wang, Jing; Wei, Biao; Mi, Deling

2013-01-01

A hybrid multiscale and multilevel image fusion algorithm for green fluorescent protein (GFP) image and phase contrast image of Arabidopsis cell is proposed in this paper. Combining intensity-hue-saturation (IHS) transform and sharp frequency localization Contourlet transform (SFL-CT), this algorithm uses different fusion strategies for different detailed subbands, which include neighborhood consistency measurement (NCM) that can adaptively find balance between color background and gray structure. Also two kinds of neighborhood classes based on empirical model are taken into consideration. Visual information fidelity (VIF) as an objective criterion is introduced to evaluate the fusion image. The experimental results of 117 groups of Arabidopsis cell image from John Innes Center show that the new algorithm cannot only make the details of original images well preserved but also improve the visibility of the fusion image, which shows the superiority of the novel method to traditional ones. PMID:23476716

Cellular Level Brain Imaging in Behaving Mammals: An Engineering Approach

PubMed Central

Hamel, Elizabeth J.O.; Grewe, Benjamin F.; Parker, Jones G.; Schnitzer, Mark J.

2017-01-01

Fluorescence imaging offers expanding capabilities for recording neural dynamics in behaving mammals, including the means to monitor hundreds of cells targeted by genetic type or connectivity, track cells over weeks, densely sample neurons within local microcircuits, study cells too inactive to isolate in extracellular electrical recordings, and visualize activity in dendrites, axons, or dendritic spines. We discuss recent progress and future directions for imaging in behaving mammals from a systems engineering perspective, which seeks holistic consideration of fluorescent indicators, optical instrumentation, and computational analyses. Today, genetically encoded indicators of neural Ca2+ dynamics are widely used, and those of trans-membrane voltage are rapidly improving. Two complementary imaging paradigms involve conventional microscopes for studying head-restrained animals and head-mounted miniature microscopes for imaging in freely behaving animals. Overall, the field has attained sufficient sophistication that increased cooperation between those designing new indicators, light sources, microscopes, and computational analyses would greatly benefit future progress. PMID:25856491

Spontaneous Resolution of Long-Standing Macular Detachment due to Optic Disc Pit with Significant Visual Improvement.

PubMed

Parikakis, Efstratios A; Chatziralli, Irini P; Peponis, Vasileios G; Karagiannis, Dimitrios; Stratos, Aimilianos; Tsiotra, Vasileia A; Mitropoulos, Panagiotis G

2014-01-01

To report a case of spontaneous resolution of a long-standing serous macular detachment associated with an optic disc pit, leading to significant visual improvement. A 63-year-old female presented with a 6-month history of blurred vision and micropsia in her left eye. Her best-corrected visual acuity was 6/24 in the left eye, and fundoscopy revealed serous macular detachment associated with optic disc pit, which was confirmed by optical coherence tomography (OCT). The patient was offered vitrectomy as a treatment alternative, but she preferred to be reviewed conservatively. Three years after initial presentation, neither macular detachment nor subretinal fluid was evident in OCT, while the inner segment/outer segment (IS/OS) junction line was intact. Her visual acuity was improved from 6/24 to 6/12 in her left eye, remaining stable at the 6-month follow-up after resolution. We present a case of spontaneous resolution of a long-standing macular detachment associated with an optic disc pit with significant visual improvement, postulating that the integrity of the IS/OS junction line may be a prognostic factor for final visual acuity and suggesting OCT as an indicator of visual prognosis and the probable necessity of a surgical management.

Effects of deuterium oxide and galvanic vestibular stimulation on visual cortical cell function

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

Reinis, S.; Landolt, J.P.; Weiss, D.S.

1984-03-01

The spontaneous and evoked unit activities of complex visual cortical cells were recorded from Brodmann's area 18 in immobilized, unanesthetized cats before, during, and after stimulation of the vestibular system. The vestibular system was stimulated by intravenous injection of deuterium oxide (D2O)--a noted nystagmogenic agent--or by direct galvanic stimulation of the labyrinth. Measures of the receptive-field areas, poststimulus time histograms, directional preferences, and the optimal speed of the light bar stimulating the cell were obtained before and after the application of D2O. Directional preferences were determined in a novel manner, using a method derived from a hierarchical clustering technique. Datamore » were collected and analyzed from a) visual cortical cells in cats with intact labyrinths, b) visual cortical cells in cats following bilateral labrinthectomies, and c) nonvisual cortical cells in cats with intact labyrinths. The other cellular characteristics were also altered by the D2O. Galvanic stimulation of the labyrinth resembles, in its effects, the injection of D2O. In labyrinth-intact cats, the time course of area 18 spontaneous activity dramatically increased 30 min or more after D2O was administered. It peaked 2-3 h later and still had not returned to preinjection levels even 7 h after the D2O administration. In bilaterally labyrinthectomized cats, the spontaneous activity of the visual cells did not change following D2O administration. In nonvisual cells from labyrinth-intact cats, the spontaneous activity demonstrated a slight but significant decrease over time after D2O injection. In pilot studies, the cats were injected with D2O. Within 8-10 min afterward, signs of positional nystagmus commenced; and within 30 min, problems in maintaining balance were noted. This continued for 7-8 h before disappearing. In the labyrinthectomized animals, such effects were not observed.« less

In situ hybridization analysis of the expression of futsch, tau, and MESK2 homologues in the brain of the European honeybee (Apis mellifera L.).

PubMed

Kaneko, Kumi; Hori, Sayaka; Morimoto, Mai M; Nakaoka, Takayoshi; Paul, Rajib Kumar; Fujiyuki, Tomoko; Shirai, Kenichi; Wakamoto, Akiko; Tsuboko, Satomi; Takeuchi, Hideaki; Kubo, Takeo

2010-02-16

The importance of visual sense in Hymenopteran social behavior is suggested by the existence of a Hymenopteran insect-specific neural circuit related to visual processing and the fact that worker honeybee brain changes morphologically according to its foraging experience. To analyze molecular and neural bases that underlie the visual abilities of the honeybees, we used a cDNA microarray to search for gene(s) expressed in a neural cell-type preferential manner in a visual center of the honeybee brain, the optic lobes (OLs). Expression analysis of candidate genes using in situ hybridization revealed two genes expressed in a neural cell-type preferential manner in the OLs. One is a homologue of Drosophila futsch, which encodes a microtubule-associated protein and is preferentially expressed in the monopolar cells in the lamina of the OLs. The gene for another microtubule-associated protein, tau, which functionally overlaps with futsch, was also preferentially expressed in the monopolar cells, strongly suggesting the functional importance of these two microtubule-associated proteins in monopolar cells. The other gene encoded a homologue of Misexpression Suppressor of Dominant-negative Kinase Suppressor of Ras 2 (MESK2), which might activate Ras/MAPK-signaling in Drosophila. MESK2 was expressed preferentially in a subclass of neurons located in the ventral region between the lamina and medulla neuropil in the OLs, suggesting that this subclass is a novel OL neuron type characterized by MESK2-expression. These three genes exhibited similar expression patterns in the worker, drone, and queen brains, suggesting that they function similarly irrespective of the honeybee sex or caste. Here we identified genes that are expressed in a monopolar cell (Amfutsch and Amtau) or ventral medulla-preferential manner (AmMESK2) in insect OLs. These genes may aid in visualizing neurites of monopolar cells and ventral medulla cells, as well as in analyzing the function of these neurons.

Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on spatial response properties of relay cells

PubMed Central

Martínez-Cañada, Pablo; Halnes, Geir; Fyhn, Marianne

2018-01-01

Despite half-a-century of research since the seminal work of Hubel and Wiesel, the role of the dorsal lateral geniculate nucleus (dLGN) in shaping the visual signals is not properly understood. Placed on route from retina to primary visual cortex in the early visual pathway, a striking feature of the dLGN circuit is that both the relay cells (RCs) and interneurons (INs) not only receive feedforward input from retinal ganglion cells, but also a prominent feedback from cells in layer 6 of visual cortex. This feedback has been proposed to affect synchronicity and other temporal properties of the RC firing. It has also been seen to affect spatial properties such as the center-surround antagonism of thalamic receptive fields, i.e., the suppression of the response to very large stimuli compared to smaller, more optimal stimuli. Here we explore the spatial effects of cortical feedback on the RC response by means of a a comprehensive network model with biophysically detailed, single-compartment and multicompartment neuron models of RCs, INs and a population of orientation-selective layer 6 simple cells, consisting of pyramidal cells (PY). We have considered two different arrangements of synaptic feedback from the ON and OFF zones in the visual cortex to the dLGN: phase-reversed (‘push-pull’) and phase-matched (‘push-push’), as well as different spatial extents of the corticothalamic projection pattern. Our simulation results support that a phase-reversed arrangement provides a more effective way for cortical feedback to provide the increased center-surround antagonism seen in experiments both for flashing spots and, even more prominently, for patch gratings. This implies that ON-center RCs receive direct excitation from OFF-dominated cortical cells and indirect inhibitory feedback from ON-dominated cortical cells. The increased center-surround antagonism in the model is accompanied by spatial focusing, i.e., the maximum RC response occurs for smaller stimuli when feedback is present. PMID:29377888

Noninvasive near infrared autofluorescence imaging of retinal pigment epithelial cells in the human retina using adaptive optics.

PubMed

Liu, Tao; Jung, HaeWon; Liu, Jianfei; Droettboom, Michael; Tam, Johnny

2017-10-01

The retinal pigment epithelial (RPE) cells contain intrinsic fluorophores that can be visualized using infrared autofluorescence (IRAF). Although IRAF is routinely utilized in the clinic for visualizing retinal health and disease, currently, it is not possible to discern cellular details using IRAF due to limits in resolution. We demonstrate that the combination of adaptive optics (AO) with IRAF (AO-IRAF) enables higher-resolution imaging of the IRAF signal, revealing the RPE mosaic in the living human eye. Quantitative analysis of visualized RPE cells in 10 healthy subjects across various eccentricities demonstrates the possibility for in vivo density measurements of RPE cells, which range from 6505 to 5388 cells/mm 2 for the areas measured (peaking at the fovea). We also identified cone photoreceptors in relation to underlying RPE cells, and found that RPE cells support on average up to 18.74 cone photoreceptors in the fovea down to an average of 1.03 cone photoreceptors per RPE cell at an eccentricity of 6 mm. Clinical application of AO-IRAF to a patient with retinitis pigmentosa illustrates the potential for AO-IRAF imaging to become a valuable complementary approach to the current landscape of high resolution imaging modalities.

Latent fingermark development on a range of porous substrates using ninhydrin analogs--a comparison with ninhydrin and 1,8-diazofluoren.

PubMed

Berdejo, Stephanie; Rowe, Mark; Bond, John W

2012-03-01

Three relatively new reagents for developing latent fingermarks on porous substrates, 1,2-indandione (IND), 5-methylthioninhydrin (5-MTN), and lawsone, are compared with the more widely used ninhydrin and 1,8-diazofluoren (DFO). Developed latent fingermark visualization on 10 different substrates comprising colored papers, cardboard, and cellophane rather than conventional printer and writing/notepad paper is assessed using latent fingermark deposits from 48 donors. Results show improved fluorescent fingermark visualization using IND compared with DFO on a range of colored cardboards and thick white paper, thus extending the range of substrates known to yield improved visualization with IND. Adding zinc chloride to IND failed to yield any further improvement in fluorescent fingermark visualization. 5-MTN (with and without zinc chloride posttreatment) showed no improvement in visualization compared with ninhydrin and DFO although visible fingermarks were developed. Lawsone produced fluorescent visible fingermarks only with white substrates, which were inferior to those produced with DFO. © 2011 American Academy of Forensic Sciences.

Perceptual learning increases the strength of the earliest signals in visual cortex.

PubMed

Bao, Min; Yang, Lin; Rios, Cristina; He, Bin; Engel, Stephen A

2010-11-10

Training improves performance on most visual tasks. Such perceptual learning can modify how information is read out from, and represented in, later visual areas, but effects on early visual cortex are controversial. In particular, it remains unknown whether learning can reshape neural response properties in early visual areas independent from feedback arising in later cortical areas. Here, we tested whether learning can modify feedforward signals in early visual cortex as measured by the human electroencephalogram. Fourteen subjects were trained for >24 d to detect a diagonal grating pattern in one quadrant of the visual field. Training improved performance, reducing the contrast needed for reliable detection, and also reliably increased the amplitude of the earliest component of the visual evoked potential, the C1. Control orientations and locations showed smaller effects of training. Because the C1 arises rapidly and has a source in early visual cortex, our results suggest that learning can increase early visual area response through local receptive field changes without feedback from later areas.

The use of computer imaging techniques to visualize cardiac muscle cells in three dimensions.

PubMed

Marino, T A; Cook, P N; Cook, L T; Dwyer, S J

1980-11-01

Atrial muscle cells and atrioventricular bundle cells were reconstructed using a computer-assisted three-dimensional reconstruction system. This reconstruction technique permitted these cells to be viewed from any direction. The cell surfaces were approximated using triangular tiles, and this optimization technique for cell reconstruction allowed for the computation of cell surface area and cell volume. A transparent mode is described which enables the investigator to examine internal cellular features such as the shape and location of the nucleus. In addition, more than one cell can be displayed simultaneously, and, therefore, spatial relationships are preserved and intercellular relationships viewed directly. The use of computer imaging techniques allows for a more complete collection of quantitative morphological data and also the visualization of the morphological information gathered.

Evolution of eye size and shape in primates.

PubMed

Ross, Callum F; Kirk, E Christopher

2007-03-01

Strepsirrhine and haplorhine primates exhibit highly derived features of the visual system that distinguish them from most other mammals. Comparative data link the evolution of these visual specializations to the sequential acquisition of nocturnal visual predation in the primate stem lineage and diurnal visual predation in the anthropoid stem lineage. However, it is unclear to what extent these shifts in primate visual ecology were accompanied by changes in eye size and shape. Here we investigate the evolution of primate eye morphology using a comparative study of a large sample of mammalian eyes. Our analysis shows that primates differ from other mammals in having large eyes relative to body size and that anthropoids exhibit unusually small corneas relative to eye size and body size. The large eyes of basal primates probably evolved to improve visual acuity while maintaining high sensitivity in a nocturnal context. The reduced corneal sizes of anthropoids reflect reductions in the size of the dioptric apparatus as a means of increasing posterior nodal distance to improve visual acuity. These data support the conclusion that the origin of anthropoids was associated with a change in eye shape to improve visual acuity in the context of a diurnal predatory habitus.

High-Resolution Intravital Microscopy

PubMed Central

Andresen, Volker; Pollok, Karolin; Rinnenthal, Jan-Leo; Oehme, Laura; Günther, Robert; Spiecker, Heinrich; Radbruch, Helena; Gerhard, Jenny; Sporbert, Anje; Cseresnyes, Zoltan; Hauser, Anja E.; Niesner, Raluca

2012-01-01

Cellular communication constitutes a fundamental mechanism of life, for instance by permitting transfer of information through synapses in the nervous system and by leading to activation of cells during the course of immune responses. Monitoring cell-cell interactions within living adult organisms is crucial in order to draw conclusions on their behavior with respect to the fate of cells, tissues and organs. Until now, there is no technology available that enables dynamic imaging deep within the tissue of living adult organisms at sub-cellular resolution, i.e. detection at the level of few protein molecules. Here we present a novel approach called multi-beam striped-illumination which applies for the first time the principle and advantages of structured-illumination, spatial modulation of the excitation pattern, to laser-scanning-microscopy. We use this approach in two-photon-microscopy - the most adequate optical deep-tissue imaging-technique. As compared to standard two-photon-microscopy, it achieves significant contrast enhancement and up to 3-fold improved axial resolution (optical sectioning) while photobleaching, photodamage and acquisition speed are similar. Its imaging depth is comparable to multifocal two-photon-microscopy and only slightly less than in standard single-beam two-photon-microscopy. Precisely, our studies within mouse lymph nodes demonstrated 216% improved axial and 23% improved lateral resolutions at a depth of 80 µm below the surface. Thus, we are for the first time able to visualize the dynamic interactions between B cells and immune complex deposits on follicular dendritic cells within germinal centers (GCs) of live mice. These interactions play a decisive role in the process of clonal selection, leading to affinity maturation of the humoral immune response. This novel high-resolution intravital microscopy method has a huge potential for numerous applications in neurosciences, immunology, cancer research and developmental biology. Moreover, our striped-illumination approach is able to improve the resolution of any laser-scanning-microscope, including confocal microscopes, by simply choosing an appropriate detector. PMID:23251402

Genomic localization of the Z/EG transgene in the mouse genome.

PubMed

Colombo, Sophie; Kumasaka, Mayuko; Lobe, Corrinne; Larue, Lionel

2010-02-01

The Z/EG transgenic mouse line, produced by Novak et al., displays tissue-specific EGFP expression after Cre-mediated recombination. The autofluorescence of EGFP allows the visualization of cells of interest displaying Cre recombination. The initial construct was designed such that cells without Cre recombination express the beta-galactosidase marker, facilitating counterselection. We used inverse PCR to identify the site of integration of the Z/EG transgene, to improve the efficiency of homozygous Z/EG mouse production. Recombined cells produced large amounts of EGFP protein, resulting in higher levels of fluorescence and therefore greater contrast with nonrecombined cells. We mapped the transgene to the G1 region of chromosome 5. This random insertion was found to have occurred 230-bp upstream from the start codon of the Rasa4 gene. The insertion of the Z/EG transgene in the C57BL/6 genetic background had no effect on Rasa4 expression. Homozygous Z/EG mice therefore had no obvious phenotype. (c) 2009 Wiley-Liss, Inc.

Genetically Encoded Molecular Tension Probe for Tracing Protein-Protein Interactions in Mammalian Cells.

PubMed

Kim, Sung Bae; Nishihara, Ryo; Citterio, Daniel; Suzuki, Koji

2016-02-17

Optical imaging of protein-protein interactions (PPIs) facilitates comprehensive elucidation of intracellular molecular events. We demonstrate an optical measure for visualizing molecular tension triggered by any PPI in mammalian cells. Twenty-three kinds of candidate designs were fabricated, in which a full-length artificial luciferase (ALuc) was sandwiched between two model proteins of interest, e.g., FKBP and FRB. One of the designs greatly enhanced the bioluminescence in response to varying concentrations of rapamycin. It is confirmed with negative controls that the elevated bioluminescence is solely motivated from the molecular tension. The probe design was further modified toward eliminating the C-terminal end of ALuc and was found to improve signal-to-background ratios, named "a combinational probe". The utilities were elucidated with detailed substrate selectivity, bioluminescence imaging of live cells, and different PPI models. This study expands capabilities of luciferases as a tool for analyses of molecular dynamics and cell signaling in living subjects.

Müller cells separate between wavelengths to improve day vision with minimal effect upon night vision

NASA Astrophysics Data System (ADS)

Labin, Amichai M.; Safuri, Shadi K.; Ribak, Erez N.; Perlman, Ido

2014-07-01

Vision starts with the absorption of light by the retinal photoreceptors—cones and rods. However, due to the ‘inverted’ structure of the retina, the incident light must propagate through reflecting and scattering cellular layers before reaching the photoreceptors. It has been recently suggested that Müller cells function as optical fibres in the retina, transferring light illuminating the retinal surface onto the cone photoreceptors. Here we show that Müller cells are wavelength-dependent wave-guides, concentrating the green-red part of the visible spectrum onto cones and allowing the blue-purple part to leak onto nearby rods. This phenomenon is observed in the isolated retina and explained by a computational model, for the guinea pig and the human parafoveal retina. Therefore, light propagation by Müller cells through the retina can be considered as an integral part of the first step in the visual process, increasing photon absorption by cones while minimally affecting rod-mediated vision.

DrImpute: imputing dropout events in single cell RNA sequencing data.

PubMed

Gong, Wuming; Kwak, Il-Youp; Pota, Pruthvi; Koyano-Nakagawa, Naoko; Garry, Daniel J

2018-06-08

The single cell RNA sequencing (scRNA-seq) technique begin a new era by allowing the observation of gene expression at the single cell level. However, there is also a large amount of technical and biological noise. Because of the low number of RNA transcriptomes and the stochastic nature of the gene expression pattern, there is a high chance of missing nonzero entries as zero, which are called dropout events. We develop DrImpute to impute dropout events in scRNA-seq data. We show that DrImpute has significantly better performance on the separation of the dropout zeros from true zeros than existing imputation algorithms. We also demonstrate that DrImpute can significantly improve the performance of existing tools for clustering, visualization and lineage reconstruction of nine published scRNA-seq datasets. DrImpute can serve as a very useful addition to the currently existing statistical tools for single cell RNA-seq analysis. DrImpute is implemented in R and is available at https://github.com/gongx030/DrImpute .

Modeling the impact of common noise inputs on the network activity of retinal ganglion cells

PubMed Central

Ahmadian, Yashar; Shlens, Jonathon; Pillow, Jonathan W.; Kulkarni, Jayant; Litke, Alan M.; Chichilnisky, E. J.; Simoncelli, Eero; Paninski, Liam

2013-01-01

Synchronized spontaneous firing among retinal ganglion cells (RGCs), on timescales faster than visual responses, has been reported in many studies. Two candidate mechanisms of synchronized firing include direct coupling and shared noisy inputs. In neighboring parasol cells of primate retina, which exhibit rapid synchronized firing that has been studied extensively, recent experimental work indicates that direct electrical or synaptic coupling is weak, but shared synaptic input in the absence of modulated stimuli is strong. However, previous modeling efforts have not accounted for this aspect of firing in the parasol cell population. Here we develop a new model that incorporates the effects of common noise, and apply it to analyze the light responses and synchronized firing of a large, densely-sampled network of over 250 simultaneously recorded parasol cells. We use a generalized linear model in which the spike rate in each cell is determined by the linear combination of the spatio-temporally filtered visual input, the temporally filtered prior spikes of that cell, and unobserved sources representing common noise. The model accurately captures the statistical structure of the spike trains and the encoding of the visual stimulus, without the direct coupling assumption present in previous modeling work. Finally, we examined the problem of decoding the visual stimulus from the spike train given the estimated parameters. The common-noise model produces Bayesian decoding performance as accurate as that of a model with direct coupling, but with significantly more robustness to spike timing perturbations. PMID:22203465

Image analysis in cytology: DNA-histogramming versus cervical smear prescreening.

PubMed

Bengtsson, E W; Nordin, B

1993-01-01

The visual inspection of cellular specimens and histological sections through a light microscope plays an important role in clinical medicine and biomedical research. The human visual system is very good at the recognition of various patterns but less efficient at quantitative assessment of these patterns. Some samples are prepared in great numbers, most notably the screening for cervical cancer, the so-called PAP-smears, which results in hundreds of millions of samples each year, creating a tedious mass inspection task. Numerous attempts have been made over the last 40 years to create systems that solve these two tasks, the quantitative supplement to the human visual system and the automation of mass screening. The most difficult task, the total automation, has received the greatest attention with many large scale projects over the decades. In spite of all these efforts, still no generally accepted automated prescreening device exists on the market. The main reason for this failure is the great pattern recognition capabilities needed to distinguish between cancer cells and all other kinds of objects found in the specimens: cellular clusters, debris, degenerate cells, etc. Improved algorithms, the ever-increasing processing power of computers and progress in biochemical specimen preparation techniques make it likely that eventually useful automated prescreening systems will become available. Meanwhile, much less effort has been put into the development of interactive cell image analysis systems. Still, some such systems have been developed and put into use at thousands of laboratories worldwide. In these the human pattern recognition capability is used to select the fields and objects that are to be analysed while the computational power of the computer is used for the quantitative analysis of cellular DNA content or other relevant markers. Numerous studies have shown that the quantitative information about the distribution of cellular DNA content is of prognostic significance in many types of cancer. Several laboratories are therefore putting these techniques into routine clinical use. The more advanced systems can also study many other markers and cellular features, some known to be of clinical interest, others useful in research. The advances in computer technology are making these systems more generally available through decreasing cost, increasing computational power and improved user interfaces. We have been involved in research and development of both automated and interactive cell analysis systems during the last 20 years. Here some experiences and conclusions from this work will be presented as well as some predictions about what can be expected in the near future.

Effect of Chromoendoscopy Filters on Visualization of KTP Laser-Associated Tissue Changes: A Cadaveric Animal Model.

PubMed

Johnson, Christopher M; Pate, Mariah B; Postma, Gregory N

2018-04-01

Standard KTP laser (potassium titanyl phosphate) wavelength-specific protective eyewear often impairs visualization of tissue changes during laser treatment. This sometimes necessitates eyewear removal to evaluate tissue effects, which wastes time and poses safety concerns. The objective was to determine if "virtual" or "electronic" chromoendoscopy filters, as found on some endoscopy platforms, could alleviate the restricted visualization inherent to protective eyewear. A KTP laser was applied to porcine laryngeal tissue and recorded via video laryngoscopy with 1 optical (Olympus Narrow Band Imaging) and 8 digital (Pentax Medical I-scan) chromoendoscopy filters. Videos were viewed by 11 otolaryngologists wearing protective eyewear. Using a discrete visual analog scale, they rated each filter on its ability to improve visualization,. No filter impaired visualization; 5 of 9 improved visualization. Based on statistical significance, the number of positive responses, and the lack of negative responses, narrow band imaging and the I-scan tone enhancement filter for leukoplakia performed best. These filters could shorten procedure time and improve safety; therefore, further clinical evaluation is warranted.

Effects of L-arginine on anatomical and electrophysiological deterioration of the eye in a rodent model of nonarteritic ischemic optic neuropathy.

PubMed

Chuman, Hideki; Maekubo, Tomoyuki; Osako, Takako; Ishiai, Michitaka; Kawano, Naoko; Nao-I, Nobuhisa

2013-07-01

The aims of this study were to clarify the effectiveness of L-arginine (1) for reducing the severity of anatomical changes in the eye and improving visual function in the acute stage of a rodent model of nonarteritic ischemic optic neuropathy (rNAION) and (2) in preventing those changes in anatomy and visual function. For the first aim, L-arginine was intravenously injected into rats 3 h after rNAION induction; for the second aim, rNAION was induced after the oral administration of L-arginine for 7 days. The inner retinal thickness was determined over time by optical coherence tomography, and the amplitude of the scotopic threshold response (STR) and the number of surviving retinal ganglion cells (RGCs) were measured. These data were compared with the baseline data from the control group. Both intravenous infusion of L-arginine after rNAION induction and oral pretreatment with L-arginine significantly decreased optic disc edema in the acute stage and thinning of the inner retina, reduced the decrease in STR amplitude, and reduced the decrease in the number of RGCs during rNAION. Based on these results, we conclude that L-arginine treatment is effective for reducing anatomical changes in the eye and improving visual function in the acute stage of rNAION and that pretreatment with L-arginine is an effective therapy to reduce the severity of the condition during recurrence in the other eye.

A ratiometric fluorescent molecular probe for visualization of mitochondrial temperature in living cells.

PubMed

Homma, Mitsumasa; Takei, Yoshiaki; Murata, Atsushi; Inoue, Takafumi; Takeoka, Shinji

2015-04-11

Mitochondrial thermodynamics is the key to understand cellular activities related to homeostasis and energy balance. Here, we report the first ratiometric fluorescent molecular probe (Mito-RTP) that is selectively localized in the mitochondria and visualize the temperature. We confirmed that Mito-RTP could work as a ratiometric thermometer in a cuvette and living cells.

Glial cell migration in the eye disc.

PubMed

Silies, Marion; Yuva, Yeliz; Engelen, Daniel; Aho, Annukka; Stork, Tobias; Klämbt, Christian

2007-11-28

Any complex nervous system is made out of two major cell types, neurons and glial cells. A hallmark of glial cells is their pronounced ability to migrate. En route to their final destinations, glial cells are generally guided by neuronal signals. Here we show that in the developing visual system of Drosophila glial cell migration is largely controlled by glial-glial interactions and occurs independently of axonal contact. Differentiation into wrapping glia is initiated close to the morphogenetic furrow. Using single cell labeling experiments we identified six distinct glial cell types in the eye disc. The migratory glial population is separated from the wrapping glial cells by the so-called carpet cells, extraordinary large glial cells, each covering a surface area of approximately 10,000 epithelial cells. Subsequent cell ablation experiments demonstrate that the carpet glia regulates glial migration in the eye disc epithelium and suggest a new model underlying glial migration and differentiation in the developing visual system.

Cytomegalovirus retinitis and HIV: Case reviews from KwaZulu-Natal Province, South Africa.

PubMed

Hassan-Moosa, R; Chinappa, T; Jeena, L; Visser, L; Naidoo, K

2017-09-22

Retinal cytomegalovirus (CMV) infection is a common opportunistic infection and remains a significant contributor to visual loss in patients with AIDS. We highlight the poor outcomes of CMV retinitis in three HIV-infected patients who were initiated on antiretroviral therapy (ART). We conducted a retrospective chart review of advanced stage HIV-infected patients with known CMV retinitis.Case 1. A 37-year-old man, with a CD4+ cell count of 35 cells/µL, presented for ART initiation with a 5-month history of visual loss in his left eye. Fundoscopy showed left eye CMV retinitis and right eye HIV retinopathy. ART and 5 months of weekly intravitreal ganciclovir injections (left eye) were commenced. Six-month outcomes included virological suppression, and visual acuity in the right eye of 6/6 and in the left eye of 3/60.Case 2. A 31-year-old woman, with a CD4+ cell count of 39 cells/µL and on tuberculosis therapy, presented for ART initiation. She presented with a 2-month history of decreased visual acuity. Fundoscopy showed bilateral CMV retinitis, which was more pronounced in the left eye. ART and 8 months of intravitreal ganciclovir injections were commenced. Six-month outcomes included virological suppression and visual acuity in the right eye of 6/9, and in the left eye of 6/24.Case 3. A 29-year-old woman, with a CD4+ cell count of 24 cells/µL, who was on tuberculosis therapy and ART, complained of blurred vision at her 2-month ART follow-up visit. Fundoscopy showed bilateral retinal detachment secondary to CMV retinitis. While silicone oil tamponade and subsequent retinectomy successfully repaired the right eye, extensive damage rendered the left eye irreparable. Six-month outcomes included virological suppression, with 6/120 visual acuity in the right eye and complete blindness in the left eye. CMV retinitis causes debilitating, permanent sequelae, which is preventable by ART initiation at higher CD4+ cell counts. Despite achieving virological suppression, vision could not be completely restored in these patients, irrespective of the severity of CMV retinitis.

Impact of low vision rehabilitation on functional vision performance of children with visual impairment.

PubMed

Ganesh, Suma; Sethi, Sumita; Srivastav, Sonia; Chaudhary, Amrita; Arora, Priyanka

2013-09-01

To evaluate the impact of low vision rehabilitation on functional vision of children with visual impairment. The LV Prasad-Functional Vision Questionnaire, designed specifically to measure functional performance of visually impaired children of developing countries, was used to assess the level of difficulty in performing various tasks pre and post visual rehabilitation in children with documented visual impairment. Chi-square test was used to assess the impact of rehabilitation intervention on functional vision performance; a P < 0.05 was considered significant. LogMAR visual acuity prior to the introduction of low vision devices (LVDs) was 0.90 ± 0.05 for distance and for near it was 0.61 ± 0.05. After the intervention, the acuities improved significantly for distance (0.2 ± 0.27; P < 0.0001) and near (0.42 ± 0.17; P = 0.001). The most common reported difficulties were related to their academic activities like copying from the blackboard (80%), reading textbook at arm's length (77.2%), and writing along a straight line (77.2%). Absolute raw score of disability pre-LVD was 15.05 which improved to 7.58 post-LVD. An improvement in functional vision post visual rehabilitation was especially found in those activities related to their studying lifestyle like copying from the blackboard (P < 0.0001), reading textbook at arm's length (P < 0.0001), and writing along a straight line (P = 0.003). In our study group, there was a significant improvement in functional vision post visual rehabilitation, especially with those activities which are related to their academic output. It is important for these children to have an early visual rehabilitation to decrease the impairment associated with these decreased visual output and to enhance their learning abilities.

Reading Performance Is Enhanced by Visual Texture Discrimination Training in Chinese-Speaking Children with Developmental Dyslexia

PubMed Central

Meng, Xiangzhi; Lin, Ou; Wang, Fang; Jiang, Yuzheng; Song, Yan

2014-01-01

Background High order cognitive processing and learning, such as reading, interact with lower-level sensory processing and learning. Previous studies have reported that visual perceptual training enlarges visual span and, consequently, improves reading speed in young and old people with amblyopia. Recently, a visual perceptual training study in Chinese-speaking children with dyslexia found that the visual texture discrimination thresholds of these children in visual perceptual training significantly correlated with their performance in Chinese character recognition, suggesting that deficits in visual perceptual processing/learning might partly underpin the difficulty in reading Chinese. Methodology/Principal Findings To further clarify whether visual perceptual training improves the measures of reading performance, eighteen children with dyslexia and eighteen typically developed readers that were age- and IQ-matched completed a series of reading measures before and after visual texture discrimination task (TDT) training. Prior to the TDT training, each group of children was split into two equivalent training and non-training groups in terms of all reading measures, IQ, and TDT. The results revealed that the discrimination threshold SOAs of TDT were significantly higher for the children with dyslexia than for the control children before training. Interestingly, training significantly decreased the discrimination threshold SOAs of TDT for both the typically developed readers and the children with dyslexia. More importantly, the training group with dyslexia exhibited significant enhancement in reading fluency, while the non-training group with dyslexia did not show this improvement. Additional follow-up tests showed that the improvement in reading fluency is a long-lasting effect and could be maintained for up to two months in the training group with dyslexia. Conclusion/Significance These results suggest that basic visual perceptual processing/learning and reading ability in Chinese might at least partially rely on overlapping mechanisms. PMID:25247602

Are V1 Simple Cells Optimized for Visual Occlusions? A Comparative Study

PubMed Central

Bornschein, Jörg; Henniges, Marc; Lücke, Jörg

2013-01-01

Simple cells in primary visual cortex were famously found to respond to low-level image components such as edges. Sparse coding and independent component analysis (ICA) emerged as the standard computational models for simple cell coding because they linked their receptive fields to the statistics of visual stimuli. However, a salient feature of image statistics, occlusions of image components, is not considered by these models. Here we ask if occlusions have an effect on the predicted shapes of simple cell receptive fields. We use a comparative approach to answer this question and investigate two models for simple cells: a standard linear model and an occlusive model. For both models we simultaneously estimate optimal receptive fields, sparsity and stimulus noise. The two models are identical except for their component superposition assumption. We find the image encoding and receptive fields predicted by the models to differ significantly. While both models predict many Gabor-like fields, the occlusive model predicts a much sparser encoding and high percentages of ‘globular’ receptive fields. This relatively new center-surround type of simple cell response is observed since reverse correlation is used in experimental studies. While high percentages of ‘globular’ fields can be obtained using specific choices of sparsity and overcompleteness in linear sparse coding, no or only low proportions are reported in the vast majority of studies on linear models (including all ICA models). Likewise, for the here investigated linear model and optimal sparsity, only low proportions of ‘globular’ fields are observed. In comparison, the occlusive model robustly infers high proportions and can match the experimentally observed high proportions of ‘globular’ fields well. Our computational study, therefore, suggests that ‘globular’ fields may be evidence for an optimal encoding of visual occlusions in primary visual cortex. PMID:23754938

The Emergence of Contrast-Invariant Orientation Tuning in Simple Cells of Cat Visual Cortex

PubMed Central

Finn, Ian M.; Priebe, Nicholas J.; Ferster, David

2007-01-01

Simple cells in primary visual cortex exhibit contrast-invariant orientation tuning, in seeming contradiction to feed-forward models relying on lateral geniculate nucleus (LGN) input alone. Contrast invariance has therefore been thought to depend on the presence of intracortical lateral inhibition. In vivo intracellular recordings instead suggest that contrast invariance can be explained by three properties of the excitatory pathway. 1) Depolarizations evoked by orthogonal stimuli are determined by the amount of excitation a cell receives from the LGN, relative to the excitation it receives from other cortical cells. 2) Depolarizations evoked by preferred stimuli saturate at lower contrasts than the spike output of LGN relay cells. 3) Visual stimuli evoke contrast-dependent changes in trial-to-trial variability, which lead to contrast-dependent changes in the relationship between membrane potential and spike rate. Thus, high-contrast, orthogonally-oriented stimuli that evoke significant depolarizations evoke few spikes. Together these mechanisms, without lateral inhibition, can account for contrast-invariant stimulus selectivity. PMID:17408583

Brain State Effects on Layer 4 of the Awake Visual Cortex

PubMed Central

Zhuang, Jun; Bereshpolova, Yulia; Stoelzel, Carl R.; Huff, Joseph M.; Hei, Xiaojuan; Alonso, Jose-Manuel

2014-01-01

Awake mammals can switch between alert and nonalert brain states hundreds of times per day. Here, we study the effects of alertness on two cell classes in layer 4 of primary visual cortex of awake rabbits: presumptive excitatory “simple” cells and presumptive fast-spike inhibitory neurons (suspected inhibitory interneurons). We show that in both cell classes, alertness increases the strength and greatly enhances the reliability of visual responses. In simple cells, alertness also increases the temporal frequency bandwidth, but preserves contrast sensitivity, orientation tuning, and selectivity for direction and spatial frequency. Finally, alertness selectively suppresses the simple cell responses to high-contrast stimuli and stimuli moving orthogonal to the preferred direction, effectively enhancing mid-contrast borders. Using a population coding model, we show that these effects of alertness in simple cells—enhanced reliability, higher gain, and increased suppression in orthogonal orientation—could play a major role at increasing the speed of cortical feature detection. PMID:24623767

Neural mechanism for sensing fast motion in dim light.

PubMed

Li, Ran; Wang, Yi

2013-11-07

Luminance is a fundamental property of visual scenes. A population of neurons in primary visual cortex (V1) is sensitive to uniform luminance. In natural vision, however, the retinal image often changes rapidly. Consequently the luminance signals visual cells receive are transiently varying. How V1 neurons respond to such luminance changes is unknown. By applying large static uniform stimuli or grating stimuli altering at 25 Hz that resemble the rapid luminance changes in the environment, we show that approximately 40% V1 cells responded to rapid luminance changes of uniform stimuli. Most of them strongly preferred luminance decrements. Importantly, when tested with drifting gratings, the preferred speeds of these cells were significantly higher than cells responsive to static grating stimuli but not to uniform stimuli. This responsiveness can be accounted for by the preferences for low spatial frequencies and high temporal frequencies. These luminance-sensitive cells subserve the detection of fast motion under the conditions of dim illumination.