Upregulation of the endothelin A (ETA) receptor and its association with neurodegeneration in a rodent model of glaucoma.

PubMed

McGrady, Nolan R; Minton, Alena Z; Stankowska, Dorota L; He, Shaoqing; Jefferies, Hayden B; Krishnamoorthy, Raghu R

2017-03-01

Primary open angle glaucoma is a heterogeneous group of optic neuropathies that results in optic nerve degeneration and a loss of retinal ganglion cells (RGCs) ultimately causing blindness if allowed to progress. Elevation of intraocular pressure (IOP) is the most attributable risk factor for developing glaucoma and lowering of IOP is currently the only available therapy. However, despite lowering IOP, neurodegenerative effects persist in some patients. Hence, it would be beneficial to develop approaches to promote neuroprotection of RGCs in addition to IOP lowering therapies. The endothelin system is a key target for intervention against glaucomatous neurodegeneration. The endothelin family of peptides and receptors, particularly endothelin-1 (ET-1) and endothelin B (ET B ) receptor, has been shown to have neurodegenerative roles in glaucoma. The purpose of this study was to examine changes in endothelin A (ET A ) receptor protein expression in the retinas of adult male Brown Norway rats following IOP elevation by the Morrison's model of ocular hypertension and the impact of ET A receptor overexpression on RGC viability in vitro. IOP elevation was carried out in one eye of Brown Norway rats by injection of hypertonic saline through episcleral veins. After 2 weeks of IOP elevation, immunohistochemical analysis of retinal sections from rat eyes showed an increasing trend in immunostaining for ET A receptors in multiple retinal layers including the inner plexiform layer, ganglion cell layer and outer plexiform layer. Following 4 weeks of IOP elevation, a significant increase in immunostaining for ET A receptor expression was found in the retina, primarily in the inner plexiform layer and ganglion cells. A modest increase in staining for ET A receptors was also found in the outer plexiform layer in the retina of rats with IOP elevation. Cell culture studies showed that overexpression of ET A receptors in 661W cells as well as primary RGCs decreases cell viability, compared to empty vector transfected cells. Adeno-associated virus mediated overexpression of the ET A receptor produced an increase in the ET B receptor in primary RGCs. Elevated IOP results in an appreciable change in ET A receptor expression in the retina. Overexpression of the ET A receptor results in an overall decrease in cell viability, accompanied by an increase in ET B receptor levels, suggesting the involvement of both ET A and ET B receptors in mediating cell death. These findings raise possibilities for the development of ET A /ET B dual receptor antagonists as neuroprotective treatments for glaucomatous neuropathy.

Acetylcholine receptors in the human retina

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

Hutchins, J.B.; Hollyfield, J.G.

1985-11-01

Evidence for a population of acetylcholine (ACh) receptors in the human retina is presented. The authors have used the irreversible ligand TH-propylbenzilylcholine mustard (TH-PrBCM) to label muscarinic receptors. TH- or SVI-alpha-bungarotoxin (alpha-BTx) was used to label putative nicotinic receptors. Muscarinic receptors are apparently present in the inner plexiform layer of the retina. Autoradiographic grain densities are reduced in the presence of saturating concentrations of atropine, quinuclidinyl benzilate or scopolamine; this indicates that TH-PrBCM binding is specific for a population of muscarinic receptors in the human retina. Binding sites for radiolabeled alpha-BTx are found predominantly in the inner plexiform layer ofmore » the retina. Grain densities are reduced in the presence of d-tubocurarine, indicating that alpha-BTx may bind to a pharmacologically relevant nicotinic ACh receptor. This study provides evidence for cholinergic neurotransmission in the human retina.« less

Serosurvey for the Prevalence of Brucella Canis Antibodies in Dogs in Central Ohio

DTIC Science & Technology

1983-01-01

negative urease production ...................... positive indol production ....................... negative1 0 ,58 ,6 2 citrate utilization...retained its spermatogenic ability. The epididymides had ac- cumulations of lymphocytes in the interstitial cell layers ranging from a few cells to large...There was diffuse in- filtration of plasma cells between the inner plexiform layer and the nerve fiber layer of the retina. Some serous exudate and a few

Alterations in Retinal Layer Thickness and Reflectance at Different Stages of Diabetic Retinopathy by En Face Optical Coherence Tomography

PubMed Central

Wanek, Justin; Blair, Norman P.; Chau, Felix Y.; Lim, Jennifer I.; Leiderman, Yannek I.; Shahidi, Mahnaz

2016-01-01

Purpose This article reports a method for en face optical coherence tomography (OCT) imaging and quantitative assessment of alterations in both thickness and reflectance of individual retinal layers at different stages of diabetic retinopathy (DR). Methods High-density OCT raster volume scans were acquired in 29 diabetic subjects divided into no DR (NDR) or non-proliferative DR (NPDR) groups and 22 control subjects (CNTL). A customized image segmentation method identified eight retinal layer interfaces and generated en face thickness maps and reflectance images for nerve fiber layer (NFL), ganglion cell and inner plexiform layers (GCLIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor outer segment layer (OSL), and retinal pigment epithelium (RPE). Mean thickness and intensity values were calculated in nine macular subfields for each retinal layer. Results En face thickness maps and reflectance images of retinal layers in CNTL subjects corresponded to normal retinal anatomy. Total retinal thickness correlated negatively with age in nasal subfields (R ≤−0.31; P ≤ 0.03, N = 51). In NDR subjects, NFL and OPL thickness were decreased (P = 0.05), and ONL thickness was increased (P = 0.04) compared to CNTL. In NPDR subjects, GCLIPL thickness was increased in perifoveal subfields (P < 0.05) and INL intensity was higher in all macular subfields (P = 0.04) compared to CNTL. Conclusions Depth and spatially resolved retinal thickness and reflectance measurements are potential biomarkers for assessment and monitoring of DR. PMID:27409491

Retinal single-layer analysis with optical coherence tomography shows inner retinal layer thinning in Huntington's disease as a potential biomarker.

PubMed

Gulmez Sevim, Duygu; Unlu, Metin; Gultekin, Murat; Karaca, Cagatay

2018-02-12

There have been ongoing clinical trials of therapeutic agents in Huntington's disease (HD) which requires development of reliable biomarkers of disease progression. There have been studies in the literature with conflicting results on the involvement of retina in HD, and up to date there is not a study evaluating the single retinal layers in HD. We aimed to evaluate the specific retinal changes in HD and their usability as potential disease progression markers. This cross-sectional study used spectral-domain optical coherence tomography with automatic segmentation to measure peripapillary retinal nerve fiber layer (pRNFL) thickness and the thickness and volume of retinal layers in foveal scans of 15 patients with HD and 15 age- and sex-matched controls. Genetic testing results, disease duration, HD disease burden scores and Unified HD Rating Scales motor scores were acquired for the patients. Temporal pRNFL, macular RNFL (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer and outer plexiform layer thicknesses and IPL, retinal pigment epithelium and outer macular volume were found lower in HD compared to controls, while outer nuclear layer and outer retinal layer thickness were increased (p < 0.05). We found significant correlations between inner retinal layer thicknesses, most significantly with mRNFL and GCL and disease progression markers. The outcomes of this study points out that retinal layers, most significantly mRNFL and GCL, are strongly correlated with the disease progression in HD and could serve as useful biomarkers for disease progression.

Diagnostic Accuracy of Spectralis SD OCT Automated Macular Layers Segmentation to Discriminate Normal from Early Glaucomatous Eyes.

PubMed

Pazos, Marta; Dyrda, Agnieszka Anna; Biarnés, Marc; Gómez, Alicia; Martín, Carlos; Mora, Clara; Fatti, Gianluca; Antón, Alfonso

2017-08-01

To evaluate the accuracy of the macular retinal layer segmentation software of the Spectralis spectral-domain (SD) optical coherence tomography (OCT) device (Heidelberg Engineering, Inc., Heidelberg, Germany) to discriminate between healthy and early glaucoma (EG) eyes. Prospective, cross-sectional study. Forty EG eyes and 40 healthy controls were included. All participants were examined using the standard posterior pole and the peripapillary retinal nerve fiber layer (pRNFL) protocols of the Spectralis OCT device. Using an Early Treatment Diagnostic Retinopathy Study circle at the macular level, the automated retinal segmentation software was applied to determine thicknesses of the following parameters: total retinal thickness, inner retinal layer (IRL), macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer (mGCL), macular inner plexiform layer (mIPL), macular inner nuclear layer (mINL), macular outer plexiform layer (mOPL), macular outer nuclear layer (mONL), photoreceptors (PR), and retinal pigmentary epithelium (RPE). The ganglion cell complex (GCC) was determined by adding the mRNFL, mGCL, and mIPL parameters and the ganglion cell layer-inner plexiform layer (mGCL-IPL) was determined by combining the mGCL and mIPL parameters. Thickness of each layer was compared between the groups, and the layer and sector with the best area under the receiver operating characteristic curve (AUC) were identified. Comparison of pRNFL, IRL, mRNFL, mGCL, mIPL, mGCC, mGCL-IPL, mINL, mOPL, mONL, PR, and RPE parameters and total retinal thicknesses between groups for the different areas and their corresponding AUCs. Peripapillary RNFL was significantly thinner in the EG group globally and in all 6 sectors assessed (P < 0.0005). For the macular variables, retinal thickness was significantly reduced in the EG group for total retinal thickness, mIRL, mRNFL, mGCL, and mIPL. The 2 best isolated parameters to discriminate between the 2 groups were pRNFL (AUC, 0.956) and mRNFL (AUC, 0.906). When mRNFL, mGCL, and mIPL measurements were combined (mGCC and mGCL plus mIPL), then its diagnostic performance improved (AUC, 0.940 and 0.952, respectively). Macular RNFL, mGCL-IPL, and mGCC measurements showed a high diagnostic capability to discriminate between healthy and EG participants. However, macular intraretinal measurements still have not overcome standard pRNFL parameters. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Multicenter reliability of semiautomatic retinal layer segmentation using OCT

PubMed Central

Oberwahrenbrock, Timm; Traber, Ghislaine L.; Lukas, Sebastian; Gabilondo, Iñigo; Nolan, Rachel; Songster, Christopher; Balk, Lisanne; Petzold, Axel; Paul, Friedemann; Villoslada, Pablo; Brandt, Alexander U.; Green, Ari J.

2018-01-01

Objective To evaluate the inter-rater reliability of semiautomated segmentation of spectral domain optical coherence tomography (OCT) macular volume scans. Methods Macular OCT volume scans of left eyes from 17 subjects (8 patients with MS and 9 healthy controls) were automatically segmented by Heidelberg Eye Explorer (v1.9.3.0) beta-software (Spectralis Viewing Module v6.0.0.7), followed by manual correction by 5 experienced operators from 5 different academic centers. The mean thicknesses within a 6-mm area around the fovea were computed for the retinal nerve fiber layer, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer (OPL), and outer nuclear layer (ONL). Intraclass correlation coefficients (ICCs) were calculated for mean layer thickness values. Spatial distribution of ICC values for the segmented volume scans was investigated using heat maps. Results Agreement between raters was good (ICC > 0.84) for all retinal layers, particularly inner retinal layers showed excellent agreement across raters (ICC > 0.96). Spatial distribution of ICC showed highest values in the perimacular area, whereas the ICCs were poorer for the foveola and the more peripheral macular area. The automated segmentation of the OPL and ONL required the most correction and showed the least agreement, whereas differences were less prominent for the remaining layers. Conclusions Automated segmentation with manual correction of macular OCT scans is highly reliable when performed by experienced raters and can thus be applied in multicenter settings. Reliability can be improved by restricting analysis to the perimacular area and compound segmentation of GCL and IPL. PMID:29552598

Alterations in NMDA receptor expression during retinal degeneration in the RCS rat.

PubMed

Gründer, T; Kohler, K; Guenther, E

2001-01-01

To determine how a progressive loss of photoreceptor cells and the concomitant loss of glutamatergic input to second-order neurons can affect inner-retinal signaling, glutamate receptor expression was analyzed in the Royal College of Surgeons (RCS) rat, an animal model of retinitis pigmentosa. Immunohistochemistry was performed on retinal sections of RCS rats and congenic controls between postnatal (P) day 3 and the aged adult (up to P350) using specific antibodies against N-methyl-D-aspartate (NMDA) subunits. All NMDA subunits (NR1, NR2A-2D) were expressed in control and dystrophic retinas at all ages, and distinct patterns of labeling were found in horizontal cells, subpopulations of amacrine cells and ganglion cells, as well as in the outer and inner plexiform layer (IPL). NRI immunoreactivity in the inner plexiform layer of adult control retinas was concentrated in two distinct bands, indicating a synaptic localization of NMDA receptors in the OFF and ON signal pathways. In the RCS retina, these bands of NRI immunoreactivity in the IPL were much weaker in animals older than P40. In parallel, NR2B immunoreactivity in the outer plexiform layer (OPL) of RCS rats was always reduced compared to controls and vanished between P40 and P120. The most striking alteration observed in the degenerating retina, however, was a strong expression of NRI immunoreactivity in Müller cell processes in the inner retina which was not observed in control animals and which was present prior to any visible sign of photoreceptor degeneration. The results suggest functional changes in glutamatergic receptor signaling in the dystrophic retina and a possible involvement of Müller cells in early processes of this disease.

Evaluation of Macular Ganglion Cell-inner Plexiform Layer and Choroid in Psoriasis Patients Using Enhanced Depth Imaging Spectral Domain Optical Coherence Tomography.

PubMed

Ersan, Ismail; Kilic, Sevilay; Arikan, Sedat; Kara, Selcuk; Işik, Selda; Gencer, Baran; Ogretmen, Zerrin

2017-08-01

To evaluate changes in the thickness of the central macula, macular ganglion cell-inner plexiform layer (mGCIPL), and subfoveal choroid in patients with psoriasis using spectral domain optical coherence tomography (SD-OCT). The measurements of macular, mGCIPL thicknesses and subfoveal choroidal thickness (SFCT) obtained by SD-OCT of psoriasis patients (n = 46). These measurements were compared with those of 50 healthy controls. The macular, mGCIPL, and choroidal thicknesses did not differ between the controls and psoriatic subjects (p>0.05). When the patients were divided into two distinct groups, only the SFCT was significantly thicker in the severe psoriasis group compared with the mild psoriasis group (p = 0.003). These findings suggest that choroidal alterations are seen without macular changes in patients with psoriasis. Severe psoriasis appears to be related to increases in SFCT as a consequence of possible inflammatory cascades that are part of the disease's pathogenesis.

Diagnostic ability of macular ganglion cell inner plexiform layer measurements in glaucoma using swept source and spectral domain optical coherence tomography.

PubMed

Yang, Zhiyong; Tatham, Andrew J; Weinreb, Robert N; Medeiros, Felipe A; Liu, Ting; Zangwill, Linda M

2015-01-01

To evaluate the diagnostic ability of macular ganglion cell and inner plexiform layer measurements in glaucoma, obtained using swept source (SS) and spectral domain (SD) optical coherence tomography (OCT) and to compare to circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. The study included 106 glaucomatous eyes of 80 subjects and 41 eyes of 22 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Macular ganglion cell and inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and cpRNFL thickness were assessed using SS-OCT and SD-OCT, and area under the receiver operating characteristic curves (AUCs) were calculated to determine ability to differentiate glaucomatous and healthy eyes and between early glaucomatous and healthy eyes. Mean (± standard deviation) mGCIPL and mGCC thickness were thinner in both healthy and glaucomatous eyes using SS-OCT compared to using SD-OCT. Fixed and proportional biases were detected between SS-OCT and SD-OCT measures. Diagnostic accuracy (AUCs) for differentiating between healthy and glaucomatous eyes for average and sectoral mGCIPL was similar in SS-OCT (0.65 to 0.81) and SD-OCT (0.63 to 0.83). AUCs for average cpRNFL acquired using SS-OCT and SD-OCT tended to be higher (0.83 and 0.85, respectively) than for average mGCC (0.82 and 0.78, respectively), and mGCIPL (0.73 and 0.75, respectively) but these differences did not consistently reach statistical significance. Minimum SD-OCT mGCIPL and mGCC thickness (unavailable in SS-OCT) had the highest AUC (0.86) among macular measurements. Assessment of mGCIPL thickness using SS-OCT or SD-OCT is useful for detecting glaucomatous damage, but measurements are not interchangeable for patient management decisions. Diagnostic accuracies of mGCIPL and mGCC from both SS-OCT and SD-OCT were similar to that of cpRNFL for glaucoma detection.

Validity of the temporal-to-nasal macular ganglion cell-inner plexiform layer thickness ratio as a diagnostic parameter in early glaucoma.

PubMed

Park, Jung-Won; Jung, Hyun-Ho; Heo, Hwan; Park, Sang-Woo

2015-08-01

To evaluate the diagnostic validity of temporal-to-nasal macular ganglion cell-inner plexiform layer thickness (TNM) ratio using Cirrus high definition-optical coherence tomography (HD-OCT) in patients with early glaucomatous damage. Enrolled participants included 130 normal controls, 50 patients with preperimetric glaucoma and 106 patients with early glaucoma. The patients with early glaucoma were classified into two subgroups according to the pattern of the visual field (VF) defects: the paracentral scotoma (PCS, n = 54) and the peripheral scotoma (PPS, n = 52). The thickness of the macular ganglion cell-inner plexiform layer (mGCIPL) and circumpapillary retinal nerve fibre layer (cpRNFL) was measured by Cirrus HD-OCT, and the average, superior and inferior TNM ratio was calculated. The average TNM ratio is a sum of superotemporal and inferotemporal mGCIPL thicknesses divided by the sum of superonasal and inferonasal mGCIPL thicknesses. Area under the receiver operating characteristic curve (AROC) of each parameter was compared between the groups. The parameter with the best AROC was the average TNM ratio and inferotemporal mGCIPL thickness in the PCS group and average cpRNFL thickness in the PPS group. The AROCs of the average, superior and inferior TNM ratio (p < 0.001, p = 0.007 and p < 0.001, respectively), minimum, average, inferotemporal and inferior mGCIPL thickness (p = 0.004, p = 0.003, p = 0.002 and p = 0.001, respectively) of the PCS were significantly higher than those of the PPS. However, the AROCs of the all cpRNFL thickness parameters did not show statistically significant differences between two subgroups. Asymmetry of temporal-to-nasal mGCIPL thickness could be an important parameter in the diagnosis of early glaucoma with paracentral VF defects. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Diagnostic Ability of Macular Ganglion Cell Inner Plexiform Layer Measurements in Glaucoma Using Swept Source and Spectral Domain Optical Coherence Tomography

PubMed Central

Yang, Zhiyong; Tatham, Andrew J.; Weinreb, Robert N.; Medeiros, Felipe A.; Liu, Ting; Zangwill, Linda M.

2015-01-01

Purpose To evaluate the diagnostic ability of macular ganglion cell and inner plexiform layer measurements in glaucoma, obtained using swept source (SS) and spectral domain (SD) optical coherence tomography (OCT) and to compare to circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements. Methods The study included 106 glaucomatous eyes of 80 subjects and 41 eyes of 22 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Macular ganglion cell and inner plexiform layer (mGCIPL), macular ganglion cell complex (mGCC) and cpRNFL thickness were assessed using SS-OCT and SD-OCT, and area under the receiver operating characteristic curves (AUCs) were calculated to determine ability to differentiate glaucomatous and healthy eyes and between early glaucomatous and healthy eyes. Results Mean (± standard deviation) mGCIPL and mGCC thickness were thinner in both healthy and glaucomatous eyes using SS-OCT compared to using SD-OCT. Fixed and proportional biases were detected between SS-OCT and SD-OCT measures. Diagnostic accuracy (AUCs) for differentiating between healthy and glaucomatous eyes for average and sectoral mGCIPL was similar in SS-OCT (0.65 to 0.81) and SD-OCT (0.63 to 0.83). AUCs for average cpRNFL acquired using SS-OCT and SD-OCT tended to be higher (0.83 and 0.85, respectively) than for average mGCC (0.82 and 0.78, respectively), and mGCIPL (0.73 and 0.75, respectively) but these differences did not consistently reach statistical significance. Minimum SD-OCT mGCIPL and mGCC thickness (unavailable in SS-OCT) had the highest AUC (0.86) among macular measurements. Conclusion Assessment of mGCIPL thickness using SS-OCT or SD-OCT is useful for detecting glaucomatous damage, but measurements are not interchangeable for patient management decisions. Diagnostic accuracies of mGCIPL and mGCC from both SS-OCT and SD-OCT were similar to that of cpRNFL for glaucoma detection. PMID:25978420

Abundance and ultrastructural diversity of neuronal gap junctions in the OFF and ON sublaminae of the inner plexiform layer of rat and mouse retina.

PubMed

Kamasawa, N; Furman, C S; Davidson, K G V; Sampson, J A; Magnie, A R; Gebhardt, B R; Kamasawa, M; Yasumura, T; Zumbrunnen, J R; Pickard, G E; Nagy, J I; Rash, J E

2006-11-03

Neuronal gap junctions are abundant in both outer and inner plexiform layers of the mammalian retina. In the inner plexiform layer (IPL), ultrastructurally-identified gap junctions were reported primarily in the functionally-defined and anatomically-distinct ON sublamina, with few reported in the OFF sublamina. We used freeze-fracture replica immunogold labeling and confocal microscopy to quantitatively analyze the morphologies and distributions of neuronal gap junctions in the IPL of adult rat and mouse retina. Under "baseline" conditions (photopic illumination/general anesthesia), 649 neuronal gap junctions immunogold-labeled for connexin36 were identified in rat IPL, of which 375 were photomapped to OFF vs. ON sublaminae. In contrast to previous reports, the volume-density of gap junctions was equally abundant in both sublaminae. Five distinctive morphologies of gap junctions were identified: conventional crystalline and non-crystalline "plaques" (71% and 3%), plus unusual "string" (14%), "ribbon" (7%) and "reticular" (2%) forms. Plaque and reticular gap junctions were distributed throughout the IPL. However, string and ribbon gap junctions were restricted to the OFF sublamina, where they represented 48% of gap junctions in that layer. In string and ribbon junctions, curvilinear strands of connexons were dispersed over 5 to 20 times the area of conventional plaques having equal numbers of connexons. To define morphologies of gap junctions under different light-adaptation conditions, we examined an additional 1150 gap junctions from rats and mice prepared after 30 min of photopic, mesopic and scotopic illumination, with and without general anesthesia. Under these conditions, string and ribbon gap junctions remained abundant in the OFF sublamina and absent in the ON sublamina. Abundant gap junctions in the OFF sublamina of these two rodents with rod-dominant retinas revealed previously-undescribed but extensive pathways for inter-neuronal communication; and the wide dispersion of connexons in string and ribbon gap junctions suggests unique structural features of gap junctional coupling in the OFF vs. ON sublamina.

Age-Related Alterations in the Retinal Microvasculature, Microcirculation, and Microstructure.

PubMed

Wei, Yantao; Jiang, Hong; Shi, Yingying; Qu, Dongyi; Gregori, Giovanni; Zheng, Fang; Rundek, Tatjana; Wang, Jianhua

2017-07-01

To characterize age-related alterations in the retinal microcirculation, microvascular network, and microstructure in healthy subjects. Seventy-four healthy subjects aged from 18 to 82 years were recruited and divided into four age groups (G1 with age <35 years, G2 with age 35 ∼ 49 years, G3 with age 50 ∼ 64 years, and G4 with age ≥65 years). Custom ultra-high resolution optical coherence tomography (UHR-OCT) was used to acquire six intraretinal layers of the macula. OCT angiography (OCTA) was used to image the retinal microvascular network. The retinal blood flow velocity (BFV) was measured using a Retinal Function Imager (RFI). Compared to G1, G2 had significant thinning of the retinal nerve fiber layer (RNFL) (P < 0.05), while G3 had thinning of the RNFL and ganglion cell and inner plexiform layer (GCIPL) (P < 0.05), in addition to thickening of the outer plexiform layer (OPL) and photoreceptor layer (PR) (P < 0.05). G4 had loss in retinal vessel density, thinning in RNFL and GCIPL, and decrease in venular BFV, in addition to thickening of the OPL and PR (P < 0.05). Age was negatively related to retinal vessel densities, the inner retinal layers, and venular BFV (P < 0.05). By contrast, age was positively related to OPL and PR (P < 0.05). During aging, decreases in retinal vessel density, inner retinal layer thickness, and venular BFV were evident and impacted each other as observed by simultaneous changes in multiple retinal components.

Ontogenetic expression of the vanilloid receptors TRPV1 and TRPV2 in the rat retina.

PubMed

Leonelli, Mauro; Martins, Daniel O; Kihara, Alexandre H; Britto, Luiz R G

2009-11-01

The present study aimed to analyze the gene and protein expression and the pattern of distribution of the vanilloid receptors TRPV1 and TRPV2 in the developing rat retina. During the early phases of development, TRPV1 was found mainly in the neuroblastic layer of the retina and in the pigmented epithelium. In the adult, TRPV1 was found in microglial cells, blood vessels, astrocytes and in neuronal structures, namely synaptic boutons of both retinal plexiform layers, as well as in cell bodies of the inner nuclear layer and the ganglion cell layer. The pattern of distribution of TRPV1 was mainly punctate, and there was higher TRPV1 labeling in the peripheral retina than in central regions. TRPV2 expression was quite distinct. Its expression was virtually undetectable by immunoblotting before P1, and that receptor was found by immunohistochemistry only by postnatal day 15 (P15). RNA and protein analysis showed that the adult levels are only reached by P60, which includes small processes in the retinal plexiform layers, and labeled cellular bodies in the inner nuclear layer and the ganglion cell layer. There was no overlapping between the signal observed for both receptors. In conclusion, our results showed that the patterns of distribution of TRPV1 and TRPV2 are different during the development of the rat retina, suggesting that they have specific roles in both visual processing and in providing specific cues to neural development.

Retina-Inspired Filter.

PubMed

Doutsi, Effrosyni; Fillatre, Lionel; Antonini, Marc; Gaulmin, Julien

2018-07-01

This paper introduces a novel filter, which is inspired by the human retina. The human retina consists of three different layers: the Outer Plexiform Layer (OPL), the inner plexiform layer, and the ganglionic layer. Our inspiration is the linear transform which takes place in the OPL and has been mathematically described by the neuroscientific model "virtual retina." This model is the cornerstone to derive the non-separable spatio-temporal OPL retina-inspired filter, briefly renamed retina-inspired filter, studied in this paper. This filter is connected to the dynamic behavior of the retina, which enables the retina to increase the sharpness of the visual stimulus during filtering before its transmission to the brain. We establish that this retina-inspired transform forms a group of spatio-temporal Weighted Difference of Gaussian (WDoG) filters when it is applied to a still image visible for a given time. We analyze the spatial frequency bandwidth of the retina-inspired filter with respect to time. It is shown that the WDoG spectrum varies from a lowpass filter to a bandpass filter. Therefore, while time increases, the retina-inspired filter enables to extract different kinds of information from the input image. Finally, we discuss the benefits of using the retina-inspired filter in image processing applications such as edge detection and compression.

Evaluation of white matter hyperintensities and retinal fiber layer, ganglion cell layer, inner-plexiform layer, and choroidal layer in migraine patients.

PubMed

Tak, Ali Zeynel Abidin; Sengul, Yıldızhan; Bilak, Şemsettin

2018-03-01

The aim of our study is to assess retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), inner-plexiform layer (IPL), and choroidal layer in migraine patients with white matter lesion (WML) or without WML, using spectral domain optical coherence tomography (OCT). To our study, 77 migraine patients who are diagnosed with migraine in accordance to the International Classification of Headache Disorders (ICHD)-3 beta and 43 healthy control are included. In accordance to cranial MRI, migraine patients are divided into two groups as those who have white matter lesions (39 patients), and those who do not have a lesion (38 patients). OCT was performed for participants. The average age of participants was comparable. The RNFL average thickness parameter in the migraine group was significantly lower than in the control group (p < 0.01). However, no significant difference was detected among those migraine patients who have WML, and those who do not have. No significant difference is detected among all groups in terms of IPL, GCL, and choroidal layer measuring scales. The proofs showing that affected retinal nerve fiber layer are increased in migraine patients. However, it is not known whether this may affect other layers of retina, or whether there is a correlation between affected retinal structures and white matter lesions. In our study, we found thinner RNFL in migraine patients when we compared with controls but IPL, GCL, and choroid layer values were similar between each patient groups and controls. Also, all parameters were similar between patients with WML and without WML. Studies in this regard are required.

Ulex europaeus I and glycine max bind to the human olfactory bulb.

PubMed

Nagao, M; Oka, N; Kamo, H; Akiguchi, I; Kimura, J

1993-12-24

The distribution of binding sites for the fucose-selective lectin Ulex europaeus I and the terminal N-acetylgalactosamine-selective lectin glycine max in the human olfactory bulb were studied. These lectins bound to primary olfactory axons in the olfactory nerve layer and the glomerular layer. They also bound to fibers located in the deeper layers such as the external plexiform layer and the granular layer. Furthermore they projected to the olfactory stalk but not in the cerebrum. The deeper projections of the lectin binding fibers may affect the function of the olfactory bulb in humans.

A Framework for Modeling Competitive and Cooperative Computation in Retinal Processing

NASA Astrophysics Data System (ADS)

Moreno-Díaz, Roberto; de Blasio, Gabriel; Moreno-Díaz, Arminda

2008-07-01

The structure of the retina suggests that it should be treated (at least from the computational point of view), as a layered computer. Different retinal cells contribute to the coding of the signals down to ganglion cells. Also, because of the nature of the specialization of some ganglion cells, the structure suggests that all these specialization processes should take place at the inner plexiform layer and they should be of a local character, prior to a global integration and frequency-spike coding by the ganglion cells. The framework we propose consists of a layered computational structure, where outer layers provide essentially with band-pass space-time filtered signals which are progressively delayed, at least for their formal treatment. Specialization is supposed to take place at the inner plexiform layer by the action of spatio-temporal microkernels (acting very locally), and having a centerperiphery space-time structure. The resulting signals are then integrated by the ganglion cells through macrokernels structures. Practically all types of specialization found in different vertebrate retinas, as well as the quasilinear behavior in some higher vertebrates, can be modeled and simulated within this framework. Finally, possible feedback from central structures is considered. Though their relevance to retinal processing is not definitive, it is included here for the sake of completeness, since it is a formal requisite for recursiveness.

Immunolocalization of ciliary neurotrophic factor receptor alpha (CNTFRalpha) in mammalian photoreceptor cells.

PubMed

Beltran, William A; Rohrer, Hermann; Aguirre, Gustavo D

2005-04-01

To characterize the site of expression of the alpha subunit of the receptor for ciliary neurotrophic factor (CNTFRalpha) in the retina of a variety of mammalian species, and determine whether CNTFRalpha is localized to photoreceptor cells. The cellular distribution of CNTFRalpha(protein) was examined by immunocytochemistry in the adult retinas of several mammalian species that included mouse, rat, dog, cat, sheep, pig, horse, monkey, and human. Developing retinas from 3-day-old and 6-day-old rats were also included in this study. The molecular weight of CNTFRalpha in rat, dog, cat, pig, and human retinas was determined by immunoblotting. CNTFRalpha immunolabeling was present in the retina of all species. A common pattern was observed in all species, and represented labeling of the nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer plexiform layer (OPL). CNTFRalpha did not immunolocalize to photoreceptor cells in both adult and developing rodent retinas, but was consistently observed in both rods and cones of non-rodent species. The molecular weight of CNTFRalpha in mammalian retinas was approximately 61-64 kDa. These findings highlight a significant difference in the expression of CNTFRalpha in the retina of rodent and non-rodent mammalian species. The expression of CNTFRalpha by rods and cones in non-rodent species may suggest a direct mechanism of action if CNTF administration results in photoreceptor rescue.

Morphometric studies of heavy ion damage in the brains of rodents

NASA Technical Reports Server (NTRS)

Kraft, L. M.; Cox, A. B.

1986-01-01

The relative biological effectiveness (RBE) of different heavy ions for the mammalian brain was determined in mice irradiated at 100 days of age with He-4, C-12, Ne-20, Fe-56, Ar-40, or Co-60 gamma photons (with the primary particle LET values ranging from 2 to 650). Brain preparations were examined 16 months later for volume changes in the external plexiform layer (P-zone) of the olfactory bulb and an internal region (G-zone), which consists of the granule cells, the internal plexiform layer, and the mitral cell layer. The result indicate that the volume changes did occur in the olfactory bulb, not only in absolute terms but also when expressed as the ratio of the structures to each other and to the bulb as a whole. While the observed increased neuronal loss in mice receiving 700 cGy of Co-60 support the earlier data from irradiated rabbits, the increases observed in bulbar volumes and in the volume ratios of the P and the G zones measured in the mice given lower doses (320 or 160 cGy of He or C), were not expected.

The role of cell body density in ruminant retina mechanics assessed by atomic force and Brillouin microscopy

NASA Astrophysics Data System (ADS)

Weber, Isabell P.; Yun, Seok Hyun; Scarcelli, Giuliano; Franze, Kristian

2017-12-01

Cells in the central nervous system (CNS) respond to the stiffness of their environment. CNS tissue is mechanically highly heterogeneous, thus providing motile cells with region-specific mechanical signals. While CNS mechanics has been measured with a variety of techniques, reported values of tissue stiffness vary greatly, and the morphological structures underlying spatial changes in tissue stiffness remain poorly understood. We here exploited two complementary techniques, contact-based atomic force microscopy and contact-free Brillouin microscopy, to determine the mechanical properties of ruminant retinae, which are built up by different tissue layers. As in all vertebrate retinae, layers of high cell body densities (‘nuclear layers’) alternate with layers of low cell body densities (‘plexiform layers’). Different tissue layers varied significantly in their mechanical properties, with the photoreceptor layer being the stiffest region of the retina, and the inner plexiform layer belonging to the softest regions. As both techniques yielded similar results, our measurements allowed us to calibrate the Brillouin microscopy measurements and convert the Brillouin shift into a quantitative assessment of elastic tissue stiffness with optical resolution. Similar as in the mouse spinal cord and the developing Xenopus brain, we found a strong correlation between nuclear densities and tissue stiffness. Hence, the cellular composition of retinae appears to strongly contribute to local tissue stiffness, and Brillouin microscopy shows a great potential for the application in vivo to measure the mechanical properties of transparent tissues.

Age-Related Alterations in the Retinal Microvasculature, Microcirculation, and Microstructure

PubMed Central

Wei, Yantao; Jiang, Hong; Shi, Yingying; Qu, Dongyi; Gregori, Giovanni; Zheng, Fang; Rundek, Tatjana; Wang, Jianhua

2017-01-01

Purpose To characterize age-related alterations in the retinal microcirculation, microvascular network, and microstructure in healthy subjects. Methods Seventy-four healthy subjects aged from 18 to 82 years were recruited and divided into four age groups (G1 with age <35 years, G2 with age 35 ∼ 49 years, G3 with age 50 ∼ 64 years, and G4 with age ≥65 years). Custom ultra-high resolution optical coherence tomography (UHR-OCT) was used to acquire six intraretinal layers of the macula. OCT angiography (OCTA) was used to image the retinal microvascular network. The retinal blood flow velocity (BFV) was measured using a Retinal Function Imager (RFI). Results Compared to G1, G2 had significant thinning of the retinal nerve fiber layer (RNFL) (P < 0.05), while G3 had thinning of the RNFL and ganglion cell and inner plexiform layer (GCIPL) (P < 0.05), in addition to thickening of the outer plexiform layer (OPL) and photoreceptor layer (PR) (P < 0.05). G4 had loss in retinal vessel density, thinning in RNFL and GCIPL, and decrease in venular BFV, in addition to thickening of the OPL and PR (P < 0.05). Age was negatively related to retinal vessel densities, the inner retinal layers, and venular BFV (P < 0.05). By contrast, age was positively related to OPL and PR (P < 0.05). Conclusions During aging, decreases in retinal vessel density, inner retinal layer thickness, and venular BFV were evident and impacted each other as observed by simultaneous changes in multiple retinal components. PMID:28744554

Organisation and tyrosine hydroxylase and calretinin immunoreactivity in the main olfactory bulb of paca (Cuniculus paca): a large caviomorph rodent.

PubMed

Sasahara, Tais Harumi de Castro; Leal, Leonardo Martins; Spillantini, Maria Grazia; Machado, Márcia Rita Fernandes

2015-04-01

The majority of neuroanatomical and chemical studies of the olfactory bulb have been performed in small rodents, such as rats and mice. Thus, this study aimed to describe the organisation and the chemical neuroanatomy of the main olfactory bulb (MOB) in paca, a large rodent belonging to the Hystricomorpha suborder and Caviomorpha infraorder. For this purpose, histological and immunohistochemical procedures were used to characterise the tyrosine hydroxylase (TH) and calretinin (CR) neuronal populations and their distribution. The paca MOB has eight layers: the olfactory nerve layer (ONL), the glomerular layer (GL), the external plexiform layer (EPL; subdivided into the inner and outer sublayers), the mitral cell layer (MCL), the internal plexiform layer (IPL), the granule cell layer (GCL), the periventricular layer and the ependymal layer. TH-ir neurons were found mostly in the GL, and moderate numbers of TH-ir neurons were scattered in the EPL. Numerous varicose fibres were distributed in the IPL and in the GCL. CR-ir neurons concentrated in the GL, around the base of the olfactory glomeruli. Most of the CR-ir neurons were located in the MCL, IPL and GCL. Some of the granule cells had an apical dendrite with a growth cone. The CR immunoreactivity was also observed in the ONL with olfactory nerves strongly immunostained. This study has shown that the MOB organisation in paca is consistent with the description in other mammals. The characterisation and distribution of the population of TH and CR in the MOB is not exclusively to this species. This large rodent shares common patterns to other caviomorph rodent, as guinea pig, and to the myomorph rodents, as mice, rats and hamsters.

Association of the AMPA receptor-related postsynaptic density proteins GRIP and ABP with subsets of glutamate-sensitive neurons in the rat retina.

PubMed

Gábriel, Robert; de Souza, Sunita; Ziff, Edward B; Witkovsky, Paul

2002-07-22

We used specific antibodies against two postsynaptic density proteins, GRIP (glutamate receptor interacting protein) and ABP (AMPA receptor-binding protein), to study their distribution in the rat retina. In the central nervous system, it has been shown that both proteins bind strongly to the AMPA glutamate receptor (GluR) 2/3 subunits, but not other GluRs, through a set of three PDZ domains. Western blots detected a single GRIP protein that was virtually identical in retina and brain, whereas retinal ABP corresponded to only one of three ABP peptides found in brain. The retinal distributions of GluR2/3, GRIP, and ABP immunoreactivity (IR) were similar but not identical. GluR2/3 immunoreactivity (IR) was abundant in both plexiform layers and in large perikarya. ABP IR was concentrated in large perikarya but was sparse in the plexiform layers, whereas GRIP IR was relatively more abundant in the plexiform layers than in perikarya. Immunolabel for these three antibodies consisted of puncta < or = 0.2 microm in diameter. The cellular localization of GRIP and ABP IR was examined by double labeling subclasses of retinal neuron with characteristic marker proteins, e.g., calbindin. GRIP, ABP, and GluR2/3 IR were detected in horizontal cells, dopaminergic and glycinergic AII amacrine cells and large ganglion cells. Immunolabel was absent in rod bipolar and weak or absent in cholinergic amacrine cells. By using the tyramide method of signal amplification, a colocalization of GluR2/3 was found with either GRIP or ABP in horizontal cell terminals, and perikarya of amacrine and ganglion cells. Our results show that ABP and GRIP colocalize with GluR2/3 in particular subsets of retinal neuron, as was previously established for certain neurons in the brain. Copyright 2002 Wiley-Liss, Inc.

Diagnostic Value of Ganglion Cell-Inner Plexiform Layer Thickness in Glaucoma With Superior or Inferior Visual Hemifield Defects.

PubMed

Kim, Ho Soong; Yang, Heon; Lee, Tae Heon; Lee, Kyung Heon

2016-06-01

To determine the diagnostic value of the ganglion cell-inner plexiform layer (GCIPL) thickness in glaucomatous eyes with superior or inferior visual hemifield defects. Eighty-five patients with glaucoma (42 isolated superior hemifield defects and 43 isolated inferior hemifield defects) and 46 normal subjects were enrolled. All patients underwent Cirrus high-definition optical coherence tomography and standard automated perimetry. The area under the receiver operating characteristic curve (AUC) was calculated to determine the diagnostic ability of the GCIPL and peripapillary retinal nerve fiber layer (pRNFL). In the superior hemifield defect glaucoma group, the best parameters for discriminating normal eyes from glaucomatous eyes were the inferotemporal GCIPL thickness (0.942), inferior quadrant RNFL thickness (0.974), and 7 o'clock sector RNFL thickness (0.999). For diagnosing inferior hemifield defect glaucoma, the AUCs of all GCIPL parameters (0.331 to 0.702) were significantly lower than that of the superior quadrant RNFL thickness (0.866, P<0.05). The diagnostic ability of GCIPL parameters was similar to that of the pRNFL parameters in superior hemifield defect glaucoma. However, the diagnostic performance of the GCIPL parameters was significantly inferior to those of the pRNFL parameters in eyes with inferior hemifield defect glaucoma.

A cascade model of information processing and encoding for retinal prosthesis.

PubMed

Pei, Zhi-Jun; Gao, Guan-Xin; Hao, Bo; Qiao, Qing-Li; Ai, Hui-Jian

2016-04-01

Retinal prosthesis offers a potential treatment for individuals suffering from photoreceptor degeneration diseases. Establishing biological retinal models and simulating how the biological retina convert incoming light signal into spike trains that can be properly decoded by the brain is a key issue. Some retinal models have been presented, ranking from structural models inspired by the layered architecture to functional models originated from a set of specific physiological phenomena. However, Most of these focus on stimulus image compression, edge detection and reconstruction, but do not generate spike trains corresponding to visual image. In this study, based on state-of-the-art retinal physiological mechanism, including effective visual information extraction, static nonlinear rectification of biological systems and neurons Poisson coding, a cascade model of the retina including the out plexiform layer for information processing and the inner plexiform layer for information encoding was brought forward, which integrates both anatomic connections and functional computations of retina. Using MATLAB software, spike trains corresponding to stimulus image were numerically computed by four steps: linear spatiotemporal filtering, static nonlinear rectification, radial sampling and then Poisson spike generation. The simulated results suggested that such a cascade model could recreate visual information processing and encoding functionalities of the retina, which is helpful in developing artificial retina for the retinally blind.

ABUNDANCE AND ULTRASTRUCTURAL DIVERSITY OF NEURONAL GAP JUNCTIONS IN THE OFF AND ON SUBLAMINAE OF THE INNER PLEXIFORM LAYER OF RAT AND MOUSE RETINA

PubMed Central

KAMASAWA, N.; FURMAN, C. S.; DAVIDSON, K. G. V.; SAMPSON, J. A.; MAGNIE, A. R.; GEBHARDT, B. R.; KAMASAWA, M.; YASUMURA, T.; ZUMBRUNNEN, J. R.; PICKARD, G. E.; NAGY, J. I.; RASH, J. E.

2007-01-01

Neuronal gap junctions are abundant in both outer and inner plexiform layers of the mammalian retina. In the inner plexiform layer (IPL), ultrastructurally-identified gap junctions were reported primarily in the functionally-defined and anatomically-distinct ON sublamina, with few reported in the OFF sublamina. We used freeze-fracture replica immunogold labeling and confocal microscopy to quantitatively analyze the morphologies and distributions of neuronal gap junctions in the IPL of adult rat and mouse retina. Under “baseline” conditions (photopic illumination/general anesthesia), 649 neuronal gap junctions immunogold-labeled for connexin36 were identified in rat IPL, of which 375 were photomapped to OFF vs. ON sublaminae. In contrast to previous reports, the volume-density of gap junctions was equally abundant in both sublaminae. Five distinctive morphologies of gap junctions were identified: conventional crystalline and non-crystalline “plaques” (71% and 3%), plus unusual “string” (14%), “ribbon” (7%) and “reticular” (2%) forms. Plaque and reticular gap junctions were distributed throughout the IPL. However, string and ribbon gap junctions were restricted to the OFF sublamina, where they represented 48% of gap junctions in that layer. In string and ribbon junctions, curvilinear strands of connexons were dispersed over 5 to 20 times the area of conventional plaques having equal numbers of connexons. To define morphologies of gap junctions under different light-adaptation conditions, we examined an additional 1150 gap junctions from rats and mice prepared after 30 min of photopic, mesopic and scotopic illumination, with and without general anesthesia. Under these conditions, string and ribbon gap junctions remained abundant in the OFF sublamina and absent in the ON sublamina. Abundant gap junctions in the OFF sublamina of these two rodents with rod-dominant retinas revealed previously-undescribed but extensive pathways for inter-neuronal communication; and the wide dispersion of connexons in string and ribbon gap junctions suggests unique structural features of gap junctional coupling in the OFF vs. ON sublamina. PMID:17010526

Autoradiographic identification of acetylcholine in the rabbit retina

PubMed Central

1979-01-01

Rabbit retinas were studied in vitro under conditions known to maintain their physiological function. Retinas incubated in the presence of [3H]choline synthesized substantial amounts of both [3H]phosphorylcholine and [3H]acetylcholine. With time, [3H]phosphorylcholine proceeded into phospholipids, primarily phosphatidylcholine. Retinas pulse-labeled by a 15-min exposure to 0.3 microM [3H]choline were incubated for a subsequent hour under chase conditions designed either to retain newly synthesized acetylcholine within synapses or to promote its release. At the end of this time the two groups of retinas were found to contain equal amounts of radioactivity in the phospholipid pathway, but only the retinas incubated under the acetylcholine-protecting conditions contained [3H]acetylcholine. Freeze-dried, vacuum-embedded tissue from each retina was autoradiographed on dry emulsion. All retinas showed silver grains over the photoreceptor cells and faint labeling of all ganglion cells. In the retinas that contained [3H]acetylcholine, silver grains also accumulated densely over a few cells with the position of amacrine cells, over a subset of the cells of the ganglion cell layer, and in two bands over the inner plexiform layer. Fixation of the retina with aqueous osmium tetroxide retained only the radioactive compounds located in the photoreceptor and ganglion cells. Sections from freeze- dried tissue lost their water-soluble choline metabolites when exposed to water, and autoradiography of such sections again revealed radioactivity primarily in the photoreceptor and ganglion cells. Radioactive compounds extracted from the sections were found to faithfully reflect those present in the tissue before processing; analysis of the compounds eluted from sections microdissected along the outer plexiform layer showed [3H]acetylcholine to have been synthesized only by cells of the inner retina. Taken together, these results indicate that the photoreceptor and ganglion cells are distinguished by a rapid synthesis of choline-containing phospholipids, while acetylcholine synthesis is restricted to a few cells at both margins of the inner plexiform layer. They imply that the only neurons to release acetylcholine within the rabbit retina are a small group of probable amacrine cells. PMID:92476

Profile and Determinants of Retinal Optical Intensity in Normal Eyes with Spectral Domain Optical Coherence Tomography.

PubMed

Chen, Binyao; Gao, Enting; Chen, Haoyu; Yang, Jianling; Shi, Fei; Zheng, Ce; Zhu, Weifang; Xiang, Dehui; Chen, Xinjian; Zhang, Mingzhi

2016-01-01

To investigate the profile and determinants of retinal optical intensity in normal subjects using 3D spectral domain optical coherence tomography (SD OCT). A total of 231 eyes from 231 healthy subjects ranging in age from 18 to 80 years were included and underwent a 3D OCT scan. Forty-four eyes were randomly chosen to be scanned by two operators for reproducibility analysis. Distribution of optical intensity of each layer and regions specified by the Early Treatment of Diabetic Retinopathy Study (ETDRS) were investigated by analyzing the OCT raw data with our automatic graph-based algorithm. Univariate and multivariate analyses were performed between retinal optical intensity and sex, age, height, weight, spherical equivalent (SE), axial length, image quality, disc area and rim/disc area ratio (R/D area ratio). For optical intensity measurements, the intraclass correlation coefficient of each layer ranged from 0.815 to 0.941, indicating good reproducibility. Optical intensity was lowest in the central area of retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer and photoreceptor layer, except for the retinal pigment epithelium (RPE). Optical intensity was positively correlated with image quality in all retinal layers (0.553<β<0.851, p<0.01), and negatively correlated with age in most retinal layers (-0.362<β<-0.179, p<0.01), except for the RPE (β = 0.456, p<0.01), outer nuclear layer and photoreceptor layer (p>0.05). There was no relationship between retinal optical intensity and sex, height, weight, SE, axial length, disc area and R/D area ratio. There was a specific pattern of distribution of retinal optical intensity in different regions. The optical intensity was affected by image quality and age. Image quality can be used as a reference for normalization. The effect of age needs to be taken into consideration when using OCT for diagnosis.

Population-based evaluation of retinal nerve fiber layer, retinal ganglion cell layer, and inner plexiform layer as a diagnostic tool for glaucoma.

PubMed

Springelkamp, Henriët; Lee, Kyungmoo; Wolfs, Roger C W; Buitendijk, Gabriëlle H S; Ramdas, Wishal D; Hofman, Albert; Vingerling, Johannes R; Klaver, Caroline C W; Abràmoff, Michael D; Jansonius, Nomdo M

2014-11-20

We determined the glaucoma screening performance of regional optical coherence tomography (OCT) layer thickness measurements in the peripapillary and macular region, in a population-based setting. Subjects (n = 1224) in the Rotterdam Study underwent visual field testing (Humphrey Field Analyzer) and OCT of the macula and optic nerve head (Topcon 3-D OCT-1000). We determined the mean thicknesses of the retinal nerve fiber layer (RNFL), retinal ganglion cell layer (RGCL), and inner plexiform layer for regions-of-interest; thus, defining a series of OCT parameters, using the Iowa Reference Algorithms. Reference standard was the presence of glaucomatous visual field loss (GVFL); controls were subjects without GVFL, an intraocular pressure (IOP) of 21 mm Hg or less, and no positive family history for glaucoma. We calculated the area under the receiver operating characteristics curve (AUCs) and the sensitivity at 97.5% specificity for each parameter. After excluding 23 subjects with an IOP > 21 mm Hg and 73 subjects with a positive family history for glaucoma, there were 1087 controls and 41 glaucoma cases. Mean RGCL thickness in the inferior half of the macular region showed the highest AUC (0.85; 95% confidence interval [CI] 0.77-0.92) and sensitivity (53.7%; 95% CI, 38.7-68.0%). The mean thickness of the peripapillary RNFL had an AUC of 0.77 (95% CI, 0.69-0.85) and a sensitivity of 24.4% (95% CI, 13.7-39.5%). Macular RGCL loss is at least as common as peripapillary RNFL abnormalities in population-based glaucoma cases. Screening for glaucoma using OCT-derived regional thickness identifies approximately half of those cases of glaucoma as diagnosed by perimetry. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Human Chorioretinal Layer Thicknesses Measured in Macula-wide, High-Resolution Histologic Sections

PubMed Central

Messinger, Jeffrey D.; Sloan, Kenneth R.; Mitra, Arnab; McGwin, Gerald; Spaide, Richard F.

2011-01-01

Purpose. To provide a comprehensive description of chorioretinal layer thicknesses in the normal human macula, including two-layer pairs that can produce a combined signal in some optical coherence tomography (OCT) devices (ganglion cell [GCL] and inner plexiform [IPL] layers and outer plexiform [OPL] and outer nuclear [ONL] layers). Methods. In 0.8-μm-thick, macula-wide sections through the foveola of 18 donors (age range, 40–92 years), 21 layers were measured at 25 locations by a trained observer and validated by a second observer. Tissue volume changes were assessed by comparing total retinal thickness in ex vivo OCT and in sections. Results. Median tissue shrinkage was 14.5% overall and 29% in the fovea. Histologic laminar boundaries resembled those in SD-OCT scans, but the shapes of the foveolar OPL and ONL differed. Histologic GCL, IPL, and OPLHenle were thickest at 0.8. to 1, 1.5, and 0.4 mm eccentricity, respectively. ONL was thickest in an inward bulge at the foveal center. At 1 mm eccentricity, GCL, INL, and OPLHenle represented 17.3% to 21.1%, 18.0% to 18.5%, and 14.2% to 16.6% of total retinal thickness, respectively. In donors ≥70 years of age, the RPE and choroid were 17.1% and 29.6% thinner and OPLHenle was 20.8% thicker than in donors <70 years. Conclusions. In this study, the first graphic representation and thickness database of chorioretinal layers in normal macula were generated. Newer OCT systems can separate GCL from IPL and OPLHenle from ONL, with good agreement for the proportion of retinal thickness occupied by OPLHenle in OCT and histology. The thickening of OPLHenle in older eyes may reflect Müller cell hypertrophy associated with rod loss. PMID:21421869

Selective Thinning of the Perifoveal Inner Retina as an Early Sign of Hydroxychloroquine Retinal Toxicity

PubMed Central

Pasadhika, Sirichai; Fishman, Gerald A; Choi, Dongseok; Shahidi, Mahnaz

2013-01-01

Purpose To evaluate macular thickness profiles using spectral-domain optical coherence tomography (SDOCT) and image segmentation in patients with chronic exposure to hydroxychloroquine. Methods This study included 8 patients with chronic exposure to hydroxychloroquine (Group 1) and 8 controls (Group 2). Group 1 patients had no clinically-evident retinal toxicity. All subjects underwent SDOCT imaging of the macula. An image segmentation technique was used to measure thickness of 6 retinal layers at 200 µm intervals. A mixed-effects model was used for multivariate analysis. Results By measuring total retinal thickness either at the central macular (2800 µm in diameter), the perifoveal region 1200-µm-width ring surrounding the central macula), or the overall macular area (5200 µm in diameter), there were no significant differences in the thickness between Groups 1 and 2. On an image segmentation analysis, selective thinning of the inner plexiform + ganglion cell layers (p=0.021) was observed only in the perifoveal area of the patients in Group 1 compared to that of Group 2 by using the mixed-effects model analysis. Conclusions Our results suggest that chronic exposure to hydroxychloroquine is associated with thinning of the perifoveal inner retinal layers, especially in the ganglion cell and inner plexiform layers, even in the absence of functional or structural clinical changes involving the photoreceptor or retinal pigment epithelial cell layers. This may be a contributing factor as the reason most patients who have early detectable signs of drug toxicity present with paracentral or pericentral scotomas. PMID:20395978

The structure and function of the macula in patients with advanced retinitis pigmentosa.

PubMed

Vámos, Rita; Tátrai, Erika; Németh, János; Holder, Graham E; DeBuc, Delia Cabrera; Somfai, Gábor Márk

2011-10-28

To assess the structure and function of the macula in advanced retinitis pigmentosa (RP). Twenty-nine eyes of 22 patients with RP were compared against 17 control eyes. Time-domain optical coherence tomography (OCT) data were processed using OCTRIMA (optical coherence tomography retinal image analysis) as a means of quantifying commercial OCT system images. The thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer complex (GCL+IPL), inner nuclear layer and outer plexiform layer complex (INL+OPL), and the outer nuclear layer (ONL) were measured. Multifocal electroretinography (mfERG) was performed; two groups were formed based on the mfERG findings. Fourteen eyes had no detectable central retinal function (NCRF) on mfERG; detectable but abnormal retinal function (DRF) was present in the mfERG of the other 15 eyes. The thickness of the ONL in the central macular region was significantly less in the NCRF eyes compared with that in both DRF eyes and controls. The ONL was significantly thinner in the pericentral region in both patient groups compared with that in controls, whereas the thickness of the GCL+IPL and INL+OPL was significantly decreased only in the NCRF eyes. The RNFL in the peripheral region was significantly thicker, whereas the thickness of the GCL+IPL and ONL was significantly thinner in both patient groups compared with that in controls. The results are consistent with degeneration of the outer retina preceding inner retinal changes in RP. OCT image segmentation enables objective evaluation of retinal structural changes in RP, with potential use in the planning of therapeutic interventions and conceivably as an outcome measure.

The Structure and Function of the Macula in Patients with Advanced Retinitis Pigmentosa

PubMed Central

Vámos, Rita; Tátrai, Erika; Németh, János; Holder, Graham E.; DeBuc, Delia Cabrera

2011-01-01

Purpose. To assess the structure and function of the macula in advanced retinitis pigmentosa (RP). Methods. Twenty-nine eyes of 22 patients with RP were compared against 17 control eyes. Time-domain optical coherence tomography (OCT) data were processed using OCTRIMA (optical coherence tomography retinal image analysis) as a means of quantifying commercial OCT system images. The thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer complex (GCL+IPL), inner nuclear layer and outer plexiform layer complex (INL+OPL), and the outer nuclear layer (ONL) were measured. Multifocal electroretinography (mfERG) was performed; two groups were formed based on the mfERG findings. Fourteen eyes had no detectable central retinal function (NCRF) on mfERG; detectable but abnormal retinal function (DRF) was present in the mfERG of the other 15 eyes. Results. The thickness of the ONL in the central macular region was significantly less in the NCRF eyes compared with that in both DRF eyes and controls. The ONL was significantly thinner in the pericentral region in both patient groups compared with that in controls, whereas the thickness of the GCL+IPL and INL+OPL was significantly decreased only in the NCRF eyes. The RNFL in the peripheral region was significantly thicker, whereas the thickness of the GCL+IPL and ONL was significantly thinner in both patient groups compared with that in controls. Conclusions. The results are consistent with degeneration of the outer retina preceding inner retinal changes in RP. OCT image segmentation enables objective evaluation of retinal structural changes in RP, with potential use in the planning of therapeutic interventions and conceivably as an outcome measure. PMID:21948552

THICKNESS OF THE MACULA, RETINAL NERVE FIBER LAYER, AND GANGLION CELL-INNER PLEXIFORM LAYER IN THE AGE-RELATED MACULAR DEGENERATION: The Repeatability Study of Spectral Domain Optical Coherence Tomography.

PubMed

Shin, Il-Hwan; Lee, Woo-Hyuk; Lee, Jong-Joo; Jo, Young-Joon; Kim, Jung-Yeul

2018-02-01

To determine the repeatability of measuring the thickness of the central macula, retinal nerve fiber layer, and ganglion cell-inner plexiform layer (GC-IPL) using spectral domain optical coherence tomography (Cirrus HD-OCT) in eyes with age-related macular degeneration. One hundred and thirty-four eyes were included. The measurement repeatability was assessed by an experienced examiner who performed two consecutive measurements using a 512 × 128 macular cube scan and a 200 × 200 optic disk cube scan. To assess changes in macular morphology in patients with age-related macular degeneration, the patients were divided into the following three groups according to the central macular thickness (CMT): A group, CMT < 200 μm; B group, 200 μm ≤ CMT < 300 μm; and C group, CMT > 300 μm. Measurement repeatability was assessed using test-retest variability, a coefficient of variation, and an intraclass correlation coefficient. The mean measurement repeatability for the central macular, retinal nerve fiber layer, and GC-IPL thickness was high in the B group. The mean measurement repeatability for both the central macula and retinal nerve fiber layer thickness was high in the A and C groups, but was lower for the GC-IPL thickness. The measurement repeatability for GC-IPL thickness was high in the B group, but low in the A group and in the C group. The automated measurement repeatability for GC-IPL thickness was significantly lower in patients with age-related macular degeneration with out of normal CMT range. The effect of changes in macular morphology should be considered when analyzing GC-IPL thicknesses in a variety of ocular diseases.

Physiological modeling for detecting degree of perception of a color-deficient person.

PubMed

Rajalakshmi, T; Prince, Shanthi

2017-04-01

Physiological modeling of retina plays a vital role in the development of high-performance image processing methods to produce better visual perception. People with normal vision have an ability to discern different colors. The situation is different in the case of people with color blindness. The aim of this work is to develop a human visual system model for detecting the level of perception of people with red, green and blue deficiency by considering properties like luminance, spatial and temporal frequencies. Simulation results show that in the photoreceptor, outer plexiform and inner plexiform layers, the energy and intensity level of the red, green and blue component for a normal person is proved to be significantly higher than for dichromats. The proposed method explains with appropriate results that red and blue color blindness people could not perceive red and blue color completely.

Simple explant culture of the embryonic chicken retina with long-term preservation of photoreceptors.

PubMed

Thangaraj, Gopenath; Greif, Alexander; Layer, Paul G

2011-10-01

Structurally stable in vitro-model systems are indispensible to analyse neural development during embryogenesis, follow cellular differentiation and evaluate neurotoxicological or growth factor effects. Here we describe a three-dimensional, long-term in vitro-culture system of the embryonic chick retina which supports photoreceptor development. Retinal tissue was isolated from E6 chick eye, and cultured as explants by continuous orbital rotation to allow free floatation without any supporting materials. Young stage (E6) immature retinas were cultured for various time periods in order to follow the differentiation of cell types and plexiform layers by immunocytochemical methods. These explants could be cultured for at least 2-3 weeks with remarkable retention of retinal architecture. Interestingly, photoreceptors developed in the absence of pigment epithelium. Electron microscopic studies revealed formation of structures resembling photoreceptor outer segments, a feature not reported previously. Thus, the verification of photoreceptors, Müller cells, inner retinal cells and the inner plexiform layer described in our study establishes this explant culture as a valuable in vivo-like model system. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Modulation of dendrodendritic interactions and mitral cell excitability in the mouse accessory olfactory bulb by vaginocervical stimulation.

PubMed

Otsuka, T; Ishii, K; Osako, Y; Okutani, F; Taniguchi, M; Oka, T; Kaba, H

2001-05-01

When female mice are mated, they form a memory to the pheromonal signal of their male partner. The neural changes underlying this memory occur in the accessory olfactory bulb, depend upon vaginocervical stimulation at mating and involve changes at the reciprocal synapses between mitral and granule cells. However, the action of vaginocervical stimulation on the reciprocal interactions between mitral and granule cells remains to be elucidated. We have examined the effects of vaginocervical stimulation on paired-pulse depression of amygdala-evoked field potentials recorded in the external plexiform layer of the accessory olfactory bulb (AOB) and the single-unit activity of mitral cells antidromically stimulated from the amygdala in urethane-anaesthetized female mice. Artificial vaginocervical stimulation reduced paired-pulse depression (considered to be due to feedback inhibition of the mitral cell dendrites from the granule cells via reciprocal dendrodendritic synapses) recorded in the AOB external plexiform layer. As would be expected from this result, vaginocervical stimulation also enhanced the spontaneous activity of a proportion of the mitral cells tested. These results suggest that vaginocervical stimulation reduces dendrodendritic feedback inhibition to mitral cells and enhances their activity.

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

On the distributive patterns of ATPase activity and its functional significance in retinae of certain birds.

PubMed

Tewari, H B; Tyagi, H R

1977-01-01

The present study incorporates the details of distribution of adenosine triphosphatase amongst the various constituents of retinae of Passer, Psittacula, Streptopelia and Athene. The outer segments in all the cases are intensely positive for the enzyme. This is the part where the light strikes first and initiates the visual processes. The nuclear layers are also positive for the enzyme activity. It is interesting to note that inner plexiform layers show clear-out demarcations of various sub-synaptic layers in all the birds except Psittacula. The ganglion cells and optic nerve fibres are also positive for the enzyme.

The retina of the shovel-nosed ray, Rhinobatos batillum (Rhinobatidae): morphology and quantitative analysis of the ganglion, amacrine and bipolar cell populations.

PubMed

Collin, S P

1988-01-01

A light microscopy study of the retina of the shovel-nosed ray, Rhinobatos batillum (Rhinobatidae) has revealed a duplex retina with a rod to cone ratio between 4:1 and 6:1. The inner nuclear layer consists of three layers of large horizontal cells, tightly packed, stellate bipolar cells, and up to three substrata of amacrine cells. The collaterals of the many supporting Müller cells project from the inner to the outer limiting membrane and divide the retina into many subunits. The cells of the ganglion cell layer are distributed into two layers, although a large proportion of ganglion cells are also displaced into the inner plexiform and inner nuclear layers. Topographic analysis of the cells in the ganglion cell layer, inner plexiform and inner nuclear layers reveals a number of regional specializations or "areae centrales". Ganglion cells were retrogradely-labelled with cobalt-lysine from the optic nerve, and three sub-populations of neurons characterized on their soma size and position. Small (20-50 microns2), large (80-300 microns2) and giant (greater than 300 microns2) sub-populations of ganglion cells each revealed distinct retinal specializations with peak densities of 3 x 10(3), 1.25 x 10(3) and 1.57 x 10(3) cells per mm2, respectively. Topographical comparison between Nissl-stained and retrogradely-labelled ganglion cell populations have established that a maximum of 20% in the "area centralis", and 75% in unspecialized, peripheral regions of the retina are non-ganglion cells. Out of a total of 210,566 cells in the ganglion cell layer, 49% were found to be non-ganglion cells. Iso-density contour maps of amacrine and bipolar cell distributions also reveal some specializations. These cell concentrations lie in corresponding regions to areas of increased density in the large and giant ganglion cell populations, suggesting some functional association.

ON Cone Bipolar Cell Axonal Synapses in the OFF Inner Plexiform Layer of the Rabbit Retina

PubMed Central

Lauritzen, J. Scott; Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Mohammed, Shoeb; Hoang, John V.; Marc, Robert E.

2012-01-01

Analysis of the rabbit retinal connectome RC1 reveals that the division between the ON and OFF inner plexiform layer (IPL) is not structurally absolute. ON cone bipolar cells make non-canonical axonal synapses onto specific targets and receive amacrine cell synapses in the nominal OFF layer, creating novel motifs, including inhibitory crossover networks. Automated transmission electron microscope (ATEM) imaging, molecular tagging, tracing, and rendering of ≈ 400 bipolar cells reveals axonal ribbons in 36% of ON cone bipolar cells, throughout the OFF IPL. The targets include GABA-positive amacrine cells (γACs), glycine-positive amacrine cells (GACs) and ganglion cells. Most ON cone bipolar cell axonal contacts target GACs driven by OFF cone bipolar cells, forming new architectures for generating ON-OFF amacrine cells. Many of these ON-OFF GACs target ON cone bipolar cell axons, ON γACs and/or ON-OFF ganglion cells, representing widespread mechanisms for OFF to ON crossover inhibition. Other targets include OFF γACs presynaptic to OFF bipolar cells, forming γAC-mediated crossover motifs. ON cone bipolar cell axonal ribbons drive bistratified ON-OFF ganglion cells in the OFF layer and provide ON drive to polarity-appropriate targets such as bistratified diving ganglion cells (bsdGCs). The targeting precision of ON cone bipolar cell axonal synapses shows that this drive incidence is necessarily a joint distribution of cone bipolar cell axonal frequency and target cell trajectories through a given volume of the OFF layer. Such joint distribution sampling is likely common when targets are sparser than sources and when sources are coupled, as are ON cone bipolar cells. PMID:23042441

Localization of α1-2 Fucose Glycan in the Mouse Olfactory Pathway.

PubMed

Kondoh, Daisuke; Kamikawa, Akihiro; Sasaki, Motoki; Kitamura, Nobuo

2017-01-01

Glycoconjugates in the olfactory system play critical roles in neuronal formation, and α1-2 fucose (α1-2Fuc) glycan mediates neurite outgrowth and synaptic plasticity. Histochemical findings of α1-2Fuc glycan in the mouse olfactory system detected using Ulex europaeus agglutinin-I (UEA-I) vary. This study histochemically assessed the main olfactory and vomeronasal pathways in male and female ICR and C57BL/6J mice aged 3-4 months using UEA-I. Ulex europaeus agglutinin-I reacted with most receptor cells arranged mainly at the basal region of the olfactory epithelium. The olfactory nerve layer and glomerular layer of the main olfactory bulb were speckled with positive UEA-I staining, and positive fibers were scattered from the glomerular to the internal plexiform layer. The lateral olfactory tract and rostral migratory stream were also positive for UEA-I. We identified superficial short-axon cells, interneurons of the external plexiform layer, external, middle and internal tufted cells, mitral cells and granule cells as the origins of the UEA-I-positive fibers in the main olfactory bulb. The anterior olfactory nucleus, anterior piriform cortex and olfactory tubercle were negative for UEA-I. Most receptor cells in the vomeronasal epithelium and most glomeruli of the accessory olfactory bulb were positive for UEA-I. Our findings indicated that α1-2Fuc glycan is located within the primary and secondary, but not the ternary, pathways of the main olfactory system, in local circuits of the main olfactory bulb and within the primary, but not secondary, pathway of the vomeronasal system. © 2016 S. Karger AG, Basel.

Histologic development of the human fovea from midgestation to maturity.

PubMed

Hendrickson, Anita; Possin, Daniel; Vajzovic, Lejla; Toth, Cynthia A

2012-11-01

To describe the histologic development of the human central retina from fetal week (Fwk) 22 to 13 years. Retrospective observational case series. Retinal layers and neuronal substructures were delineated on foveal sections of fixed tissue stained in azure II-methylene blue and on frozen sections immunolabeled for cone, rod, or glial proteins. Postmortem tissue was from 11 eyes at Fwk 20-27; 8 eyes at Fwk 28-37; 6 eyes at postnatal 1 day to 6 weeks; 3 eyes at 9 to 15 months; and 5 eyes at 28 months to 13 years. At Fwk 20-22 the fovea could be identified by the presence of a single layer of cones in the outer nuclear layer. Immunolabeling detected synaptic proteins, cone and rod opsins, and Müller glial processes separating the photoreceptors. The foveal pit appeared at Fwk 25, involving progressive peripheral displacement of ganglion cell, inner plexiform, and inner nuclear layers. The pit became wider and shallower after birth, and appeared mature by 15 months. Between Fwk 25 and Fwk 38, all photoreceptors developed more distinct inner and outer segments, but these were longer on peripheral than foveal cones. After birth the foveal outer nuclear layer became much thicker as cone packing occurred. Cone packing and neuronal migration during pit formation combined to form long central photoreceptor axons, which changed the outer plexiform layer from a thin sheet of synaptic pedicles into the thickest layer in the central retina by 15 months. Foveal inner and outer segment length matched peripheral cones by 15 months and was 4 times longer by 13 years. These data are necessary to understand the marked changes in human retina from late gestation to early adulthood. They provide qualitative and quantitative morphologic information required to interpret the changes in hyper- and hyporeflexive bands in pediatric spectral-domain optical coherence tomography images at the same ages. Copyright © 2012 Elsevier Inc. All rights reserved.

Evaluation of Retinal Changes in Progressive Supranuclear Palsy and Parkinson Disease.

PubMed

Gulmez Sevim, Duygu; Unlu, Metin; Gultekin, Murat; Karaca, Cagatay; Mirza, Meral; Mirza, Galip Ertugrul

2018-06-01

Differentiating Parkinson disease (PD) from progressive supranuclear palsy (PSP) can be challenging early in the clinical course. The aim of our study was to see if specific retinal changes could serve as a distinguishing feature. We used spectral domain optical coherence tomography (SD-OCT) with automatic segmentation to measure peripapillary nerve fiber layer thickness and the thickness and volume of retinal layers at the macula. Thicknesses of superior peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer, inner plexiform layer, inner nuclear layer, and macular volume were more affected in PSP compared with PD (P < 0.05). Thicker inferotemporal pRNFL and lower macular volume were detected in levodopa users compared with nonusers in patients with PD. PD and PSP are associated with distinct changes in retinal morphology, which can be assessed with SD-OCT.

Mechanisms of Retinal Damage from Chronic Laser Radiation.

DTIC Science & Technology

1981-07-01

culture. The pigment epithelium is deter- mined to be almost equally susceptible to damage in vitro as in vivo and the same action spectrum is similar in...92 -97 D. Experiment III. Light Damage in Culture of Bovine Retinal Pigment Epithelium 1. Methodology a. Collection of Cells... epithelium : Mild form of damage. Figure 18 Inner segments severely damaged. Figure 19 : Cone pedicle after exposure. Figure 20 Outer plexiform layer

Morphometric studies of heavy ion damage in the brains of rodents

NASA Astrophysics Data System (ADS)

Kraft, L. M.; Cox, A. B.

As an approach to determining the relative biological effectiveness (RBE) of each of five different heavy ions for the mammalian brain, histological preparations of brains from mice exposed to various HZE particles at different doses and primary LET∞ values were examined by means of semi-automated image analysis for volume changes in specific regions of the olfactory bulb. The mice were irradiated at 100 days of age and euthanatized about 500 days (16 months) later. Exposures were: 60Co gamma photons (LET∞ = 1-2 keV/μm), 4He (LET∞ = 6 keV/μm, 12C (LET∞ = 80 keV/μm), 20Ne (LET∞ = 150 keV/μm, 56Fe (LET∞ = 180 keV/μm, and 40Ar (LET∞ = 650 keV/μm). Animals receiving particle radiation were exposed in an extended Bragg peak region except for iron where the plateau region was used. The zones measured in the olfactory bulb were 1) the external plexiform layer (zone) and 2) an internal region consisting of the granule cells, internal plexiform layer, and layer of mitral cells. These studies indicated that volume changes did indeed occur, not only in absolute terms but alos when expressed as the ratio of the structures to each other and to the bulb as a whole. Although this study is exploratory in character, the data obtained may nevertheless contribute to a determination of risk factors due to late effects from HZE particles.

Accumulation of neurocan, a brain chondroitin sulfate proteoglycan, in association with the retinal vasculature in RCS rats.

PubMed

Zhang, Yiqin; Rauch, Uwe; Perez, Maria-Thereza R

2003-03-01

To examine whether and how the retinal distribution of the chondroitin sulfate proteoglycan neurocan is affected after photoreceptor cell loss and whether it correlates with the multiple secondary cellular changes that accompany the photoreceptor degeneration. Retinas from normal rats (Sprague-Dawley; postnatal days [P]0-P70), RCS rats with dystrophic retinas (P0-P300), RCS-rdy(+) congenic rats with nondystrophic retinas (P0-202), and rhodopsin mutant rats, P23H (P0-P257) and S334ter (P0-P220), were processed for immunohistochemistry using a polyclonal antibody to rat neurocan. The overall distribution of neurocan was similar in all retinas examined. Neurocan immunostaining was detected over the nerve fiber layer, the plexiform layers, the photoreceptor outer segments region, and the ciliary epithelium. With age, labeling throughout the plexiform layers decreased continuously. In RCS rats however, conspicuous labeling was also seen in association with retinal vessels, from P15 onward. Accumulation of neurocan in association with the retinal vasculature does not correlate with photoreceptor cell loss, because it was not observed in the rhodopsin mutant rats. During the earliest stages of the disease, accumulation of debris in the subretinal space in RCS rats may be sufficient per se to initiate a cascade of metabolic changes that result in accumulation of neurocan. With time, the neurocan accumulated perivascularly may, by interaction with other matrix molecules, modulate at least some of the vascular alterations observed in this animal model.

Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity

PubMed Central

Esquiva, Gema; Avivi, Aaron; Hannibal, Jens

2016-01-01

The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer nuclear layer (ONL), an outer plexiform layer (OPL), an inner nuclear layer (INL), an inner plexiform layer (IPL), and a ganglion cell layer (GCL). By immunohistochemistry, the number of melanopsin (mRGCs) and non-melanopsin bearing retinal ganglion cells was analyzed in detail. Using the ganglion cell marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 ± 62 RGCs. Of these, 87% (752 ± 40) contain melanopsin (cell density 788 melanopsin RGCs/mm2). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly in the GCL with projections forming two dendritic plexuses located in the inner part of the IPL and in the OPL. Few melanopsin dendrites were also found in the ONL. The Spalax retina is rich in rhodopsin and long/middle wave (L/M) cone opsin bearing photoreceptor cells. By using Ctbp2 as a marker for ribbon synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells contain calretinin. The calretinin expressing amacrine cells seemed to form synaptic contacts with rhodopsin containing photoreceptor cells in the OPL and contacts with melanopsin cell bodies and dendrites in the IPL. The study demonstrates the complex retinal circuitry used by the Spalax to detect light, and provides evidence for both melanopsin and non-melanopsin projecting pathways to the brain. PMID:27375437

Non-image Forming Light Detection by Melanopsin, Rhodopsin, and Long-Middlewave (L/W) Cone Opsin in the Subterranean Blind Mole Rat, Spalax Ehrenbergi: Immunohistochemical Characterization, Distribution, and Connectivity.

PubMed

Esquiva, Gema; Avivi, Aaron; Hannibal, Jens

2016-01-01

The blind mole rat, Spalax ehrenbergi, can, despite severely degenerated eyes covered by fur, entrain to the daily light/dark cycle and adapt to seasonal changes due to an intact circadian timing system. The present study demonstrates that the Spalax retina contains a photoreceptor layer, an outer nuclear layer (ONL), an outer plexiform layer (OPL), an inner nuclear layer (INL), an inner plexiform layer (IPL), and a ganglion cell layer (GCL). By immunohistochemistry, the number of melanopsin (mRGCs) and non-melanopsin bearing retinal ganglion cells was analyzed in detail. Using the ganglion cell marker RNA-binding protein with multiple splicing (RBPMS) it was shown that the Spalax eye contains 890 ± 62 RGCs. Of these, 87% (752 ± 40) contain melanopsin (cell density 788 melanopsin RGCs/mm(2)). The remaining RGCs were shown to co-store Brn3a and calretinin. The melanopsin cells were located mainly in the GCL with projections forming two dendritic plexuses located in the inner part of the IPL and in the OPL. Few melanopsin dendrites were also found in the ONL. The Spalax retina is rich in rhodopsin and long/middle wave (L/M) cone opsin bearing photoreceptor cells. By using Ctbp2 as a marker for ribbon synapses, both rods and L/M cone ribbons containing pedicles in the OPL were found in close apposition with melanopsin dendrites in the outer plexus suggesting direct synaptic contact. A subset of cone bipolar cells and all photoreceptor cells contain recoverin while a subset of bipolar and amacrine cells contain calretinin. The calretinin expressing amacrine cells seemed to form synaptic contacts with rhodopsin containing photoreceptor cells in the OPL and contacts with melanopsin cell bodies and dendrites in the IPL. The study demonstrates the complex retinal circuitry used by the Spalax to detect light, and provides evidence for both melanopsin and non-melanopsin projecting pathways to the brain.

Normative Database and Color-code Agreement of Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-inner Plexiform Layer Thickness in a Vietnamese Population.

PubMed

Perez, Claudio I; Chansangpetch, Sunee; Thai, Andy; Nguyen, Anh-Hien; Nguyen, Anwell; Mora, Marta; Nguyen, Ngoc; Lin, Shan C

2018-06-05

Evaluate the distribution and the color probability codes of the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thickness in a healthy Vietnamese population and compare them with the original color-codes provided by the Cirrus spectral domain OCT. Cross-sectional study. We recruited non-glaucomatous Vietnamese subjects and constructed a normative database for peripapillary RNFL and macular GCIPL thickness. The probability color-codes for each decade of age were calculated. We evaluated the agreement with Kappa coefficient (κ) between OCT color probability codes with Cirrus built-in original normative database and the Vietnamese normative database. 149 eyes of 149 subjects were included. The mean age of enrollees was 60.77 (±11.09) years, with a mean spherical equivalent of +0.65 (±1.58) D and mean axial length of 23.4 (±0.87) mm. Average RNFL thickness was 97.86 (±9.19) microns and average macular GCIPL was 82.49 (±6.09) microns. Agreement between original and adjusted normative database for RNFL was fair for average and inferior quadrant (κ=0.25 and 0.2, respectively); and good for other quadrants (range: κ=0.63-0.73). For macular GCIPL κ agreement ranged between 0.39 and 0.69. After adjusting with the normative Vietnamese database, the percent of yellow and red color-codes increased significantly for peripapillary RNFL thickness. Vietnamese population has a thicker RNFL in comparison with Cirrus normative database. This leads to a poor color-code agreement in average and inferior quadrant between the original and adjusted database. These findings should encourage to create a peripapillary RNFL normative database for each ethnicity.

Retinal histogenesis in an altricial avian species, the zebra finch (Taeniopygia guttata, Vieillot 1817).

PubMed

Álvarez-Hernán, Guadalupe; Sánchez-Resino, Elena; Hernández-Núñez, Ismael; Marzal, Alfonso; Rodríguez-León, Joaquín; Martín-Partido, Gervasio; Francisco-Morcillo, Javier

2018-07-01

Comparative developmental studies have shown that the retina of altricial fish and mammals is incompletely developed at birth, and that, during the first days of life, maturation proceeds rapidly. In contrast, precocial fish and mammals are born with fully differentiated retinas. Concerning birds, knowledge about retinal development is generally restricted to a single order of precocial birds, Galliformes, due to the fact that both the chicken and the Japanese quail are considered model systems. However, comparison of embryonic pre-hatchling retinal development between altricial and precocial birds has been poorly explored. The purpose of this study was to examine the morphogenesis and histogenesis of the retina in the altricial zebra finch (Taeniopygia guttata, Vieillot 1817) and compare the results with those from previous studies in the precocial chicken. Several maturational features (morphogenesis of the optic vesicle and optic cup, appearance of the first differentiated neurons, the period in which the non-apical cell divisions are observable, and the emergence of the plexiform layers) were found to occur at later stages in the zebra finch than in the chicken. At hatching, the retina of T. guttata showed the typical cytoarchitecture of the mature tissue, although features of immaturity were still observable, such as a ganglion cell layer containing many thick cells, very thin plexiform layers, and poorly developed photoreceptors. Moreover, abundant mitotic activity was detected in the entire retina, even in the regions where the layering was complete. The circumferential marginal zone was very prominent and showed abundant mitotic activity. The partially undifferentiated stage of maturation at hatching makes the T. guttata retina an appropriate model with which to study avian postnatal retinal neurogenesis. © 2018 Anatomical Society.

Connectomic Reconstruction of the Inner Plexiform Layer in the Mouse Retina

DTIC Science & Technology

2013-08-08

PROGRAM ELEMENT NUMBER 611103 6.AUTHORS Sd. PROJECT NUMBER Moritz Helmstaedter, Kevin L. Briggman, Srinivas C . Tw-aga, Viren Jain, H. Sebastian...LIMITATION OF a. REPORT b . ABSTRACT c . THIS PAGE ABSTRACT uu uu uu uu Models, Biological* New-opillphysiology 1S . NUMBER OF PAGES .. 19a. NAME...mouse retina Moritz Helmstaedter1{, Kevin L. Briggman1{, Srinivas C . Turaga2{, Viren Jain2{, H. Sebastian Seung2 & Winfried Denk1 Comprehensivehigh

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath (MPNST) Tumors and Plexiform Neurofibromas (PN)

DTIC Science & Technology

2012-09-01

TITLE: Convection-Enhanced Delivery ( CED ) in an Animal Model of Malignant Peripheral Nerve Sheath ( MPNST ) Tumors and Plexiform Neurofibromas (PN...within the sciatic nerve. 15. SUBJECT TERMS Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform Neurofibromas...determine the distribution of macromolecules delivered to intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural

Histological studies on the telencephalon of Hynobius leechii at the metamorphosis phase and the adult phase.

PubMed

Zhou, Ying-Ying; Shao, Ran; Liang, Chuan-Cheng; Wang, Yong; Wang, Li-Wen

2009-08-01

To investigate the telencephalon developmental characteristics of Hynobius leehii, and enrich the research data of comparable neurobiology and nervous system development of amphibian. HE staining and Nissl staining methods were used to study the telencephalon histological structure of Hynobius leechii at both the metamorphosis and the adult phases, and to explore the developmental phases of telencephalon. The olfactory bulb could be roughly divided into 6 layers from lateral to medial. The lateral cerebral ventricles at the metamorphosis phase were smaller than those at the adult phase, and there were no clear borderlines between the primordial pallium and the primordial hippocampus, or between the primordial pallium and the primordial piriform area. Moreover, the cells in the primordial piriform area were more closely distributed than those in the primordial hippocampus or the primordial pallium. Compared with those at the adult phase, cells in nucleuses at the metamorphosis phase were larger in number and more closely distributed. The telencephalon of Hynobius leehii at the metamorphosis phase has generally formed the adult structure. However, it is still at a transition state of differentiation to maturity during the development of Hynobius leehii.

Trace elements during primordial plexiform network formation in human cerebral organoids

PubMed Central

Sartore, Rafaela C.; Cardoso, Simone C.; Lages, Yury V.M.; Paraguassu, Julia M.; Stelling, Mariana P.; Madeiro da Costa, Rodrigo F.; Guimaraes, Marilia Z.; Pérez, Carlos A.

2017-01-01

Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development in vitro. In the present work, we analyzed cerebral organoids derived from human pluripotent stem cells by synchrotron radiation X-ray fluorescence in order to measure biologically valuable micronutrients incorporated and distributed into the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves P, S, K, Ca, Fe and Zn. Occurrence of different concentration gradients also suggests active regulation of elemental transmembrane transport. Finally, the analysis of pairs of elements shows interesting elemental interaction patterns that change from 30 to 45 days of development, suggesting short- or long-term associations, such as storage in similar compartments or relevance for time-dependent biological processes. These findings shed light on which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood. PMID:28194309

Quercetin protects the retina by reducing apoptosis due to ischemia-reperfusion injury in a rat model.

PubMed

Arikan, Sedat; Ersan, Ismail; Karaca, Turan; Kara, Selcuk; Gencer, Baran; Karaboga, Ihsan; Hasan Ali, Tufan

2015-01-01

This study aimed to investigate the effect of quercetin on apoptotic cell death induced by ischemia-reperfusion (I/R) injury in the rat retina. Twenty-four rats were divided into four equal groups: control, ischemic, solvent, and quercetin. I/R injury was achieved by elevating the intraocular pressure above the perfusion pressure. Intraperitoneal injections of 20 mg/kg of quercetin and dimethyl sulfoxide (DMSO) were performed in the quercetin and solvent groups, respectively, immediately prior to I/R injury, and the researchers allowed for the retinas to be reperfused. Forty-eight hours after injury, the thicknesses of the retinal ganglion cell layer (RGCL), inner nuclear layer (INL), inner plexiform layer (IPL), outer plexiform layer (OPL), and outer nuclear layer (ONL) were measured in all groups. Moreover, the numbers of terminal deoxynucleotidyl transferase dUTP nick-end-labeled [TUNEL (+)] cells and caspase-3 (+) cells in both INL and ONL were evaluated in all groups. The administration of quercetin was found to reduce the thinning of all retinal layers. The mean thickness of INL in the quercetin and ischemic groups was 21 ± 5.6 µm and 16 ± 6.4 µm, respectively (P<0.05). Similarly, the mean thickness of ONL in the quercetin and ischemic groups was 50 ± 12.8 µm and 40 ± 8.7 µm, respectively (P<0.05). The antiapoptotic effect of quercetin in terms of reducing the numbers of both TUNEL (+) cells and caspase-3 (+) cells was significant in INL. The mean number of TUNEL (+) cells in INL in the ischemic and quercetin groups was 476.8 ± 45.6/mm2 and 238.72 ± 251/mm2, respectively (P<0.005). The mean number of caspase-3 (+) cells in INL of ischemic and quercetin groups was 633.6 ± 38.7/mm2 and 342.4 ± 36.1/mm2, respectively (P<0.001). The use of quercetin may be beneficial in the treatment of retinal I/R injury because of its antiapoptotic effect on the retinal layers, particularly in INL.

Comparison of spectral-domain optical coherence tomography for intra-retinal layers thickness measurements between healthy and diabetic eyes among Chinese adults

PubMed Central

Li, Shu-ting; Wang, Xiang-ning; Du, Xin-hua; Wu, Qiang

2017-01-01

Purpose To compare intra-retinal layer thickness measurements between eyes with no or mild diabetic retinopathy (DR) and age-matched controls using Spectralis spectral-domain optical coherence tomography (SD-OCT). Methods Cross-sectional observational analysis study. High-resolution macular volume scans (30° * 25°) were obtained for 133 type 2 diabetes mellitus (T2DM) patients with no DR, 42 T2DM patients with mild DR and 115 healthy controls. The mean thickness was measured in all 9 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors for 8 separate layers, inner retinal layer (IRL), outer retinal layer (ORL) and total retina (TR), after automated segmentation. The ETDRS grid consisted of three concentric circles of 1-, 3-, and 6-mm diameter. The superior, inferior, temporal, and nasal sectors of the 3- and 6-mm circles were respectively designated as S3, I3, T3, and N3 and S6, I6, T6, and N6. Linear regression analyses were conducted to evaluate the associations between the intra-retinal layer thicknesses, age, diabetes duration, fasting blood glucose and HbA1c. Results The mean age and duration of T2DM were 61.1 and 13.7 years, respectively. Although no significant differences in the average TR and ORL volumes were observed among the groups, significant differences were found in the volume and sectorial thicknesses of the inner plexiform layer (IPL), outer plexiform layer (OPL) and IRL among the groups. In particular, the thicknesses of the IPL (S3, T3, S6, I6 and T6 sectors) and the IRL (S6 sector) were decreased in the no-DR group compared with the controls (P < 0.05). The thickness of the OPL (S3, N3, S6 and N6 sectors) was thinner in the no-DR group than in mild DR (P < 0.05). The average IPL thickness was significantly negatively correlated with age and the duration of diabetes. Conclusion The assessment of the intra-retinal layer thickness showed a significant decrease in the IPL and IRL thicknesses in Chinese adults with T2DM, even in the absence of visible microvascular signs of DR. PMID:28493982

Diagnostic ability of macular ganglion cell-inner plexiform layer thickness in glaucoma suspects.

PubMed

Xu, Xiaoyu; Xiao, Hui; Guo, Xinxing; Chen, Xiangxi; Hao, Linlin; Luo, Jingyi; Liu, Xing

2017-12-01

The purpose is to assess the diagnostic ability for early glaucoma of macular ganglion cell-inner plexiform layer (GCIPL) thickness in a Chinese population including glaucoma suspects.A total of 367 eyes with primary open-angle glaucoma (168 early glaucoma, 78 moderate glaucoma, and 121 advanced glaucoma), 52 eyes with ocular hypertension (OHT), 59 eyes with enlarged cup-to-disc ratio (C/D), and 225 normal eyes were included. GCIPL thickness (average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal), retinal nerve fiber layer (RNFL) thickness, and optic nerve head (ONH) parameters were measured using Cirrus high-definition optical coherence tomography (OCT) and compared. The diagnostic ability of OCT parameters was assessed by area under receiver operating characteristic curve (AUROC) in 3 distinguishing groups: normal eyes and eyes with early glaucoma, normal eyes and eyes with glaucoma regardless of disease stage, and nonglaucomatous eyes (normal eyes, eyes with OHT, and enlarged C/D) and early glaucomatous eyes.Glaucomatous eyes showed a significant reduction in GCIPL thickness compared with nonglaucomatous eyes. In all 3 distinguishing groups, best-performing parameters of GCIPL thickness, RNFL thickness, and ONH parameters were minimum GCIPL thickness (expressed in AUROC, 0.899, 0.952, and 0.900, respectively), average RNFL thickness (0.904, 0.953, and 0.892, respectively), and rim area (0.861, 0.925, and 0.824, respectively). There was no statistical significance of AUROC between minimum GCIPL thickness and average RNFL thickness (all P > .05).GCIPL thickness could discriminate early glaucoma from normal and glaucoma suspects with good sensitivity and specificity. The glaucoma diagnostic ability of GCIPL thickness was comparable to that of RNFL thickness. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Diagnostic value of ganglion cell-inner plexiform layer for early detection of ethambutol-induced optic neuropathy.

PubMed

Lee, Ju-Yeun; Han, Jinu; Seo, Jeong Gi; Park, Kyung-Ah; Oh, Sei Yeul

2018-04-26

To evaluate the diagnostic value of macular ganglion cell-inner plexiform layer (mGCIPL) thickness versus peripapillary retinal nerve fibre layer (pRNFL) thickness for the early detection of ethambutol-induced optic neuropathy (EON). Twenty-eight eyes of 15 patients in the EON group and 100 eyes of 53 healthy subjects in the control group were included. All patients with EON demonstrated the onset of visual symptoms within 3 weeks. Diagnostic power for pRNFL and mGCIPL thicknesses measured by Cirrus spectral-domain optical coherence tomography was assessed by area under the receiver operating characteristic (AUROC) curves and sensitivity. All of the mGCIPL thickness measurements were thinner in the EON group than in the control group in early EON (p<0.001). All of pRNFL thicknesses except inferior RNFL showed AUROC curves above 0.5, and all of the mGCIPL thicknesses showed AUROC curves above 0.5. The AUROC of the average mGCIPL (0.812) thickness was significantly greater than that of the average pRNFL (0.507) thickness (p<0.001). Of all the mGCIPL-related parameters considered, the minimum thickness showed the greatest AUROC value (0.863). The average mGCIPL thickness showed a weak correlation with visual field pattern standard deviations (r 2 =0.158, p<0.001). In challenging cases of EON, the mGCIPL thickness has better diagnostic performance in detecting early-onset EON as compared with using pRNFL thickness. Among the early detection ability of mGCIPL thickness, minimum GCIPL thickness has high diagnostic ability. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Opiate and N-methyl-D-aspartate receptors in form-deprivation myopia.

PubMed

Fischer, A J; Seltner, R L; Stell, W K

1998-01-01

Pharmacological studies have implicated retinal opiate pathways in the visual regulation of ocular growth. However, the effects of opiate receptor subtype-specific compounds on form-deprivation myopia (FDM) are inconsistent (Seltner et al., 1997), and may be mediated by non-opiate receptors. The purpose of this study was to test whether opiate receptor-inactive (D-) enantiomers elicit the same FDM-suppressing effect as their opiate receptor-active (L-) counterparts. Since some opiates are thought to act at NMDA receptors, we also tested whether NMDA receptor agonists and antagonists influence ocular growth or FDM. We found that both L- and D- enantiomers of morphine-like compounds (dextrorphanol and levorphanol, and D- and L-naloxone) were equally effective in blocking FDM. The NMDA receptor antagonists dextromethorphan, MK801, and AP5 also suppressed FDM. A single toxic dose of NMDA, that destroys many subtypes of amacrine cells (including those that synthesize the opioid peptide enkephalin), induced myopia and ocular enlargement in ungoggled eyes, and eliminated the ability of form-deprivation to enhance ocular growth. The NR-1 subunit of the NMDA receptor was localized to a narrowly stratified, intense stratum at approximately 50% depth in the inner plexiform layer, diffusely throughout the proximal inner plexiform layer, and to many somata in the amacrine and ganglion cell layers. These observations suggest that most effects of opiate receptor ligands on FDM in the chick are mediated by non-opiate receptors, which are likely to include NMDA receptors. NMDA as an excitotoxin transiently enhances ocular growth, but thereafter disables retinal mechanisms that promote emmetropization and FDM. These observations are consistent with a prominent role for pathways utilizing NMDA receptors in FDM and ocular growth-control.

Benzodiazepine and kainate receptor binding sites in the RCS rat retina.

PubMed

Stasi, Kalliopi; Naskar, Rita; Thanos, Solon; Kouvelas, Elias D; Mitsacos, Ada

2003-02-01

The effect of age and photoreceptor degeneration on the kainate subtype of glutamate receptors and on the benzodiazepine-sensitive gamma-aminobutyric acid-A receptors (GABA(A)) in normal and RCS (Royal College of Surgeons) rats were investigated. [(3)H]Kainate and [(3)H]flunitrazepam were used as radioligands for kainate and GABA(A)/benzodiazepine()receptors, respectively, using the quantitative receptor autoradiography technique. In both normal and RCS rat retina we observed that [(3)Eta]flunitrazepam and [(3)Eta]kainate binding levels were several times higher in inner plexiform layer (IPL) than in outer plexiform layer (OPL) at all four ages studied (P17, P35, P60 and P180). Age-related changes in receptor binding were observed in normal rat retina: [(3)Eta]flunitrazepam binding showed a significant decrease of 25% between P17 and P60 in IPL,and [(3)Eta]kainate binding showed significant decreases between P17 and P35 in both synaptic layers (71% in IPL and 63% in OPL). Degeneration-related changes in benzodiazepine and kainate receptor binding were observed in RCS rat retina. In IPL, [(3)Eta]flunitrazepam and [(3)Eta]kainate binding levels were higher than in normal retina at P35 (by 24% and 86%, respectively). In OPL, [(3)Eta]flunitrazepam binding was higher in RCS than in normal retina on P35 (74%) and also on P60 (62%). The results indicate that postnatal changes occur in kainate and benzodiazepine receptor binding sites in OPL and IPL of the rat retina up to 6 months of age. The data also suggest that the receptor binding changes observed in the RCS retina could be a consequence of the primary photoreceptor degeneration.

Correlation between spectral-domain OCT findings and visual acuity in X-linked retinoschisis.

PubMed

Yang, Hyun Seung; Lee, Jung Bok; Yoon, Young Hee; Lee, Joo Yong

2014-05-08

To investigate the tomographic characteristics of the outer retina and choroid and their relationship with visual acuity in X-linked juvenile retinoschisis (XLRS) patients using spectral-domain optical coherence tomography (SD-OCT). In this retrospective, observational, case-control study, we analyzed 20 eyes of 10 patients with XLRS using SD-OCT. The clinical and tomographic features of the outer retina, including the external limiting membrane (ELM), inner segment/outer segment (IS/OS) junction, cone cell outer segment tips (COST) line, photoreceptor outer segment (PROS) length, and choroid, were evaluated. As controls, 40 age-, sex-, and refraction-matched healthy eyes (1:2 matched) were randomly selected and imaged in parallel. The most prevalent area of abnormality in the outer retina layer of our patients was the outer plexiform layer (OPL; 60% of all affected eyes) and COST line (75% of all affected eyes). On average, the subfoveal choroid and PROS lengths were 35 μm thicker and 19 μm thinner, respectively, in XLRS patients (P = 0.084 and P < 0.001, respectively). A dominant IS/OS junction, COST line defects, and PROS length were related to patient best-corrected visual acuity (BCVA; P = 0.029, P = 0.001, and P < 0.001, respectively) by univariate analysis. Cone cell outer segment tips line defect and PROS length were the only factors related to BCVA in multivariate analysis (P = 0.028 and 0.003, respectively). Outer plexiform layer and photoreceptor microstructure defects are frequent in XLRS patients. Cone cell outer segment tips line defects and shortened PROS lengths as well as other photoreceptor microstructure defects may be closely related to poor vision in XLRS.

Cytologic appearance of retinal cells included in a fine-needle aspirate of a meningioma around the optic nerve of a dog.

PubMed

Tvedten, Harold; Hillström, Anna

2013-06-01

A 6-year-old Wirehair Dachshund had a meningioma around the optic nerve that caused exophthalmos. A benign mesenchymal tumor was suspected based on the cytologic pattern of a fine-needle aspirate, and a meningioma was diagnosed by histopathologic examination. In addition to the meningioma cells, the cytologic smears included groups of cells from apparently 4 layers of normal retina. In particular, uniform rod-shaped structures in the cytologic sample could suggest rod-shaped bacteria, but these structures were identified as cylindrical outer segments of photoreceptor rod cells. Other retinal structures recognized included pigmented epithelial layer cells with their uniquely formed pigment granules, the characteristic bi-lobed, cleaved nuclei from the outer nuclear layer, and nerve tissue likely from the outer plexiform layer of the retina. © 2013 American Society for Veterinary Clinical Pathology.

Macular retinal ganglion cell-inner plexiform layer thickness in patients on hydroxychloroquine therapy.

PubMed

Lee, Min Gyu; Kim, Sang Jin; Ham, Don-Il; Kang, Se Woong; Kee, Changwon; Lee, Jaejoon; Cha, Hoon-Suk; Koh, Eun-Mi

2014-11-25

We evaluated macular ganglion cell-inner plexiform layer (GC-IPL) thickness using spectral-domain optical coherence tomography (SD-OCT) in patients with chronic exposure to hydroxychloroquine (HCQ). This study included 130 subjects, who were divided into three groups: Group 1A, 55 patients with HCQ use ≥5 years; Group 1B, 46 patients with HCQ use <5 years; and Group 2, 29 normal controls. In all patients with exposure to HCQ, fundus examination, automated threshold perimetry, fundus autofluorescence photography, SD-OCT, and GC-IPL thickness measurement using the Cirrus HD-OCT ganglion cell analysis algorithm were performed. Average and minimum macular GC-IPL thickness were compared between subjects groups, and correlations between GC-IPL thickness and duration or total dose of HCQ use were analyzed. Among the 101 patients of Group 1, six patients who showed clinically evident HCQ retinopathy also showed markedly thin macular GC-IPL. In addition, weak but significant negative correlations were observed between the average and minimum GC-IPL thickness of Group 1 patients and cumulative dose of HCQ, even when analyzing without the six patients with HCQ retinopathy. However, when analyzing after exclusion of patients with high cumulative doses (>1000 g), significant correlations were not observed. This study revealed that macular GC-IPL thickness did not show definite correlations with HCQ use. However, some patients, especially with HCQ retinopathy or high cumulative doses, showed thin GC-IPL. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Modulation of Intersectin-1s Lung Expression Induces Obliterative Remodeling and Severe Plexiform Arteriopathy in the Murine Pulmonary Vascular Bed.

PubMed

Patel, Monal; Predescu, Dan; Bardita, Cristina; Chen, Jiwang; Jeganathan, Niranjan; Pritchard, Melanie; DiBartolo, Salvatore; Machado, Roberto; Predescu, Sanda

2017-03-01

Murine models of pulmonary arterial hypertension (PAH) that recapitulate the plexiform and obliterative arteriopathy seen in PAH patients and help in defining the molecular mechanisms involved are missing. Herein, we investigated whether intersectin-1s (ITSN) deficiency and prolonged lung expression of an ITSN fragment with endothelial cell (EC) proliferative potential (EH ITSN ), present in the lungs of PAH animal models and human patients, induce formation of plexiform/obliterative lesions and defined the molecular mechanisms involved. ITSN-deficient mice (knockout/heterozygous and knockdown) were subjected to targeted lung delivery of EH ITSN via liposomes for 20 days. Immunohistochemistry and histological and morphometric analyses revealed a twofold increase in proliferative ECs and a 1.35-fold increase in proliferative α-smooth muscle actin-positive cells in the lungs of ITSN-deficient mice, transduced with the EH ITSN relative to wild-type littermates. Treated mice developed severe medial wall hypertrophy, intima proliferation, and various forms of obliterative and plexiform-like lesions in pulmonary arteries, similar to PAH patients. Hemodynamic measurements indicated modest increases in the right ventricular systolic pressure and right ventricle hypertrophy. Transcriptional and protein assays of lung tissue indicated p38 MAPK -dependent activation of Elk-1 transcription factor and increased expression of c-Fos gene. This unique murine model of PAH-like plexiform/obliterative arteriopathy induced via a two-hit pathophysiological mechanism without hypoxia provides novel druggable targets to ameliorate and, perhaps, reverse the EC plexiform phenotype in severe human PAH. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Comparing the Rates of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Loss in Healthy Eyes and in Glaucoma Eyes.

PubMed

Hammel, Naama; Belghith, Akram; Weinreb, Robert N; Medeiros, Felipe A; Mendoza, Nadia; Zangwill, Linda M

2017-06-01

To compare the rates of circumpapillary retinal nerve fiber layer (RNFL) and macular retinal ganglion cell-inner plexiform layer (GCIPL) change over time in healthy and glaucoma eyes. Cohort study. The rates of circumpapillary RNFL and macular GCIPL loss in 28 healthy subjects and 97 glaucoma subjects from the Diagnostic Innovations in Glaucoma Study (DIGS) were compared using mixed-effects models. The median follow-up time and number of visits were 1.7 years and 6 visits and 3.2 years and 7 visits for healthy and glaucoma eyes, respectively. Significant rates of loss of both global circumpapillary RNFL and average macular GCIPL thickness were detectable in early and moderate glaucoma eyes; in severe glaucoma eyes, rates of average macular GCIPL loss were significant, but rates of global circumpapillary RNFL loss were not. In glaucoma eyes, mean rates of global circumpapillary RNFL thickness change (-0.98 μm/year [95% confidence interval (CI), -1.20 to -0.76]) and normalized global circumpapillary RNFL change (-1.7%/year [95% CI, -2.1 to -1.3]) were significantly faster than average macular GCIPL change (-0.57 μm/year [(95% CI, -0.73 to -0.41]) and normalized macular GCIPL change (-1.3%/year [95% CI, -1.7 to -0.9]). The rates of global and inferior RNFL change were weakly correlated with global and inferior macular GCIPL change (r ranges from 0.16 to 0.23, all P < .05). In this cohort, the rate of circumpapillary RNFL thickness change was faster than macular GCIPL change for glaucoma eyes. Global circumpapillary RNFL thickness loss was detectable in early and moderate glaucoma, and average macular GCIPL thickness loss was detectable in early, moderate, and severe glaucoma, suggesting that structural changes can be detected in severe glaucoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective Vulnerability of Specific Retinal Ganglion Cell Types and Synapses after Transient Ocular Hypertension.

PubMed

Ou, Yvonne; Jo, Rebecca E; Ullian, Erik M; Wong, Rachel O L; Della Santina, Luca

2016-08-31

Key issues concerning ganglion cell type-specific loss and synaptic changes in animal models of experimental glaucoma remain highly debated. Importantly, changes in the structure and function of various RGC types that occur early, within 14 d after acute, transient intraocular pressure elevation, have not been previously assessed. Using biolistic transfection of individual RGCs and multielectrode array recordings to measure light responses in mice, we examined the effects of laser-induced ocular hypertension on the structure and function of a subset of RGCs. Among the α-like RGCs studied, αOFF-transient RGCs exhibited higher rates of cell death, with corresponding reductions in dendritic area, dendritic complexity, and synapse density. Functionally, OFF-transient RGCs displayed decreases in spontaneous activity and receptive field size. In contrast, neither αOFF-sustained nor αON-sustained RGCs displayed decreases in light responses, although they did exhibit a decrease in excitatory postsynaptic sites, suggesting that synapse loss may be one of the earliest signs of degeneration. Interestingly, presynaptic ribbon density decreased to a greater degree in the OFF sublamina of the inner plexiform layer, corroborating the hypothesis that RGCs with dendrites stratifying in the OFF sublamina may be damaged early. Indeed, OFF arbors of ON-OFF RGCs lose complexity more rapidly than ON arbors. Our results reveal type-specific differences in RGC responses to injury with a selective vulnerability of αOFF-transient RGCs, and furthermore, an increased susceptibility of synapses in the OFF sublamina. The selective vulnerability of specific RGC types offers new avenues for the design of more sensitive functional tests and targeted neuroprotection. Conflicting reports regarding the selective vulnerability of specific retinal ganglion cell (RGC) types in glaucoma exist. We examine, for the first time, the effects of transient intraocular pressure elevation on the structure and function of various RGC types. Among the α-like RGCs studied, αOFF-transient RGCs are the most vulnerable to transient transient intraocular pressure elevation as measured by rates of cell death, morphologic alterations in dendrites and synapses, and physiological dysfunction. Specifically, we found that presynaptic ribbon density decreased to a greater degree in the OFF sublamina of the inner plexiform layer. Our results suggest selective vulnerability both of specific types of RGCs and of specific inner plexiform layer sublaminae, opening new avenues for identifying novel diagnostic and treatment targets in glaucoma. Copyright © 2016 the authors 0270-6474/16/369240-13$15.00/0.

[Persistence of the primordial vitreous body and buphthalmos].

PubMed

Cernea, P; Simionescu, C; Bosun, I

1995-01-01

Persistence of the hyperplasic primordial vitreous body is determined by a deletion of embryonal development of the vitreous body and of the hyaloid vascular system. Infant aged 3.5 years presents persistence of primordial vitreous body with crystalline dislocation in the camera aquosa and secondary buphthalmos of the left eye and microphthalmos with dislocation of the crystalline in the vitreous body of the right eye. At the back of the right eye we noticed a whitish mass, richly vascularized with vestiges from the hyaloid artery, but the posterior half of the vitreous cavity is filled with microscopic blood; the fibrovascular membrane is made of conjunctive tissue set in parallel layers and vessels with macrolipophagic degeneration. Microscopic investigation of retina reveals glial hyperplasia zones in the neighbourhood of the vitreous body. In the present paper the authors show the persistence of the primordial vitreous body in the left eye and bilateral dislocation of the crystalline, revealing multiple ocular malformations.

The effect of a hyperdynamic environment on the development of the rat retina

NASA Technical Reports Server (NTRS)

Murakami, D. M.; Fuller, C. A.

1985-01-01

The effects of a 2 G field on the retinal development of the layers in the rat and central visual system nuclei are investigated. The thickness of the retinal layers, ganglion cells, and brains of male and female Wistar rats suspended from an 18 foot diameter centrifuge creating a 2 G field are evaluated and compared with a control group. A decrease in the thickness of the outer nuclear layer (ONL) of 37.1 percent, of 58.5 percent in the inner nuclear layer (INL), and of 28.8 percent in the inner plexiform layer (IPL), and a reduction in body weight are observed in the 2-G rats. The data reveal that the ganglion cells and visual system nuclei activity correspond well with the control data; however, the medial terminal nucleus (MTN) activity is inhibited in the 2-G rats. It is concluded that the differences in ONL and IPL are attributed to body weight reduction, but the INL and MTN are affected by the 2-G conditions.

Eye lesions in pet birds.

PubMed

Tsai, S S; Park, J H; Hirai, K; Itakura, C

1993-03-01

Amongst eye lesions in birds that died in quarantine, cataracts were the most common disorders (37/241, 15.4%), being prevalent in the annular pads of cockatiels (Nymphicus hollandicus), Amazon parrots (Amazona aestiva aestiva) and budgerigars (Melopsittacus undulatus). The incidence in male birds was more than twice that in females. Deposition of crystals, mostly in the cornea, was the second most frequent lesion (21/293, 8.7%), mainly found in cockatiels, parakeets (Psittacula krameri manillensis), Amazon parrots (Amazona aestiva aestiva), budgerigars and finches (Poephila gouldiae gouldiae). These corneal crystals were negative to PAS and Kossa's stains. Six parakeets (Psittacula krameri manillensis) had calcium salts deposited in the inner plexiform layer of the retina and occasionally in the iris and ciliary body. Neither inflammation nor neo-vascularization was observed when cataracts, corneal crystalline deposition, and retinal and ciliary calcification were present. Intranuclear inclusion bodies typical for papovavirus infection were found in the eyelids of six budgerigars (2.5%). Similar inclusions were simultaneously found in the pars ciliaris retinae (4, 1.7%), inner plexiform of retina (1, 0.4%) and anterior epithelium of the cornea (1, 0.4%). Other lesions such as candidial endophthalmitis, conjunctival cryptosporidiosis, corneal dystrophy, keratitis, corneal perforation and iridocyclitis, were occasional findings.

Automated classifiers for early detection and diagnosis of retinopathy in diabetic eyes.

PubMed

Somfai, Gábor Márk; Tátrai, Erika; Laurik, Lenke; Varga, Boglárka; Ölvedy, Veronika; Jiang, Hong; Wang, Jianhua; Smiddy, William E; Somogyi, Anikó; DeBuc, Delia Cabrera

2014-04-12

Artificial neural networks (ANNs) have been used to classify eye diseases, such as diabetic retinopathy (DR) and glaucoma. DR is the leading cause of blindness in working-age adults in the developed world. The implementation of DR diagnostic routines could be feasibly improved by the integration of structural and optical property test measurements of the retinal structure that provide important and complementary information for reaching a diagnosis. In this study, we evaluate the capability of several structural and optical features (thickness, total reflectance and fractal dimension) of various intraretinal layers extracted from optical coherence tomography images to train a Bayesian ANN to discriminate between healthy and diabetic eyes with and with no mild retinopathy. When exploring the probability as to whether the subject's eye was healthy (diagnostic condition, Test 1), we found that the structural and optical property features of the outer plexiform layer (OPL) and the complex formed by the ganglion cell and inner plexiform layers (GCL + IPL) provided the highest probability (positive predictive value (PPV) of 91% and 89%, respectively) for the proportion of patients with positive test results (healthy condition) who were correctly diagnosed (Test 1). The true negative, TP and PPV values remained stable despite the different sizes of training data sets (Test 2). The sensitivity, specificity and PPV were greater or close to 0.70 for the retinal nerve fiber layer's features, photoreceptor outer segments and retinal pigment epithelium when 23 diabetic eyes with mild retinopathy were mixed with 38 diabetic eyes with no retinopathy (Test 3). A Bayesian ANN trained on structural and optical features from optical coherence tomography data can successfully discriminate between healthy and diabetic eyes with and with no retinopathy. The fractal dimension of the OPL and the GCL + IPL complex predicted by the Bayesian radial basis function network provides better diagnostic utility to classify diabetic eyes with mild retinopathy. Moreover, the thickness and fractal dimension parameters of the retinal nerve fiber layer, photoreceptor outer segments and retinal pigment epithelium show promise for the diagnostic classification between diabetic eyes with and with no mild retinopathy.

High-Resolution Imaging of the Optic Nerve and Retina in Optic Nerve Hypoplasia

PubMed Central

Pilat, Anastasia; Sibley, Daniel; McLean, Rebecca J.; Proudlock, Frank A.; Gottlob, Irene

2015-01-01

Purpose To investigate the optic nerve and macular morphology in patients with optic nerve hypoplasia (ONH) using spectral-domain optical coherence tomography (SD OCT). Design Prospective, cross-sectional, observational study. Subjects A total of 16 participants with ONH (10 female and 6 male; mean age, 17.2 years; 6 bilateral involvement) and 32 gender-, age-, ethnicity-, and refraction-matched healthy controls. Methods High-resolution SD OCT (Copernicus [Optopol Technology S.A., Zawiercie, Poland], 3 μm resolution) and handheld SD OCT (Bioptigen Inc [Research Triangle Park, NC], 2.6 μm resolution) devices were used to acquire horizontal scans through the center of the optic disc and macula. Main Outcome Measures Horizontal optic disc/cup and rim diameters, cup depth, peripapillary retinal nerve fiber layer (RNFL), and thickness of individual retinal layers in participants with ONH and in controls. Results Patients with ONH had significantly smaller discs (P < 0.03 and P < 0.001 compared with unaffected eye and healthy controls, respectively), horizontal cup diameter (P < 0.02 for both), and cup depth (P < 0.02 and P < 0.01, respectively). In the macula, significantly thinner RNFL (nasally), ganglion cell layer (GCL) (nasally and temporally), inner plexiform layer (IPL) (nasally), outer nuclear layer (ONL) (nasally), and inner segment (centrally and temporally) were found in patients with ONH compared with the control group (P < 0.05 for all comparisons). Continuation of significantly thicker GCL, IPL, and outer plexiform layer in the central retinal area (i.e., foveal hypoplasia) was found in more than 80% of patients with ONH. Clinically unaffected fellow eyes of patients with ONH showed mild features of underdevelopment. Visual acuity and presence of septo-optic dysplasia were associated with changes in GCL and IPL. Sensitivity and specificity for the detection of ONH based on disc and retinal optical coherence tomography (OCT) parameters were >80%. Conclusions Our study provides evidence of retinal changes in ONH. In addition to thinning of retina layers mainly involving the RNFL and GCL, signs reminiscent of foveal hypoplasia were observed in patients with ONH. Optic nerve and foveal parameters measured using OCT showed high sensitivity and specificity for detecting ONH, demonstrating their useful for clinical diagnosis. PMID:25939636

Three-dimensional spectral domain optical coherence tomography in X linked foveal retinoschisis

PubMed Central

Saxena, Sandeep; Manisha; Meyer, Carsten H

2013-01-01

Spectral domain optical coherence tomography (SD-OCT) was performed in two cases of bilateral X linked foveal retinoschisis of different age groups. On fundus examination spoke wheel and honeycomb pattern of cysts were observed along with retinal nerve fibre layer (RNFL) defects. On SD-OCT, schisis was observed in the outer plexiform layer. External limiting membrane disruption was observed in the subfoveal area, along with disruption of outer nuclear layer (ONL) and inner–outer segment junction. Elevation of ONL due to tractional pull of central palisade was a novel observation. Retinoschisis extended beyond the optic disc up to the nasal region. Extracted RNFL tomogram presented an unprecedented visualisation of schisis along 360° of the optic disc. Tractional elevation in the foveal area and schisis involving nasal region, not observed upon clinical examination, was highlighted on SD-OCT. This investigative modality is an important adjunct in the assessment of foveal retinoschisis. PMID:23563673

Cholinesterases and cell proliferation in "nonstratified" and "stratified" cell aggregates from chicken retina and tectum.

PubMed

Vollmer, G; Layer, P G

1987-12-01

Dissociated single cells from chicken retina or tectum kept in rotation-mediated cell culture aggregate, proliferate and establish a certain degree of histotypical cell-to-cell relationships ("sorting out"), but these systems never form highly laminated aggregates ("nonstratified" R- and T-aggregates). In contrast, a mixture of retinal plus pigment epithelial cells forms highly "stratified" aggregates ("RPE-aggregates", see Vollmer et al. 1984). The present comparative study of "stratified" and "nonstratified" aggregates enables us to investigate the process of cell proliferation uncoupled from that of tissue stratification. Here we try to relate these two basic neurogenetic processes with patterns of expression of cholinesterases (AChE, BChE) during formation of both types of aggregates. During early aggregate formation, in both "stratified" and "nonstratified" aggregates an increased butyrylcholinesterase activity is observed close to mitotically active cells. Quantitatively both phenomena show their maxima after 2-3 days in culture. In contrast, AChE-expression in all systems increases with incubation time. In nonproliferative areas, in the center of RPE-aggregates, the formation of plexiform layers is characterized initially by weak BChE- and then strong AChE-activity. These areas correspond with the inner (IPL) and outer (OPL) plexiform layers of the retina in vivo. Although by sucrose gradient centrifugation we find that the 6S- and the fiber-associated 11S-molecules of AChE are present in all types of aggregates, during the culture period the ratio of 11S/6S-forms increases only in RPE-aggregates, which again indicates the advanced degree of differentiation within these aggregates.(ABSTRACT TRUNCATED AT 250 WORDS)

Glaucoma-Diagnostic Ability of Ganglion Cell-Inner Plexiform Layer Thickness Difference Across Temporal Raphe in Highly Myopic Eyes.

PubMed

Kim, Young Kook; Yoo, Byeong Wook; Jeoung, Jin Wook; Kim, Hee Chan; Kim, Hae Jin; Park, Ki Ho

2016-11-01

To evaluate the glaucoma-diagnostic ability of the ganglion cell-inner plexiform layer (GCIPL) thickness difference across the temporal raphe in highly myopic eyes. We consecutively enrolled a total of 195 highly myopic eyes (axial length [AL] >26.5 mm) of 195 subjects: 93 glaucoma patients along with and 102 nonglaucomatous subjects. Cirrus high-definition optical coherence tomography (OCT) was employed to scan all of the subjects' macular and optic discs. Using a MATLAB-based customized program (the GCIPL hemifield test), a positive test result was automatically declared if the following two conditions were met: (1) the horizontal line is detected for longer than one-half of the distance from the temporal inner elliptical annulus to the outer elliptical annulus, and (2) the average GCIPL thickness difference within 10 pixels of the reference line, both above and below, is 5 μm or more. The glaucoma-diagnostic ability was computed using the area under the receiver operating characteristic curve (AUC). Among the glaucomatous eyes, GCIPL hemifield test positivity was shown in 92.5% (86 of 93), significantly higher than that for the nonglaucomatous eyes (4.90%, 5 of 102; P <0.001). The value of AUC for the GCIPL hemifield test was excellent (0.938; sensitivity 92.50%, specificity 95.10%) and was the best compared with those for any of OCT parameters. In highly myopic eyes, determination of the presence or absence of GCIPL thickness difference across the temporal raphe via OCT macula scan can be a useful means of distinguishing the glaucomatous damage.

Dendrodendritic Synapses in the Mouse Olfactory Bulb External Plexiform Layer

PubMed Central

Bartel, Dianna L.; Rela, Lorena; Hsieh, Lawrence; Greer, Charles A.

2014-01-01

Odor information relayed by olfactory bulb projection neurons, mitral and tufted cells (M/T), is modulated by pairs of reciprocal dendrodendritic synaptic circuits in the external plexiform layer (EPL). Interneurons, which are accounted for largely by granule cells, receive depolarizing input from M/T dendrites and in turn inhibit current spread in M/T dendrites via hyperpolarizing reciprocal dendrodendritic synapses. Because the location of dendrodendritic synapses may significantly affect the cascade of odor information, we assessed synaptic properties and density within sublaminae of the EPL and along the length of M/T secondary dendrites. In electron micrographs the M/T to granule cell synapse appeared to predominate and were equivalent in both the outer and inner EPL. However, the dendrodendritic synapses from granule cell spines onto M/T dendrites, were more prevalent in the outer EPL. In contrast, individual gephyrin-IR puncta, a postsynaptic scaffolding protein at inhibitory synapses used here as a proxy for the granule to M/T dendritic synapse was equally distributed throughout the EPL. Of significance to the organization of intrabulbar circuits, gephyrin-IR synapses are not uniformly distributed along M/T secondary dendrites. Synaptic density, expressed as a function of surface area, increases distal to the cell body. Furthermore, the distributions of gephyrin-IR puncta are heterogeneous and appear as clusters along the length of the M/T dendrites. Consistent with computational models, our data suggest that temporal coding in M/T cells is achieved by precisely located inhibitory input and that distance from the soma is compensated with an increase in synaptic density. PMID:25420934

DSCAM Localization and Function at the Mouse Cone Synapse

PubMed Central

de Andrade, Gabriel Belem; Long, Samuel S.; Fleming, Harrison; Li, Wei; Fuerst, Peter G.

2014-01-01

The Down Syndrome Cell Adhesion Molecule (DSCAM) is required for regulation of cell number, soma spacing and cell type specific dendrite avoidance in many types of retinal ganglion and amacrine cells. In this study we assay the organization of cells making up the outer plexiform layer of the retina in the absence of Dscam. Some types of OFF bipolar cells, type 3b and type 4 bipolar cells, had defects in dendrite arborization in the Dscam mutant retina, while other cell types appeared similar to wild type. The cone synapses that these cells project their dendrites to were intact, as visualized by electron microscopy, and had a distribution and density that was not significantly different than wild type. The spacing of type 3b bipolar cell dendrites was further analyzed by Voronoi domain analysis, Density Recovery Profiling (DRP) analysis and Nearest Neighbor Analysis (NNA). Spacing was found to be significantly different when comparing wild type and mutant type 3b bipolar cell dendrites. Defects in arborization of these bipolar cells could not be attributed to the disorganization of inner plexiform layer cells that occurs in the Dscam mutant retina or an increase in cell number, as they arborized when Dscam was targeted in retinal ganglion cells only or in the bax null retina. Localization of DSCAM was assayed and the protein was localized near to cone synapses in mouse, macaque and ground squirrel retinas. DSCAM protein was detected in several types of bipolar cells, including type 3b and type 4 bipolar cells. PMID:24477985

An animal model for Norrie disease (ND): gene targeting of the mouse ND gene.

PubMed

Berger, W; van de Pol, D; Bächner, D; Oerlemans, F; Winkens, H; Hameister, H; Wieringa, B; Hendriks, W; Ropers, H H

1996-01-01

In order to elucidate the cellular and molecular processes which are involved in Norrie disease (ND), we have used gene targeting technology to generate ND mutant mice. The murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with its human counterpart. RNA in situ hybridization revealed expression in retina, brain and the olfactory bulb and epithelium of 2 week old mice. Hemizygous mice carrying a replacement mutation in exon 2 of the ND gene developed retrolental structures in the vitreous body and showed an overall disorganization of the retinal ganglion cell layer. The outer plexiform layer disappears occasionally, resulting in a juxtaposed inner and outer nuclear layer. At the same regions, the outer segments of the photoreceptor cell layer are no longer present. These ocular findings are consistent with observations in ND patients and the generated mouse line provides a faithful model for study of early pathogenic events in this severe X-linked recessive neurological disorder.

Duodenal plexiform fibromyxoma as a cause of obscure upper gastrointestinal bleeding: A case report.

PubMed

Moris, Demetrios; Spanou, Evangelia; Sougioultzis, Stavros; Dimitrokallis, Nikolaos; Kalisperati, Polyxeni; Delladetsima, Ioanna; Felekouras, Evangelos

2017-01-01

We are reporting the first-to our knowledge-case of duodenal Plexiform Fibromyxoma causing obscure upper gastrointestinal bleeding. Plexiform fibromyxoma triggered recurrent upper gastrointestinal bleeding episodes in a 63-year-old man who remained undiagnosed, despite multiple hospitalizations, extensive diagnostic workups and surgical interventions (including gastrectomies), for almost 17 years. During hospitalization for the last bleeding episode, an upper gastrointestinal endoscopy revealed an intestinal hemorrhagic nodule. The lesion was deemed unresectable by endoscopic means. An abdominal computerized tomography disclosed no further lesions and surgery was decided. The lesion at operation was found near the edge of the duodenal stump and treated with pancreas-preserving duodenectomy (1st and 2nd portion). Postoperative recovery was mainly uneventful and a 20-month follow-up finds the patient in good health with no need for blood transfusions.Plexiform fibromyxomas stand for a rare and widely unknown mesenchymal entity. Despite the fact that they closely resemble other gastrointestinal tumors, they distinctly vary in clinical management as well as the histopathology. Clinical awareness and further research are compulsory to elucidate its clinical course and prognosis.

Patterns and Rates of Supplementary Venous Drainage to the Internal Jugular Veins.

PubMed

Qureshi, Adnan I; Ishfaq, Muhammad Fawad; Herial, Nabeel A; Khan, Asif A; Suri, M Fareed K

2016-07-01

Several studies have found supplemental venous drainage channels in addition to bilateral internal jugular veins for cerebral venous efflux. We performed this study to characterize the supplemental venous outflow patterns in a consecutive series of patients undergoing detailed cerebral angiography with venous phase imaging. The venographic phase of the arteriogram was reviewed to identify and classify supplemental cerebral venous drainage into anterior (cavernous venous sinus draining into pterygoid plexus and retromandibular vein) and posterior drainage pattern. The posterior drainage pattern was further divided into plexiform pattern (with sigmoid venous sinus draining into the paravertebral venous plexus), and solitary vein pattern (dominant single draining deep cervical vein) drainage. The posterior plexiform pattern was further divided into 2 groups: posterior plexiform with or without prominent solitary vein. Supplemental venous drainage was seen ipsilateral to internal jugular vein in 76 (43.7%) of 174 venous drainages (87 patients) analyzed. The patterns were anterior (n = 23, 13.2%), posterior plexiform without prominent solitary vein (n = 40, 23%), posterior plexiform with prominent solitary vein (n = 62, 35.6%), and posterior solitary vein alone (n = 3, 1.7%); occipital emissary veins and/or transosseous veins were seen in 1 supplemental venous drainage. Concurrent ipsilateral anterior and posterior supplemental drainage was seen in 6 of 174 venous drainages analyzed. We provide an assessment of patterns and rates of supplementary venous drainage to internal jugular veins to improve our understanding of anatomical and physiological aspects of cerebral venous drainage. Copyright © 2016 by the American Society of Neuroimaging.

Diagnostic performance of optical coherence tomography ganglion cell--inner plexiform layer thickness measurements in early glaucoma.

PubMed

Mwanza, Jean-Claude; Budenz, Donald L; Godfrey, David G; Neelakantan, Arvind; Sayyad, Fouad E; Chang, Robert T; Lee, Richard K

2014-04-01

To evaluate the glaucoma diagnostic performance of ganglion cell inner-plexiform layer (GCIPL) parameters used individually and in combination with retinal nerve fiber layer (RNFL) or optic nerve head (ONH) parameters measured with Cirrus HD-OCT (Carl Zeiss Meditec, Inc, Dublin, CA). Prospective cross-sectional study. Fifty patients with early perimetric glaucoma and 49 age-matched healthy subjects. Three peripapillary RNFL and 3 macular GCIPL scans were obtained in 1 eye of each participant. A patient was considered glaucomatous if at least 2 of the 3 RNFL or GCIPL scans had the average or at least 1 sector measurement flagged at 1% to 5% or less than 1%. The diagnostic performance was determined for each GCIPL, RNFL, and ONH parameter as well as for binary or-logic and and-logic combinations of GCIPL with RNFL or ONH parameters. Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Among GCIPL parameters, the minimum had the best diagnostic performance (sensitivity, 82.0%; specificity, 87.8%; PLR, 6.69; and NLR, 0.21). Inferior quadrant was the best RNFL parameter (sensitivity, 74%; specificity, 95.9%; PLR, 18.13; and NLR, 0.27), as was rim area (sensitivity, 68%; specificity, 98%; PLR, 33.3; and NLR, 0.33) among ONH parameters. The or-logic combination of minimum GCIPL and average RNFL provided the overall best diagnostic performance (sensitivity, 94%; specificity, 85.7%; PRL, 6.58; and NLR, 0.07) as compared with the best RNFL, best ONH, and best and-logic combination (minimum GCIPL and inferior quadrant RNFL; sensitivity, 64%; specificity, 100%; PLR, infinity; and NPR, 0.36). The binary or-logic combination of minimum GCIPL and average RNFL or rim area provides better diagnostic performances than those of and-logic combinations or best single GCIPL, RNFL, or ONH parameters. This finding may be clinically valuable for the diagnosis of early glaucoma. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Relation Between Macular Retinal Ganglion Cell/Inner Plexiform Layer Thickness and Multifocal Electroretinogram Measures in Experimental Glaucoma

PubMed Central

Luo, Xunda; Patel, Nimesh B.; Rajagopalan, Lakshmi P.; Harwerth, Ronald S.; Frishman, Laura J.

2014-01-01

Purpose. We investigated relations between macular retinal ganglion cell plus inner plexiform layer (RGC+IPL) thickness and macular retinal function revealed by multifocal electroretinonography (mfERG) in a nonhuman primate model of experimental glaucoma. Methods. Retinal ganglion cell (RGC) structure and function were followed with spectral-domain optical coherence tomography (SD-OCT) and ERGs in five macaques with unilateral experimental glaucoma. Linear regression was used to study correlations in control (Con) and experimental (Exp) eyes between peripapillary retinal nerve fiber layer (RNFL) thickness, macular RGC+IPL thickness, multifocal photopic negative response (mfPhNR) and high-frequency multifocal oscillatory potentials (mfOP) in slow-sequence mfERG, and low-frequency component (mfLFC) in global-flash mfERG. We used ANOVA and paired t-tests to compare glaucoma-related mfERG changes between superior and inferior hemifields, foveal hexagon, inner three rings, and four quadrants of macula. Results. Average macular RGC+IPL and temporal RNFL thickness were strongly correlated (r2 = 0.90, P < 0.001). In hexagon-by-hexagon analysis, all three mfERG measures were correlated (P < 0.001) with RGC+IPL thickness for Con (r2, 0.33–0.51) and Exp eyes (r2, 0.17–0.35). The RGC structural and functional metrics decreased as eccentricity increased. The reduction in amplitude of mfERG measures in Exp eyes relative to Con eyes was proportionally greater, in general, than the relative thinning of RGC+IPL at the same location for eyes in which structural loss was not evident, or mild to moderate. Although not statistically significant, percent amplitude reduction of mfERG measures was greatest in the inferior temporal quadrant. Conclusions. Macular RGC+IPL thickness and mfERG measures of RGC function can be complementary tools in assessing glaucomatous neuropathy. PMID:24970256

Ganglion cell-inner plexiform layer and retinal nerve fiber layer thickness according to myopia and optic disc area: a quantitative and three-dimensional analysis.

PubMed

Seo, Sam; Lee, Chong Eun; Jeong, Jae Hoon; Park, Ki Ho; Kim, Dong Myung; Jeoung, Jin Wook

2017-03-11

To determine the influences of myopia and optic disc size on ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) thickness profiles obtained by spectral domain optical coherence tomography (OCT). One hundred and sixty-eight eyes of 168 young myopic subjects were recruited and assigned to one of three groups according to their spherical equivalent (SE) values and optic disc area. All underwent Cirrus HD-OCT imaging. The influences of myopia and optic disc size on the GCIPL and RNFL thickness profiles were evaluated by multiple comparisons and linear regression analysis. Three-dimensional surface plots of GCIPL and RNFL thickness corresponding to different combinations of myopia and optic disc size were constructed. Each of the quadrant RNFL thicknesses and their overall average were significantly thinner in high myopia compared to low myopia, except for the temporal quadrant (all Ps ≤0.003). The average and all-sectors GCIPL were significantly thinner in high myopia than in moderate- and/or low-myopia (all Ps ≤0.002). The average OCT RNFL thickness was correlated significantly with SE (0.81 μm/diopter, P < 0.001), axial length (-1.44 μm/mm, P < 0.001), and optic disc area (5.35 μm/mm 2 , P < 0.001) by linear regression analysis. As for the OCT GCIPL parameters, average GCIPL thickness showed a significant correlation with SE (0.84 μm/diopter, P < 0.001) and axial length (-1.65 μm/mm, P < 0.001). There was no significant correlation of average GCIPL thickness with optic disc area. Three-dimensional curves showed that larger optic discs were associated with increased average RNFL thickness and that more-myopic eyes were associated with decreased average GCIPL and RNFL thickness. Myopia can significantly affect GCIPL and RNFL thickness profiles, and optic disc size has a significant influence on RNFL thickness. The current OCT maps employed in the evaluation of glaucoma should be analyzed in consideration of refractive status and optic disc size.

Expression of nitric oxide synthase during the development of RCS rat retinas.

PubMed

Sharma, R K; Warfvinge, K; Ehinger, B

2001-01-01

Nitric oxide (NO) has been reported to be both neurodestructive and neuroprotective in the central nervous system and could possibly play an important role in neurodegenerative disorders. On the assumption that NO synthesis may influence degenerative processes in the retina, we have examined the development and distribution of nitric-oxide-synthase(NOS)-immunoreactive cells in developing Royal College of Surgeons (RCS) rat retinas, which is an animal model for retinal degeneration. An antibody against constitutive neuronal NOS was used for immunocytochemistry on RCS rat retinas from postnatal (PN) days 3, 7, 10, 14, 35, 70 and 281 and compared with that in the normal rats of PN days 3, 7, 10, 14, 54 and adults. Immunoreactive cells were not seen in PN 3 retinas but were distinctly seen in the PN 7 retina along with a plexus in the inner plexiform layer. In both groups (normal and RCS rats) a distinct sublayering of the plexus in the inner plexiform layer could be seen at PN 10, which became more distinct at PN 14. The immunoreactive cells were detected also in the oldest retina examined, which was PN 281 in the case of RCS rats. In both groups, certain amacrine cells, certain bipolar cells and certain horizontal cells were found to be immunoreactive. In conclusion, the developmental timetable of the NOS immunoreactivity was identical in the normal and the RCS rat retinas. The NOS-immunoreactive cells persisted in the RCS retinas even when the retina had degenerated extensively. Abnormalities with the inducible isoforms of NOS cannot be ruled out from this study. We conclude that the chronological and qualitative development of the constitutive neuronal NOS immunoreactivity is normal in RCS rat retinas. Copyright 2001 S. Karger AG, Basel

Evidence that ganglion cells react to retinal detachment.

PubMed

Coblentz, Francie E; Radeke, Monte J; Lewis, Geoffrey P; Fisher, Steven K

2003-03-01

Growth associated protein 43 (GAP 43) is involved in synapse formation and it is expressed in the retina in a very specific pattern. Although GAP 43 is downregulated at the time of synapse formation, it can be re-expressed following injury such as axotomy or ischemia. Because of this we sought to characterize the expression of GAP 43 after retinal detachment (RD). Immunoblot, immunocytochemical and quantitative polymerase chain reaction (QPCR) techniques were used to assess the level of GAP 43 expression after experimental RD. GAP 43 was localized to three sublaminae of the inner plexiform layer of the normal retina. GAP 43 became upregulated in a subset of retinal ganglion cells following at least 7 days of RD. By immunoblot GAP 43 could be detected by 3 days. QPCR shows the upregulation of GAP 43 message by 6hr of detachment. To further characterize changes in ganglion cells, we used an antibody to neurofilament 70 and 200kDa (NF) proteins. Anti-NF labels horizontal cells, ganglion cell dendrites in the inner plexiform layer, and ganglion cell axons (fasicles) in the normal retina. Following detachment it is upregulated in horizontal cells and ganglion cells. When detached retina was double labelled with anti-GAP 43 and anti-NF, some cells were labelled with both markers, while others labelled with only one. We have previously shown that second order neurons respond to detachment; here we show that third order neurons are responding as well. Cellular remodelling of this type in response to detachment may explain the slow recovery of vision that often occurs after reattachment, or those changes that are often assumed to be permanent.

Electrophysiological mapping of the accessory olfactory bulb of the rabbit (Oryctolagus cuniculus).

PubMed

van Groen, T; Ruardy, L; da Silva, F H

1986-07-01

Field potentials elicited by electrical stimulation of the vomeronasal nerve were measured in the accessory olfactory bulb of the rabbit. Maps were made of the distribution of surface field potentials and of the corresponding depth profiles. The surface maps followed closely the contours of the accessory olfactory bulb: at the frontal border the field potential tended to zero and at the center of the structure the field potential attained a maximum. Depth profiles of the field potentials through the accessory olfactory bulb presented a surface-negative wave and, in depth, a positive wave. The polarity reversal occurred at the deep part of the granule cell layer. The zero equipotential line followed closely the curvature of the granule cell layer. Current source density analysis of the depth profiles revealed a main sink at the external plexiform and granule cell layers. This indicates that the main activity in the accessory olfactory bulb is generated by the synapses between the mitral cells and the granule cells as is found in the main olfactory bulb.

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath Tumors and Plexiform Neurofibromas

DTIC Science & Technology

2011-09-01

with an accelerated schedule Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform Neurofibromas (PN...the distribution of macromolecules delivered to intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural NF1...determine the efficacy CED of the epidermal growth factor receptor (EGFR) inhibitor erlotinib in animal models of intraneural PNs and MPNST

Primordial clays on Mars formed beneath a steam or supercritical atmosphere.

PubMed

Cannon, Kevin M; Parman, Stephen W; Mustard, John F

2017-12-06

On Mars, clay minerals are widespread in terrains that date back to the Noachian period (4.1 billion to 3.7 billion years ago). It is thought that the Martian basaltic crust reacted with liquid water during this time to form hydrated clay minerals. Here we propose, however, that a substantial proportion of these clays was formed when Mars' primary crust reacted with a dense steam or supercritical atmosphere of water and carbon dioxide that was outgassed during magma ocean cooling. We present experimental evidence that shows rapid clay formation under conditions that would have been present at the base of such an atmosphere and also deeper in the porous crust. Furthermore, we explore the fate of a primordial clay-rich layer with the help of a parameterized crustal evolution model; we find that the primordial clay is locally disrupted by impacts and buried by impact-ejected material and by erupted volcanic material, but that it survives as a mostly coherent layer at depth, with limited surface exposures. These exposures are similar to those observed in remotely sensed orbital data from Mars. Our results can explain the present distribution of many clays on Mars, and the anomalously low density of the Martian crust in comparison with expectations.

Primordial clays on Mars formed beneath a steam or supercritical atmosphere

NASA Astrophysics Data System (ADS)

Cannon, Kevin M.; Parman, Stephen W.; Mustard, John F.

2017-12-01

On Mars, clay minerals are widespread in terrains that date back to the Noachian period (4.1 billion to 3.7 billion years ago). It is thought that the Martian basaltic crust reacted with liquid water during this time to form hydrated clay minerals. Here we propose, however, that a substantial proportion of these clays was formed when Mars’ primary crust reacted with a dense steam or supercritical atmosphere of water and carbon dioxide that was outgassed during magma ocean cooling. We present experimental evidence that shows rapid clay formation under conditions that would have been present at the base of such an atmosphere and also deeper in the porous crust. Furthermore, we explore the fate of a primordial clay-rich layer with the help of a parameterized crustal evolution model; we find that the primordial clay is locally disrupted by impacts and buried by impact-ejected material and by erupted volcanic material, but that it survives as a mostly coherent layer at depth, with limited surface exposures. These exposures are similar to those observed in remotely sensed orbital data from Mars. Our results can explain the present distribution of many clays on Mars, and the anomalously low density of the Martian crust in comparison with expectations.

Neurofibromatosis type 1 with external genitalia involvement presentation of 4 patients.

PubMed

Pascual-Castroviejo, Ignacio; Lopez-Pereira, Pedro; Savasta, Salvatore; Lopez-Gutierrez, Juan Carlos; Lago, Carlos Míguelez; Cisternino, Mariangela

2008-11-01

Genitourinary neurofibromas with clitoral involvement in neurofibromatosis type 1 are rare, and even more infrequent are the neurofibromas involving genitalia in males. The most frequent presenting sign of neurofibroma in females is clitoromegaly with pseudopenis, and enlarged penis is the most common sign in males. Labium majus neurofibroma not associated with clitoral involvement is extremely rare. Magnetic resonance imaging demonstration of the neurofibromas has seldom been reported. We report 4 children, 3 girls and 1 boy, with plexiform neurofibromas involving the external genitalia. Three of the 4 patients had histologic confirmation of neurofibroma. Two girls with clitoral hypertrophy had a neurofibroma that infiltrated the clitoris and extended unilaterally to the lower bladder wall. One girl had a plexiform neurofibroma that affected a labium. One boy with asymmetric penile hypertrophy since 2 years of age and ipsilateral gluteal hypertrophy had plexiform neurofibromas that extended between the left lumbogluteal and penile regions, infiltrating the left rectum wall and bladder with compression of both structures, the left prostate, and the left half of the cavernous corpi with hypertrophy of this part and asymmetry of the penis. Magnetic resonance imaging demonstrated in all patients that external genitalia and plexiform neurofibroma formed images of nondetachable structures. However, hermaphroditism was discarded by chromosomal study in all 3 girls before ratifying the diagnosis of external genitalia neurofibroma.

Ganglion cell loss in relation to visual disability in multiple sclerosis.

PubMed

Walter, Scott D; Ishikawa, Hiroshi; Galetta, Kristin M; Sakai, Reiko E; Feller, Daniel J; Henderson, Sam B; Wilson, James A; Maguire, Maureen G; Galetta, Steven L; Frohman, Elliot; Calabresi, Peter A; Schuman, Joel S; Balcer, Laura J

2012-06-01

We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS). Cross-sectional study. A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment. The SD-OCT images were captured using Macular Cube (200×200 or 512×128) and ONH Cube 200×200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined. The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score. Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (P<0.001 and P = 0.001) and in MS ON versus non-ON eyes (P<0.001 for both measures). Peripapillary RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were significantly correlated with VA (P≤0.001), 2.5% LCLA (P<0.001), and 1.25% LCLA (P≤0.001). Among OCT measurements, reductions in GCL+IPL (P<0.001), macular RNFL (P = 0.006), and the combination (macular RNFL+GCL+IPL; P<0.001) were most strongly associated with lower (worse) NEI-VFQ-25 and 10-Item Supplement QOL scores; GCL+IPL thinning was significant even accounting for macular RNFL thickness (P = 0.03 for GCL+IPL, P = 0.39 for macular RNFL). We demonstrated that GCL+IPL thinning is most significantly correlated with both visual function and vision-specific QOL in MS, and may serve as a useful structural marker of disease. Our findings parallel those of magnetic resonance imaging studies that show gray matter disease is a marker of neurologic disability in MS. Proprietary or commercial disclosure may be found after the references. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Biomedical Applications of Mid-Infrared Spectroscopic Imaging and Multivariate Data Analysis: Contribution to the Understanding of Diabetes Pathogenesis

NASA Astrophysics Data System (ADS)

Aboualizadeh, Ebrahim

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of adult vision loss. Although a great deal of progress has been made in ophthalmological examinations and clinical approaches to detect the signs of retinopathy in patients with diabetes, there still remain outstanding questions regarding the molecular and biochemical changes involved. To discover the biochemical mechanisms underlying the development and progression of changes in the retina as a result of diabetes, a more comprehensive understanding of the bio-molecular processes, in individual retinal cells subjected to hyperglycemia, is required. Animal models provide a suitable resource for temporal detection of the underlying pathophysiological and biochemical changes associated with DR, which is not fully attainable in human studies. In the present study, I aimed to determine the nature of diabetes-induced, highly localized biochemical changes in the retinal tissue from Ins2Akita/+ (Akita/+; a model of Type I diabetes) male mice with different duration of diabetes. Employing label-free, spatially resolved Fourier transform infrared (FT-IR) imaging engaged with chemometric tools enabled me to identify temporal-dependent reproducible biomarkers of the diabetic retinal tissue from mice with 6 or 12 weeks, and 6 or 10 months of diabetes. I report, for the first time, the origin of molecular changes in the biochemistry of individual retinal layers with different duration of diabetes. A robust classification between distinctive retinal layers - namely photoreceptor layer (PRL), outer plexiform layer (OPL), inner nuclear layer (INL), and inner plexiform layer (IPL) - and associated temporal-dependent spectral biomarkers, were delineated. Spatially-resolved super resolution chemical images revealed oxidative stress-induced structural and morphological alterations within the nucleus of the photoreceptors. Comparison among the PRL, OPL, INL, and IPL suggested that the photoreceptor layer is the most susceptible layer to the oxidative stress with short-duration of diabetes. Moreover, for the first time, we present the temporal-dependent molecular alterations for the PRL, OPL, INL, and IPL from Akita/+ mice, with progression of diabetes. These findings are potentially important and may be of particular benefit in understanding the molecular and biological activity of retinal cells during oxidative stress in diabetes. Our integrating paradigm provides a new conceptual framework and a significant rationale for a better understanding of the molecular and cellular mechanisms underlying the development and progression of DR. This approach may yield alternative and potentially complimentary methods for the assessment of diabetes changes. It is expected that the conclusions drawn from this work will bridge the gap in our knowledge regarding the biochemical mechanisms of the DR and address some critical needs in the biomedical community.

A potential reservoir of immature dopaminergic replacement neurons in the adult mammalian olfactory bulb.

PubMed

Pignatelli, Angela; Ackman, James B; Vigetti, Davide; Beltrami, Antonio P; Zucchini, Silvia; Belluzzi, Ottorino

2009-02-01

A significant fraction of the interneurons added in adulthood to the glomerular layer (GL) of the olfactory bulb (OB) are dopaminergic (DA). In the OB, DA neurons are restricted to the GL, but using transgenic mice expressing eGFP under the tyrosine hydroxylase (TH) promoter, we also detected the presence of TH-GFP+ cells in the mitral and external plexiform layers. We hypothesized that these could be adult-generated neurons committed to become DA but not yet entirely differentiated. Accordingly, TH-GFP+ cells outside the GL exhibit functional properties (appearance of pacemaker currents, synaptic connection with the olfactory nerve, intracellular chloride concentration, and other) marking a gradient of maturity toward the dopaminergic phenotype along the mitral-glomerular axis. Finally, we propose that the establishment of a synaptic contact with the olfactory nerve is the key event allowing these cells to complete their differentiation toward the DA phenotype and to reach their final destination.

Foveal Depression and Related Factors in Patients with a History of Retinopathy of Prematurity.

PubMed

Miki, Akiko; Honda, Shigeru; Inoue, Yukako; Yamada, Yuko; Nakamura, Makoto

2018-05-09

This study evaluates optical coherence tomography (OCT) findings of the macula in patients with a history of retinopathy of prematurity (ROP). We enrolled 112 patients (age: 6-15 years) and categorized them into 3 groups: gestational age (GA) < 36 weeks with or without a history of ROP (ROP group, preterm group) and GA ≥37 weeks. We included 1 eye of each patient and measured the retinal thickness of the macula by OCT. The ROP group demonstrated the worst VA and the shallowest foveal depression. Furthermore, foveal depression significantly correlated with birth weight, GA, ganglion cell layer/inner plexiform layer (GCL-IPL) thickness, and a history of ROP. This study established a correlation of fovea formation with premature birth, damage of GCL-IPL, and a history of ROP. The retention of the inner retina possibly contributes to abnormal foveal morphology in patients with a history of ROP. © 2018 S. Karger AG, Basel.

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath Tumors and Plexiform Neurofibromas

DTIC Science & Technology

2013-02-01

successfully establish the xenograft within the sciatic nerve. Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform...intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural NF1 MPNST and PNs in scid mice as described by Perrin et...using convection-enhanced delivery ( CED ). Relative Growth of MPNST cells in vivo treated with rapamycin, imatinib or erlotinib: Elotinib

Retina ganglion cell/inner plexiform layer and peripapillary nerve fiber layer thickness in patients with acromegaly.

PubMed

Şahin, Muhammed; Şahin, Alparslan; Kılınç, Faruk; Yüksel, Harun; Özkurt, Zeynep Gürsel; Türkcü, Fatih Mehmet; Pekkolay, Zafer; Soylu, Hikmet; Çaça, İhsan

2017-06-01

Increased secretion of growth hormone and insulin-like growth factor-1 in acromegaly has various effects on multiple organs. However, the ocular effects of acromegaly have yet to be investigated in detail. The aim of the present study was to compare retina ganglion cell/inner plexiform layer (GCIPL) and peripapillary nerve fiber layer thickness (pRNFL) between patients with acromegaly and healthy control subjects using spectral domain optical coherence tomography (SD-OCT). This cross-sectional, comparative study included 18 patients with acromegaly and 20 control subjects. All participants underwent SD-OCT to measure pRNFL (in the seven peripapillary areas), GCIPL (in the nine ETDRS areas), and central macular thickness (CMT). Visual field (VF) examinations were performed using a Humphrey field analyzer in acromegalic patients. Measurements were compared between patients with acromegaly and control subjects. A total of 33 eyes of 18 patients with acromegaly and 40 eyes of 20 control subjects met the inclusion criteria of the present study. The overall calculated average pRNFL thickness was significantly lower in patients with acromegaly than in control subjects (P = 0.01), with pRNFL thickness significantly lower in the temporal superior and temporal inferior quadrants. Contrary to our expectations, pRNFL thickness in the nasal quadrant was similar between acromegalic and control subjects. The mean overall pRNFL thickness and superonasal, nasal, inferonasal, and inferotemporal quadrant pRNFL thicknesses were found to correlate with the mean deviation (MD) according to Spearman's correlation. However, other quadrants were not correlated with VF sensitivity. No significant difference in CMT values was observed (P = 0.6). GCIPL thickness was significantly lower in all quadrants of the inner and outer macula, except for central and inferior outer quadrants, in the acromegaly group than that in the control group (P < 0.05). GCIPL thicknesses of the inferior inner and outer macula quadrants were found to correlate with MD, whereas no correlation was observed between other quadrants and VF sensitivity. We demonstrated that GCIPL thickness decreased in patients with acromegaly compared with that in control subjects. However, the nasal quadrant pRNFL thickness was similar in acromegaly, in contrast to our expectations. SD-OCT may have utility in the assessment of the effects of acromegaly on retinal structures.

Glaucoma diagnostic ability of ganglion cell-inner plexiform layer thickness differs according to the location of visual field loss.

PubMed

Shin, Hye-Young; Park, Hae-Young Lopilly; Jung, Kyoung-In; Choi, Jin-A; Park, Chan Kee

2014-01-01

To determine whether the ganglion cell-inner plexiform layer (GCIPL) or circumpapillary retinal nerve fiber layer (cpRNFL) is better at distinguishing eyes with early glaucoma from normal eyes on the basis of the the initial location of the visual field (VF) damage. Retrospective, observational study. Eighty-four patients with early glaucoma and 43 normal subjects were enrolled. The patients with glaucoma were subdivided into 2 groups according to the location of VF damage: (1) an isolated parafoveal scotoma (PFS, N = 42) within 12 points of a central 10 degrees in 1 hemifield or (2) an isolated peripheral nasal step (PNS, N = 42) within the nasal periphery outside 10 degrees of fixation in 1 hemifield. All patients underwent macular and optic disc scanning using Cirrus high-definition optical coherence tomography (Carl Zeiss Meditec, Dublin, CA). The GCIPL and cpRNFL thicknesses were compared between groups. Areas under the receiver operating characteristic curves (AUCs) were calculated. Comparison of diagnostic ability using AUCs. The average and minimum GCIPL of the PFS group were significantly thinner than those of the PNS group, whereas there was no significant difference in the average retinal nerve fiber layer (RNFL) thickness between the 2 groups. The AUCs of the average (0.962) and minimum GCIPL (0.973) thicknesses did not differ from that of the average RNFL thickness (0.972) for discriminating glaucomatous changes between normal and all glaucoma eyes (P =0.566 and 0.974, respectively). In the PFS group, the AUCs of the average (0.988) and minimum GCIPL (0.999) thicknesses were greater than that of the average RNFL thickness (0.961, P =0.307 and 0.125, respectively). However, the AUCs of the average (0.936) and minimum GCIPL (0.947) thicknesses were lower than that of the average RNFL thickness (0.984) in the PNS group (P =0.032 and 0.069, respectively). The GCIPL parameters were more valuable than the cpRNFL parameters for detecting glaucoma in eyes with parafoveal VF loss, and the cpRNFL parameters were better than the GCIPL parameters for detecting glaucoma in eyes with peripheral VF loss. Clinicians should know that the diagnostic capability of macular GCIPL parameters depends largely on the location of the VF loss. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Genetic and Epigenetic Differences in Monozygotic Twins with NF1

DTIC Science & Technology

2011-10-01

second hit event as a likely etiology for these tumors. Three pairs of twins were discordant for scoliosis , and one pair was concordant for scoliosis ...have included: plexiform neurofibromas (number and location), scoliosis , and malignancy (MPNST). Correlation between CNVs and clinical phenotype will...D E Age (years) 18 10 9 6 5 Gender F F F F F CAL#s Cut. NF Lisch Plexiform# OPG T2 Hyperint Scoliosis Pectus MPNST MR LD Speech ADHD

Parallel odor processing by mitral and middle tufted cells in the olfactory bulb.

PubMed

Cavarretta, Francesco; Burton, Shawn D; Igarashi, Kei M; Shepherd, Gordon M; Hines, Michael L; Migliore, Michele

2018-05-16

The olfactory bulb (OB) transforms sensory input into spatially and temporally organized patterns of activity in principal mitral (MC) and middle tufted (mTC) cells. Thus far, the mechanisms underlying odor representations in the OB have been mainly investigated in MCs. However, experimental findings suggest that MC and mTC may encode parallel and complementary odor representations. We have analyzed the functional roles of these pathways by using a morphologically and physiologically realistic three-dimensional model to explore the MC and mTC microcircuits in the glomerular layer and deeper plexiform layer. The model makes several predictions. MCs and mTCs are controlled by similar computations in the glomerular layer but are differentially modulated in deeper layers. The intrinsic properties of mTCs promote their synchronization through a common granule cell input. Finally, the MC and mTC pathways can be coordinated through the deep short-axon cells in providing input to the olfactory cortex. The results suggest how these mechanisms can dynamically select the functional network connectivity to create the overall output of the OB and promote the dynamic synchronization of glomerular units for any given odor stimulus.

Jupiter's evolution with primordial composition gradients

NASA Astrophysics Data System (ADS)

Vazan, Allona; Helled, Ravit; Guillot, Tristan

2018-02-01

Recent formation and structure models of Jupiter suggest that the planet can have composition gradients and not be fully convective (adiabatic). This possibility directly affects our understanding of Jupiter's bulk composition and origin. In this Letter we present Jupiter's evolution with a primordial structure consisting of a relatively steep heavy-element gradient of 40 M⊕. We show that for a primordial structure with composition gradients, most of the mixing occurs in the outer part of the gradient during the early evolution (several 107 yr), leading to an adiabatic outer envelope (60% of Jupiter's mass). We find that the composition gradient in the deep interior persists, suggesting that 40% of Jupiter's mass can be non-adiabatic with a higher temperature than the one derived from Jupiter's atmospheric properties. The region that can potentially develop layered convection in Jupiter today is estimated to be limited to 10% of the mass. Movies associated to Figs. 1-3 are available at http://https://www.aanda.org

Evaluation of inner retinal layers as biomarkers in mild cognitive impairment to moderate Alzheimer’s disease

PubMed Central

Mukherjee, Dibyendu; Stinnett, Sandra S.; Cousins, Scott W.; Potter, Guy G.; Burke, James R.; Farsiu, Sina; Whitson, Heather E.

2018-01-01

Inner retina in Alzheimer's Disease (AD) may experience neuroinflammation resulting in atrophy. The objective of our study was to determine whether retinal GCIPL (ganglion cell-inner plexiform layer) or nerve fiber layer (NFL) thickness may serve as noninvasive biomarkers to diagnose AD. This cross-sectional case-control study enrolled 15 mild cognitive impairment (MCI) patients, 15 mild-moderate AD patients, and 18 cognitively normal adults. NFL and GCIPL thicknesses on optical coherence tomography (OCT) were measured using Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP) and Spectralis software. We demonstrated that regional thicknesses of NFL or GCIPL on macular or nerve OCTs did not differ between groups. However, a multi-variate regression analysis identified macular areas with a significant thickening or thinning in NFL and GCIPL in MCI and AD patients. Our primary findings controvert previous reports of thinner NFL in moderate-to-severe AD. The areas of thickening of GCIPL and NFL in the macula adjacent to areas of thinning, as revealed by a more complex statistical model, suggest that NFL and GCIPL may undergo dynamic changes during AD progression. PMID:29420642

Origin of the DA and non-DA white dwarf stars

NASA Technical Reports Server (NTRS)

Shipman, Harry L.

1989-01-01

Various proposals for the bifurcation of the white dwarf cooling sequence are reviewed. 'Primordial' theories, in which the basic bifurcation of the white dwarf sequence is rooted in events predating the white dwarf stage of stellar evolution, are discussed, along with the competing 'mixing' theories in which processes occurring during the white dwarf stage are responsible for the existence of DA or non-DA stars. A new proposal is suggested, representing a two-channel scenario. In the DA channel, some process reduces the hydrogen layer mass to the value of less than 10 to the -7th. The non-DA channel is similar to that in the primordial scenario. These considerations suggest that some mechanism operates in both channels to reduce the thickness of the outermost layer of the white dwarf. It is also noted that accretion from the interstellar medium has little to do with whether a particular white dwarf becomes a DA or a non-DA star.

Catastrophic disruptions as the origin of bilobate comets

NASA Astrophysics Data System (ADS)

Schwartz, Stephen R.; Michel, Patrick; Jutzi, Martin; Marchi, Simone; Zhang, Yun; Richardson, Derek C.

2018-05-01

Several comets observed at close range have bilobate shapes1, including comet 67P/Churyumov-Gerasimenko (67P/C-G), which was imaged by the European Space Agency's Rosetta mission2,3. Bilobate comets are thought to be primordial because they are rich in supervolatiles (for example, N2 and CO) and have a low bulk density, which implies that their formation requires a very low-speed accretion of two bodies. However, slow accretion does not only occur during the primordial phase of the Solar System; it can also occur at later epochs as part of the reaccumulation process resulting from the collisional disruption of a larger body4, so this cannot directly constrain the age of bilobate comets. Here, we show by numerical simulation that 67P/C-G and other elongated or bilobate comets can be formed in the wake of catastrophic collisional disruptions of larger bodies while maintaining their volatiles and low density throughout the process. Since this process can occur at any epoch of our Solar System's history, from early on through to the present day5, there is no need for these objects to be formed primordially. These findings indicate that observed prominent geological features, such as pits and stratified surface layers4,5, may not be primordial.

Twenty years of embryonic stem cell research in farm animals

USDA-ARS?s Scientific Manuscript database

Notable distinctions between an embryonic stem cell (ESC) and somatic cell are that the ESC can maintain an undifferentiated state indefinitely, self renew, and is pluripotent, meaning that the ESC can potentially generate cells representing all the three primordial germ layers and contribute to the...

Neuronal plasticity depending on a glycoprotein synthesized in goldfish leptomeninx.

PubMed

Schmidt, R; Rother, S; Schlingensiepen, K H; Brysch, W

1992-01-01

Transcription of a calcium and zinc binding, nervous system-specific cell adhesion glycoprotein, ependymin, in goldfish leptomeninx was significantly enhanced after active avoidance conditioning, followed by enhanced translation and secretion. Inactivation of secreted ependymin by injected antisera interfered with behavioral adaptations. In addition to the site of synthesis in reticular cells of the leptomeninx electronmicroscopic immunochemistry localized the protein to tectal neurons of the superficial plexiform and the periventricular cell layers. Detection of ependymin in cells where it is not synthesized, namely in neurons, suggests a re-uptake during functional activity of the CNS and assigns a pivotal role to the cerebrospinal and interstitial brain fluids for the distribution of protein factors that support axonal growth and neuronal plasticity.

Compositional layering within the large low shear-wave velocity provinces (LLSVPs) in the lower mantle

NASA Astrophysics Data System (ADS)

Ballmer, Maxim; Lekic, Vedran; Schumacher, Lina; Ito, Garrett; Thomas, Christine

2016-04-01

Seismic tomography reveals two antipodal LLSVPs in the Earth's mantle, each extending from the core-mantle boundary (CMB) up to ~1000 km depth. The LLSVPs are thought to host primordial mantle materials that bear witness of early-Earth processes, and/or subducted basalt that has accumulated in the mantle over billions of years. A compositional distinction between the LLSVPs and the ambient mantle is supported by anti-correlation of bulk-sound and shear-wave velocity (Vs) anomalies as well as abrupt lateral gradients in Vs along LLSVP margins. Both of these observations, however, are mainly restricted to the LLSVP bottom domains (2300~2900 km depth), or hereinafter referred to as "deep distinct domains" (DDD). Seismic sensitivity calculations suggest that DDDs are more likely to be composed of primordial mantle material than of basaltic material. On the other hand, the seismic signature of LLSVP shallow domains (1000~2300 km depth) is consistent with a basaltic composition, though a purely thermal origin cannot be ruled out. Here, we explore the dynamical, seismological, and geochemical implications of the hypothesis that the LLSVPs are compositionally layered with a primordial bottom domain (or DDD) and a basaltic shallow domain. We test this hypothesis using 2D thermochemical mantle-convection models. Depending on the density difference between primordial and basaltic materials, the materials either mix or remain separate as they join to form thermochemical piles in the deep mantle. Separation of both materials within these piles provides an explanation for LLSVP seismic properties, including substantial internal vertical gradients in Vs observed at 400-700 km height above the CMB, as well as out-of-plane reflections on LLSVP sides over a range of depths. Predicted geometry of thermochemical piles is compared to LLSVP and DDD shapes as constrained by seismic cluster analysis. Geodynamic models predict short-lived "secondary" plumelets to rise from LLSVP roofs and to entrain basaltic material that has evolved in the lower mantle. Long-lived "primary" plumes rise from LLSVP margins and entrain a mix of materials, including small fractions of primordial mantle material. These predictions address the geochemical and geochronological record of intraplate hotspot volcanism on the Pacific plate. In general, the parameter range spanned by models that are able to reconcile observations provides a constraint for the intrinsic density anomaly (or composition) of DDDs. We use this constraint to evaluate a possible origin of DDDs from (basal) magma ocean cumulates. The study of LLSVP compositional layering has indeed important implications for our understanding of heat and material fluxes through mantle reservoirs, as well as bulk Earth chemistry and evolution.

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.

Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis.

PubMed

Petzold, Axel; Balcer, Laura J; Calabresi, Peter A; Costello, Fiona; Frohman, Teresa C; Frohman, Elliot M; Martinez-Lapiscina, Elena H; Green, Ari J; Kardon, Randy; Outteryck, Olivier; Paul, Friedemann; Schippling, Sven; Vermersch, Patrik; Villoslada, Pablo; Balk, Lisanne J

2017-10-01

Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT. In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified data on eyes into healthy controls, multiple-sclerosis-associated optic neuritis (MSON), and multiple sclerosis without optic neuritis (MSNON). We assessed thickness of the retinal layers and we rated individual layer segmentation performance by random effects meta-analysis for MSON eyes versus control eyes, MSNON eyes versus control eyes, and MSNON eyes versus MSON eyes. We excluded relevant sources of bias by funnel plots. Of 25 497 records identified, 110 articles were eligible and 40 reported data (in total 5776 eyes from patients with multiple sclerosis [1667 MSON eyes and 4109 MSNON eyes] and 1697 eyes from healthy controls) that met published OCT quality control criteria and were suitable for meta-analysis. Compared with control eyes, the peripapillary retinal nerve fibre layer (RNFL) showed thinning in MSON eyes (mean difference -20·10 μm, 95% CI -22·76 to -17·44; p<0·0001) and in MSNON eyes (-7·41 μm, -8·98 to -5·83; p<0·0001). The macula showed RNFL thinning of -6·18 μm (-8·07 to -4·28; p<0·0001) in MSON eyes and -2·15 μm (-3·15 to -1·15; p<0·0001) in MSNON eyes compared with control eyes. Atrophy of the macular ganglion cell layer and inner plexiform layer (GCIPL) was -16·42 μm (-19·23 to -13·60; p<0·0001) for MSON eyes and -6·31 μm (-7·75 to -4·87; p<0·0001) for MSNON eyes compared with control eyes. A small degree of inner nuclear layer (INL) thickening occurred in MSON eyes compared with control eyes (0·77 μm, 0·25 to 1·28; p=0·003). We found no statistical difference in the thickness of the combined outer nuclear layer and outer plexiform layer when we compared MSNON or MSON eyes with control eyes, but we found a small degree of thickening of the combined layer when we compared MSON eyes with MSNON eyes (1·21 μm, 0·24 to 2·19; p=0·01). The largest and most robust differences between the eyes of people with multiple sclerosis and control eyes were found in the peripapillary RNFL and macular GCIPL. Inflammatory disease activity might be captured by the INL. Because of the consistency, robustness, and large effect size, we recommend inclusion of the peripapillary RNFL and macular GCIPL for diagnosis, monitoring, and research. None. Copyright © 2017 Elsevier Ltd. All rights reserved.

Embryological evidence for a possible polyphyletic origin of the recent amphibians.

PubMed

Nieuwkoop, P D; Sutasurya, L A

1976-02-01

The markedly different mode of mesoderm formation in anuran and urodelan amphibians (which is related to the early double-layered nature of the anuran blastula wall in contrast to its single-layered nature in the urodeles), but particularly the fundamentally different place and mode of origin of the primordial germ cells in the two groups of amphibians, strongly pleads in favour of a very ancient bifurcation in the phylogenetic history of the two groups, even suggesting a polyphyletic origin from different ancestral fishes.

Changes in Inner and Outer Retinal Layer Thicknesses after Vitrectomy for Idiopathic Macular Hole: Implications for Visual Prognosis

PubMed Central

Hashimoto, Yuki; Saito, Wataru; Fujiya, Akio; Yoshizawa, Chikako; Hirooka, Kiriko; Mori, Shohei; Noda, Kousuke; Ishida, Susumu

2015-01-01

Purpose To investigate sequential post-operative thickness changes in inner and outer retinal layers in eyes with an idiopathic macular hole (MH). Methods Retrospective case series. Twenty-four eyes of 23 patients who had received pars plana vitrectomy (PPV) for the closure of MH were included in the study. Spectral domain optical coherence tomography C-scan was used to automatically measure the mean thickness of the inner and outer retinal layers pre-operatively and up to 6 months following surgery. The photoreceptor outer segment (PROS) length was measured manually and was used to assess its relationship with best-corrected visual acuity (BCVA). Results Compared with the pre-operative thickness, the inner layers significantly thinned during follow-up (P = 0.02), particularly in the parafoveal (P = 0.01), but not perifoveal, area. The post-operative inner layer thinning ranged from the ganglion cell layer to the inner plexiform layer (P = 0.002), whereas the nerve fiber layer was unaltered. Outer layer thickness was significantly greater post-operatively (P = 0.002), and especially the PROS lengthened not only in the fovea but also in the parafovea (P < 0.001). Six months after surgery, BCVA was significantly correlated exclusively with the elongated foveal PROS (R = 0.42, P = 0.03), but not with any of the other thickness parameters examined. Conclusions Following PPV for MH, retinal inner layers other than the nerve fiber layer thinned, suggestive of subclinical thickening in the inner layers where no cyst was evident pre-operatively. In contrast, retinal outer layer thickness significantly increased, potentially as a result of PROS elongation linking tightly with favorable visual prognosis in MH eyes. PMID:26291526

Type VII Collagen Expression in the Human Vitreoretinal Interface, Corpora Amylacea and Inner Retinal Layers

PubMed Central

Wullink, Bart; Pas, Hendri H.; Van der Worp, Roelofje J.; Kuijer, Roel; Los, Leonoor I.

2015-01-01

Type VII collagen, as a major component of anchoring fibrils found at basement membrane zones, is crucial in anchoring epithelial tissue layers to their underlying stroma. Recently, type VII collagen was discovered in the inner human retina by means of immunohistochemistry, while proteomic investigations demonstrated type VII collagen at the vitreoretinal interface of chicken. Because of its potential anchoring function at the vitreoretinal interface, we further assessed the presence of type VII collagen at this site. We evaluated the vitreoretinal interface of human donor eyes by means of immunohistochemistry, confocal microscopy, immunoelectron microscopy, and Western blotting. Firstly, type VII collagen was detected alongside vitreous fibers6 at the vitreoretinal interface. Because of its known anchoring function, it is likely that type VII collagen is involved in vitreoretinal attachment. Secondly, type VII collagen was found within cytoplasmic vesicles of inner retinal cells. These cells resided most frequently in the ganglion cell layer and inner plexiform layer. Thirdly, type VII collagen was found in astrocytic cytoplasmic inclusions, known as corpora amylacea. The intraretinal presence of type VII collagen was confirmed by Western blotting of homogenized retinal preparations. These data add to the understanding of vitreoretinal attachment, which is important for a better comprehension of common vitreoretinal attachment pathologies. PMID:26709927

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

PubMed

Juric-Sekhar, Gordana; Kapur, Raj P; Glass, Ian A; Murray, Mitzi L; Parnell, Shawn E; Hevner, Robert F

2011-04-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

Not all Primordial Noble Gas Signatures are Associated with OIBs and Mantle Plumes - Mantle Heterogeneity, Primordial Shallow Sources and a Solar-like He, Ne Signature in an Ancient North American Craton

NASA Astrophysics Data System (ADS)

Ma, L.; Castro, M. C.; Hall, C. M.

2007-12-01

The presence of primordial He and Ne components in ocean island basalts (OIBs) as well as a mantle He/heat flux ratio lower than the production ratio near mid-ocean ridges have historically been used to support the existence of a two-layer mantle convection model. This would comprise a lower, primordial, undegassed reservoir from which He removal to the upper degassed mantle would be impeded. Arguments based on He and heat transport have been recently invalidated by Castro et al. (2005) and should no longer be used to justify the presence of two such distinct mantle reservoirs. Indeed, it was shown that such low He/heat flux ratios are expected and do not reflect a He deficit in the original crust or mantle reservoir. By contrast, the occurrence of a He/heat flux ratio greater than the radiogenic production ratio can only result from a past mantle thermal event in which the released heat has already escaped while the released He remains, and is slowly rising to the surface. Such a high He/heat flux ratio is present in shallow groundwaters of the Michigan Basin. We now present results of a new noble gas study conducted in the Michigan Basin, in which 38 deep (0.5-3.6km) brine samples were collected and analyzed for all noble gas abundances and isotopic ratios. As expected from previously computed shallow high He/heat flux ratios, both He and Ne isotopic ratios clearly indicate the presence of a mantle component. Of greater significance is the primordial, solar-like signature, of this mantle component. It is also the first primordial signature ever recorded in crustal fluids in a continental region. Because no hotspots or hotspot tracks are known in the area, it is highly unlikely for such primordial, solar-like signature to result from a mantle plume-related mechanism originating deep in the mantle. We argue that such a primordial signature can be explained by a shallow noble gas reservoir in the subcontinental lithospheric mantle (SCLM) beneath the Michigan Basin, possibly created by a mechanism similar to that proposed by Anderson (1998) for oceanic regions. Indeed, the Michigan Basin, located within the ancient North American craton (~1.1->2.5Ga), lies on a very thick U-Th depleted SCLM, possibly allowing preservation of a primordial, residual, mantle reservoir beneath the continental crust. Recent reactivation of the old mid-continent rift transecting the crystalline basement is likely responsible for the release of this primordial signature into the basin. The solar-like He and Ne signatures present in the Michigan Basin fluids not only suggest that a deep primordial mantle reservoir is not required to explain the presence of such components, they also point to a very heterogeneous mantle as previously suggested by Anderson (1998), Albarede (2005), and others. Consequently, the presence of a primordial noble gas signature, at least if observed in a continental region, should not be used to conclude at the existence of a deep mantle source and thus, of a hotspot as typically defined. The SCLM underneath ancient cratons is a great candidate for hosting primitive ancient mantle reservoirs. Arguments based on He/heat flux ratios as well as the presence of a primordial noble gas signature should not be used to support the existence of a lower, primordial, versus an upper, degassed mantle reservoir. Our study provides the first observational case for long-term primordial lithospheric storage. Anderson, 1998, Proc. Natl. Acad. Sci. USA, 95, 9087-9092. Albarede, 2005, AGU Monograph, 160, 27-46. Castro et al., 2005, EPSL, 237, 893-910.

The RNA-binding protein Musashi-1 is produced in the developing and adult mouse eye.

PubMed

Raji, B; Dansault, A; Leemput, J; de la Houssaye, G; Vieira, V; Kobetz, A; Arbogast, L; Masson, C; Menasche, M; Abitbol, M

2007-08-10

Musashi-1 (Msi1) is an RNA-binding protein produced in various types of stem cells including neural stem/progenitor cells and astroglial progenitor cells in the vertebrate central nervous system. Other RNA-binding proteins such as Pumilio-1, Pumilio-2, Staufen-1, and Staufen-2 have been characterized as potential markers of several types of stem or progenitor cells. We investigated the involvement of Msi1 in mouse eye development and adult mouse eye functions by analyzing the profile of Msi1 production in all ocular structures during development and adulthood. We studied Msi1 production by in situ hybridization and immunohistochemistry of ocular tissue sections and by semi-quantitative RT-PCR and western blot analysis from the embryonic stage of 12.5 days post coitum (E12.5 dpc) when the first retinal ganglion cells (RGCs) begin to appear to the adult stage when all retinal cell types are present. Msi1 mRNA was present at all studied stages of eye development. Msi1 protein was detected in the primitive neuroblastic layer (NbL), the ganglion cell layer (GCL), and in all major differentiated neurons of postnatal developing and adult retinae. During postnatal developing stages, faint diffuse Msi1 protein staining is converted to a more specific distribution once mouse retina is fully differentiated. The most striking result of our study concerns the large amounts of Msi1 protein and mRNA in several unexpected sites of adult mouse eyes including the corneal epithelium and endothelium, stromal keratocytes, progenitor cells of the limbus, equatorial lens stem cells, differentiated lens epithelial cells, and differentiating lens fibers. Msi1 was also found in the pigmented and nonpigmented cells of the ciliary processes, the melanocytes of the ciliary body, the retinal pigment epithelium, differentiated retinal neurons, and most probably in the retinal glial cells such as Müller glial cells, astrocytes, and the oligodendocytes surrounding the axons of the optic nerve. Msi1 expression was detected in the outer plexiform layer, the inner plexiform layer, and the nerve fiber layer of fully differentiated adult retina. We provide here the first demonstration that the RNA-binding protein, Msi1, is produced in mouse eyes from embryonic stages until adulthood. The relationship between the presence of Msi1 in developing ocular compartments and the possible stem/progenitor cell characteristics of these compartments remains unclear. Finally, the expression of Msi1 in several different cell types in the adult eye is extremely intriguing and should lead to further attempts to unravel the role of Msi1 in cellular and subcellular RNA metabolism and in the control of translational processes in adult eye cells particularly in adult neuronal dendrites, axons, and synapses.

Immunocytochemical localization of calretinin containing neurons in retina from rabbit, cat, and dog.

PubMed

Jeon, M H; Jeon, C J

1998-09-01

Calcium homeostasis is critical for many neuronal functions, yet the distribution of calcium-binding protein is not always conserved among species, even between closely related species. We decided therefore to study the distribution of one of these calcium-binding proteins calretinin, in retina from rabbit, cat, and dog. Calretinin was localized using antibody immunocytochemistry. Calretinin immunoreactivity was found in numerous cell bodies in the ganglion cell layer in all three animals. These cells had small to medium-sized somas. Large ganglion cells, however, were not labeled using antiserum against calretinin. In the inner nuclear layer, calretinin immunoreactivity was found in many neurons in all three species. The regular distribution of neurons, the inner marginal location of their cell bodies in the inner nuclear layer, and the distinctive bilaminar morphologies of their dendritic arbors in the inner plexiform layer suggested that these calretinin-positive cells were AII amacrine cells. Calretinin immunoreactivity was observed in both A- and B-type horizontal cells in cat and dog retina. However, horizontal cells in the rabbit retina were not labeled by this antibody. Neurons in the photoreceptor cell layer were not labeled by this antibody. The present study suggests that calretinin immunoreactivity is present in several populations in the retina. In particular, calretinin labels AII amacrine cells and a subpopulation of ganglion cells in all three animals. Horizontal cells, however, were not labeled in rabbit.

Different foveal schisis patterns in each retinal layer in eyes with hereditary juvenile retinoschisis evaluated by en-face optical coherence tomography.

PubMed

Yoshida-Uemura, Tomoyo; Katagiri, Satoshi; Yokoi, Tadashi; Nishina, Sachiko; Azuma, Noriyuki

2017-04-01

To analyze the structures of schisis in eyes with hereditary juvenile retinoschisis using en-face optical coherence tomography (OCT) imaging. In this retrospective observational study, we reviewed the medical records of patients with hereditary juvenile retinoschisis who underwent comprehensive ophthalmic examinations including swept-source OCT. OCT images were obtained from 16 eyes of nine boys (mean age ± standard deviation, 10.6 ± 4.0 years). The horizontal OCT images at the fovea showed inner nuclear layer (INL) schisis in one eye (6.3 %), ganglion cell layer (GCL) and INL schisis in 12 eyes (75.0 %), INL and outer plexiform layer (OPL) schisis in two eyes (12.5 %), and GCL, INL, and OPL schisis in one eye (6.3 %). En-face OCT images showed characteristic schisis patterns in each retinal layer, which were represented by multiple hyporeflective holes in the parafoveal region in the GCL, a spoke-like pattern in the foveal region, a reticular pattern in the parafoveal region in the INL, and multiple hyporeflective polygonal cavities with partitions in the OPL. Our results using en-face OCT imaging clarified different patterns of schisis formation among the GCL, INL, and OPL, which lead to further recognition of structure in hereditary juvenile retinoschisis.

Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation.

PubMed

Chen, Ding; Xu, Tao; Tu, Mengjun; Xu, Jinlin; Zhou, Chenchen; Cheng, Lulu; Yang, Ruqing; Yang, Tanchu; Zheng, Weiwei; He, Xiubin; Deng, Ruzhi; Ge, Xianglian; Li, Jin; Song, Zongming; Zhao, Junzhao; Gu, Feng

2017-01-01

X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1), which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have the exact mutation identified in the patients is extremely crucial, and that the way which genome editing in knock-in animals could be easily transferred to the patients. Here we recruited a family diagnosed with XLRS and identified the causative mutation ( RS1 , p.Y65X), then a knock-in mouse model harboring this disease-causative mutation was generated via TALEN (transcription activator-like effector nucleases). We found that the b-wave amplitude of the ERG of the RS1 -KI mice was significantly decreased. Moreover, we observed that the structure of retina in RS1 -KI mice has become disordered, including the disarray of inner nuclear layer and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments of photoreceptor and the loss of outer segments. The novel knock-in mice ( RS1 -KI) harboring patient-specific mutation will be valuable for development of treatment via genome editing mediated gene correction.

Changes in Macular Retinal Layers and Peripapillary Nerve Fiber Layer Thickness after 577-nm Pattern Scanning Laser in Patients with Diabetic Retinopathy

PubMed Central

Shin, Ji Soo

2017-01-01

Purpose The aim of this study was to evaluate the changes in thickness of each macular retinal layer, the peripapillary retinal nerve fiber layer (RNFL), and central macular thickness (CMT) after 577-nm pattern scanning laser (PASCAL) photocoagulation in patients with diabetic retinopathy. Methods This retrospective study included 33 eyes with diabetic retinopathy that underwent 577-nm PASCAL photocoagulation. Each retinal layer thickness, peripapillary RNFL thickness, and CMT were measured by spectral-domain optical coherence tomography before 577-nm PASCAL photocoagulation, as well as at 1, 6, and 12 months after 577-nm PASCAL photocoagulation. Computerized intraretinal segmentation of optical coherence tomography was performed to identify the thickness of each retinal layer. Results The average thickness of the RNFL, ganglion cell layer, inner plexiform layer, inner nuclear layer, inner retinal layer, and CMT at each follow-up increased significantly from baseline (p < 0.001), whereas that of the retinal pigment epithelium at each follow-up decreased significantly from baseline (p < 0.001). The average thickness of the peripapillary RNFL increased significantly at one month (p < 0.001). This thickness subsequently recovered to 7.48 µm, and there were no significant changes at six or 12 months compared to baseline (p > 0.05). Conclusions Each macular retinal layer and CMT had a tendency to increase for one year after 577-nm PASCAL photocoagulation, whereas the average thickness of retinal pigment epithelium decreased at one-year follow-up compared to the baseline. Although an increase in peripapillary RNFL thickness was observed one month after 577-nm PASCAL photocoagulation, there were no significant changes at the one-year follow-up compared to the baseline. PMID:29022292

Changes in Macular Retinal Layers and Peripapillary Nerve Fiber Layer Thickness after 577-nm Pattern Scanning Laser in Patients with Diabetic Retinopathy.

PubMed

Shin, Ji Soo; Lee, Young Hoon

2017-12-01

The aim of this study was to evaluate the changes in thickness of each macular retinal layer, the peripapillary retinal nerve fiber layer (RNFL), and central macular thickness (CMT) after 577-nm pattern scanning laser (PASCAL) photocoagulation in patients with diabetic retinopathy. This retrospective study included 33 eyes with diabetic retinopathy that underwent 577-nm PASCAL photocoagulation. Each retinal layer thickness, peripapillary RNFL thickness, and CMT were measured by spectral-domain optical coherence tomography before 577-nm PASCAL photocoagulation, as well as at 1, 6, and 12 months after 577-nm PASCAL photocoagulation. Computerized intraretinal segmentation of optical coherence tomography was performed to identify the thickness of each retinal layer. The average thickness of the RNFL, ganglion cell layer, inner plexiform layer, inner nuclear layer, inner retinal layer, and CMT at each follow-up increased significantly from baseline (p < 0.001), whereas that of the retinal pigment epithelium at each follow-up decreased significantly from baseline (p < 0.001). The average thickness of the peripapillary RNFL increased significantly at one month (p < 0.001). This thickness subsequently recovered to 7.48 μm, and there were no significant changes at six or 12 months compared to baseline (p > 0.05). Each macular retinal layer and CMT had a tendency to increase for one year after 577-nm PASCAL photocoagulation, whereas the average thickness of retinal pigment epithelium decreased at one-year follow-up compared to the baseline. Although an increase in peripapillary RNFL thickness was observed one month after 577-nm PASCAL photocoagulation, there were no significant changes at the one-year follow-up compared to the baseline. © 2017 The Korean Ophthalmological Society

Quantification of Peripapillary Sparing and Macular Involvement in Stargardt Disease (STGD1)

PubMed Central

Rhee, David W.; Smith, R. Theodore; Tsang, Stephen H.; Allikmets, Rando; Chang, Stanley; Lazow, Margot A.; Hood, Donald C.; Greenstein, Vivienne C.

2011-01-01

Purpose. To quantify and compare structure and function across the macula and peripapillary area in Stargardt disease (STGD1). Methods. Twenty-seven patients (27 eyes) and 12 age-similar controls (12 eyes) were studied. Patients were classified on the basis of full-field electroretinogram (ERG) results. Fundus autofluorescence (FAF) and spectral domain-optical coherence tomography (SD-OCT) horizontal line scans were obtained through the fovea and peripapillary area. The thicknesses of the outer nuclear layer plus outer plexiform layer (ONL+), outer segment (OS), and retinal pigment epithelium (RPE) were measured through the fovea, and peripapillary areas from 1° to 4° temporal to the optic disc edge using a computer-aided, manual segmentation technique. Visual sensitivities in the central 10° were assessed using microperimetry and related to retinal layer thicknesses. Results. Compared to the central macula, the differences between controls and patients in ONL+, OS, and RPE layer thicknesses were less in the nasal and temporal macula. Relative sparing of the ONL+ and/or OS layers was detected in the nasal (i.e., peripapillary) macula in 8 of 13 patients with extramacular disease on FAF; relative functional sparing was also detected in this subgroup. All 14 patients with disease confined to the central macula, as detected on FAF, showed ONL+ and OS layer thinning in regions of normal RPE thickness. Conclusions. Relative peripapillary sparing was detected in STGD1 patients with extramacular disease on FAF. Photoreceptor thinning may precede RPE degeneration in STGD1. PMID:21873672

Ratiometric analysis of optical coherence tomography-measured in vivo retinal layer thicknesses for the detection of early diabetic retinopathy.

PubMed

Bhaduri, Basanta; Shelton, Ryan L; Nolan, Ryan M; Hendren, Lucas; Almasov, Alexandra; Labriola, Leanne T; Boppart, Stephen A

2017-11-01

Influence of diabetes mellitus (DM) and diabetic retinopathy (DR) on parafoveal retinal thicknesses and their ratios was evaluated. Six retinal layer boundaries were segmented from spectral-domain optical coherence tomography images using open-source software. Five study groups: (1) healthy control (HC) subjects, and subjects with (2) controlled DM, (3) uncontrolled DM, (4) controlled DR and (5) uncontrolled DR, were identified. The one-way analyses of variance (ANOVA) between adjacent study groups (i. e. 1 with 2, 2 with 3, etc) indicated differences in retinal thicknesses and ratios. Overall retinal thickness, ganglion cell layer (GCL) thickness, inner plexiform layer (IPL) thickness, and their combination (GCL+ IPL), appeared to be significantly less in the uncontrolled DM group when compared to controlled DM and controlled DR groups. Although the combination of nerve fiber layer (NFL) and GCL, and IPL thicknesses were not different, their ratio, (NFL+GCL)/IPL, was found to be significantly higher in the controlled DM group compared to the HC group. Comparisons of the controlled DR group with the controlled DM group, and with the uncontrolled DR group, do not show any differences in the layer thicknesses, though several significant ratios were obtained. Ratiometric analysis may provide more sensitive parameters for detecting changes in DR. Picture: A representative segmented OCT image of the human retina is shown. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Localization of organ-specific antigens in the nervous system of the rat.

PubMed

Weinrauder, H; Lach, B

1977-08-16

Localization of organ-specific brain antigens in the central nervous system of the rat has been studied by means of indirect immunofluorescence. Rabbit antiserum against homogenate of rat brain, previously absorbed with normal serum and homogenates of rat organs (kidney, liver, spleen), reacted with the water-soluble antigens of rat brain prepared by extraction with phosphate buffer (pH 7.3) and ultracentrifugation at 50 000 X g to give one band in the immunodiffusion test and 2--3 precipitation arcs in immunoelectrophoresis. There was also a positive reaction with peripheral nerve. The antigen was detectable in all regions of the CNS. Cells with distinct cytoplasmic immunofluorescence were most frequently observed in cerebellar white matter, pons, cerebellar pedunculi, longitudinal tracts of the brain stem. Positive immunofluorecence reaction has appeared in the outer plexiform layer and granular layer of the retina, satelite cells of the spinal root ganglia and Schwann cells. A similar reaction was observed in human, mouse and guinea pig brain slices. Both the morphological and immunochemical reactions are indicative of glial localization of this antigen.

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III

PubMed Central

Juric-Sekhar, Gordana; Kapur, Raj P.; Glass, Ian A.; Murray, Mitzi L.; Parnell, Shawn E.

2011-01-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria–lissencephaly. PMID:20857301

Method to investigate temporal dynamics of ganglion and other retinal cells in the living human eye

NASA Astrophysics Data System (ADS)

Kurokawa, Kazuhiro; Liu, Zhuolin; Crowell, James; Zhang, Furu; Miller, Donald T.

2018-02-01

The inner retina is critical for visual processing, but much remains unknown about its neural circuitry and vulnerability to disease. A major bottleneck has been our inability to observe the structure and function of the cells composing these retinal layers in the living human eye. Here, we present a noninvasive method to observe both structural and functional information. Adaptive optics optical coherence tomography (AO-OCT) is used to resolve the inner retinal cells in all three dimensions and novel post processing algorithms are applied to extract structure and physiology down to the cellular level. AO-OCT captured the 3D mosaic of individual ganglion cell somas, retinal nerve fiber bundles of micron caliber, and microglial cells, all in exquisite detail. Time correlation analysis of the AO-OCT videos revealed notable temporal differences between the principal layers of the inner retina. The GC layer was more dynamic than the nerve fiber and inner plexiform layers. At the cellular level, we applied a customized correlation method to individual GCL somas, and found a mean time constant of activity of 0.57 s and spread of +/-0.1 s suggesting a range of physiological dynamics even in the same cell type. Extending our method to slower dynamics (from minutes to one year), time-lapse imaging and temporal speckle contrast revealed appendage and soma motion of resting microglial cells at the retinal surface.

HISTOCHEMICAL INVESTIGATIONS OF GLYCOGEN IN EYEBALL TISSUE IN RADIATION SICKNESS

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

Abdullaev, V.M.

1964-03-01

Dogs and rabbits were irradiated with x-ray doses of 692 and 792 r, respectively. The animals were sacrificed at different periods following irradiation and the enucleated eyeballs embedded in celloidin and paraffin for histochemical study. Glycogen was nonuniformaly distributed as granules, lumps, powder, or a homogeneous mass in the normal coats of the eye. A high glycogen content was found in the eye muscles, conjunctival epithelium, sustentacular fibers of Muller, and vessels, especially those of the iris. There was a medium amount of glycogen in the corneal epithelium, rod and cone layer, ciliary muscles, and muscle bundles of the iris.more » Little glycogen was found in the outer plexiform and inner nuclear layers of the retina and in the substantia propria. Glycogen was lacking in the endothelium of Descemet's membrane and of the iris, the epithelium of the crystalline lens, and the glial cells of the optic nerve. The content and distribution of glycogen changed, depending on the severity and stage of radiation sickness. Increased glycogen content was noted in the eye muscles, outer layers of the retina, and vitreous body. A decrease was noted in the inner layers of the retina, the conjunctival epithelium, and in the nuclei of the crystalline lens. Glycogen disappeared in the crystalline lens in the areas of homogenation and fibrogenesis. (auth)« less

Structural analysis of retinal photoreceptor ellipsoid zone and postreceptor retinal layer associated with visual acuity in patients with retinitis pigmentosa by ganglion cell analysis combined with OCT imaging

PubMed Central

Liu, Guodong; Li, Hui; Liu, Xiaoqiang; Xu, Ding; Wang, Fang

2016-01-01

Abstract The aim of this study was to examine changes in photoreceptor ellipsoid zone (EZ) and postreceptor retinal layer in retinitis pigmentosa (RP) patients by ganglion cell analysis (GCA) combined with optical coherence tomography (OCT) imaging to evaluate the structure–function relationships between retinal layer changes and best corrected visual acuity (BCVA). Sixty-eight eyes of 35 patients with RP and 65 eyes of 35 normal controls were analyzed in the study. The average length of EZ was 911.1 ± 208.8 μm in RP patients, which was shortened with the progression of the disease on the OCT images. The average ganglion cell–inner plexiform layer thickness (GCIPLT) was 54.7 ± 18.9 μm in RP patients, while in normal controls it was 85.6 ± 6.8 μm. The GCIPLT in all quarters became significantly thinner along with outer retinal thinning. There was a significantly positive correlation between BCVA and EZ (r = −0.7622, P < 0.001) and GCIPLT (r = −0.452, P < 0.001). Therefore, we assess the retinal layer changes from a new perspective in RP patients, which suggests that EZ and GCIPLT obtained by GCA combined with OCT imaging are the direct and valid indicators to diagnosis and predict the pathological process of RP. PMID:28033301

Influence of Clinical Factors and Magnification Correction on Normal Thickness Profiles of Macular Retinal Layers Using Optical Coherence Tomography.

PubMed

Higashide, Tomomi; Ohkubo, Shinji; Hangai, Masanori; Ito, Yasuki; Shimada, Noriaki; Ohno-Matsui, Kyoko; Terasaki, Hiroko; Sugiyama, Kazuhisa; Chew, Paul; Li, Kenneth K W; Yoshimura, Nagahisa

2016-01-01

To identify the factors which significantly contribute to the thickness variabilities in macular retinal layers measured by optical coherence tomography with or without magnification correction of analytical areas in normal subjects. The thickness of retinal layers {retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCLIPL), RNFL plus GCLIPL (ganglion cell complex, GCC), total retina, total retina minus GCC (outer retina)} were measured by macular scans (RS-3000, NIDEK) in 202 eyes of 202 normal Asian subjects aged 20 to 60 years. The analytical areas were defined by three concentric circles (1-, 3- and 6-mm nominal diameters) with or without magnification correction. For each layer thickness, a semipartial correlation (sr) was calculated for explanatory variables including age, gender, axial length, corneal curvature, and signal strength index. Outer retinal thickness was significantly thinner in females than in males (sr2, 0.07 to 0.13) regardless of analytical areas or magnification correction. Without magnification correction, axial length had a significant positive sr with RNFL (sr2, 0.12 to 0.33) and a negative sr with GCLIPL (sr2, 0.22 to 0.31), GCC (sr2, 0.03 to 0.17), total retina (sr2, 0.07 to 0.17) and outer retina (sr2, 0.16 to 0.29) in multiple analytical areas. The significant sr in RNFL, GCLIPL and GCC became mostly insignificant following magnification correction. The strong correlation between the thickness of inner retinal layers and axial length appeared to result from magnification effects. Outer retinal thickness may differ by gender and axial length independently of magnification correction.

Influence of Clinical Factors and Magnification Correction on Normal Thickness Profiles of Macular Retinal Layers Using Optical Coherence Tomography

PubMed Central

Higashide, Tomomi; Ohkubo, Shinji; Hangai, Masanori; Ito, Yasuki; Shimada, Noriaki; Ohno-Matsui, Kyoko; Terasaki, Hiroko; Sugiyama, Kazuhisa; Chew, Paul; Li, Kenneth K. W.; Yoshimura, Nagahisa

2016-01-01

Purpose To identify the factors which significantly contribute to the thickness variabilities in macular retinal layers measured by optical coherence tomography with or without magnification correction of analytical areas in normal subjects. Methods The thickness of retinal layers {retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCLIPL), RNFL plus GCLIPL (ganglion cell complex, GCC), total retina, total retina minus GCC (outer retina)} were measured by macular scans (RS-3000, NIDEK) in 202 eyes of 202 normal Asian subjects aged 20 to 60 years. The analytical areas were defined by three concentric circles (1-, 3- and 6-mm nominal diameters) with or without magnification correction. For each layer thickness, a semipartial correlation (sr) was calculated for explanatory variables including age, gender, axial length, corneal curvature, and signal strength index. Results Outer retinal thickness was significantly thinner in females than in males (sr2, 0.07 to 0.13) regardless of analytical areas or magnification correction. Without magnification correction, axial length had a significant positive sr with RNFL (sr2, 0.12 to 0.33) and a negative sr with GCLIPL (sr2, 0.22 to 0.31), GCC (sr2, 0.03 to 0.17), total retina (sr2, 0.07 to 0.17) and outer retina (sr2, 0.16 to 0.29) in multiple analytical areas. The significant sr in RNFL, GCLIPL and GCC became mostly insignificant following magnification correction. Conclusions The strong correlation between the thickness of inner retinal layers and axial length appeared to result from magnification effects. Outer retinal thickness may differ by gender and axial length independently of magnification correction. PMID:26814541

Lack of early pattern stimulation prevents normal development of the alpha (Y) retinal ganglion cell population in the cat.

PubMed

Burnat, Kalina; Van Der Gucht, Estelle; Waleszczyk, Wioletta J; Kossut, Malgorzata; Arckens, Lutgarde

2012-08-01

Binocular deprivation of pattern vision (BD) early in life permanently impairs global motion perception. With the SMI-32 antibody against neurofilament protein (NFP) as a marker of the motion-sensitive Y-cell pathway (Van der Gucht et al. [2001] Cereb. Cortex 17:2805-2819), we analyzed the impact of early BD on the retinal circuitry in adult, perceptually characterized cats (Burnat et al. [2005] Neuroreport 16:751-754). In controls, large retinal ganglion cells exhibited a strong NFP signal in the soma and in the proximal parts of the dendritic arbors. The NFP-immunoreactive dendrites typically branched into sublamina a of the inner plexiform layer (IPL), i.e., the OFF inner plexiform sublamina. In the retina of adult BD cats, however, most of the NFP-immunoreactive ganglion cell dendrites branched throughout the entire IPL. The NFP-immunoreactive cell bodies were less regularly distributed, often appeared in pairs, and had a significantly larger diameter compared with NFP-expressing cells in control retinas. These remarkable differences in the immunoreactivity pattern were typically observed in temporal retina. In conclusion, we show that the anatomical organization typical of premature Y-type retinal ganglion cells persists into adulthood even if normal visual experience follows for years upon an initial 6-month period of BD. Binocular pattern deprivation possibly induces a lifelong OFF functional domination, normally apparent only during development, putting early high-quality vision forward as a premise for proper ON-OFF pathway segregation. These new observations for pattern-deprived animals provide an anatomical basis for the well-described motion perception deficits in congenital cataract patients. Copyright © 2012 Wiley Periodicals, Inc.

Congenital giant plexiform neurofibroma with occipital calvarial dysplasia in association with meningoencephalocele in neurofibromatosis Type 1 and segmental neurofibromatosis: report of 2 cases.

PubMed

Dadlani, Ravi; Sadanand, Venkatraman; Ghosal, Nandita; Hegde, Alangar S

2013-11-01

Giant plexiform neurofibroma (GPNF) of the scalp is an extremely rare lesion reported in association with neurofibromatosis. Occipital location of GPNF is even more infrequent, especially in association with occipital dysplasia (OD). The authors report 2 pediatric cases of GPNF associated with OD. The first case had an associated meningoencephalocele, and the second had large vascular channels within the lesion and the dominant ipsilateral transverse sinus lying in the center of the calvarial defect. The authors present these 2 unusual cases with a review of literature and discuss the radiological findings, theories of etiopathogenesis of the OD, and management dilemmas.

ZIKA virus infection causes persistent chorioretinal lesions.

PubMed

Manangeeswaran, Mohanraj; Kielczewski, Jennifer L; Sen, H Nida; Xu, Biying C; Ireland, Derek D C; McWilliams, Ian L; Chan, Chi-Chao; Caspi, Rachel R; Verthelyi, Daniela

2018-05-25

Zika-infected patients can have eye involvement ranging from mild conjunctivitis to severe chorioretinal lesions, however the possible long-term sequelae of infection and timeline to recovery remain unknown. Here we describe the partial recovery of chorioretinal lesions in an immunocompetent patient diagnosed with bilateral posterior uveitis associated with Zika infection and show that some lesions resolved with focal atrophy evident as pigmentary changes on funduscopy. To better understand the progression of the lesions and correlate the changes in fundus imaging with local viral load, immune responses, and retinal damage, we developed a symptomatic mouse model of ocular Zika virus infection. Imaging of the fundus revealed multiple hypopigmentary patches indicative of chorioretinal degeneration as well as thinning of the retina that mirror the lesions in patients. Microscopically, the virus primarily infected the optic nerve, retinal ganglion cells, and inner nuclear layer cells, showing thinning of the outer plexiform layer. During acute infection, the eyes showed retinal layer disorganization, retinitis, vitritis, and focal choroiditis, with mild cellular infiltration and increased expression of tumor necrosis factor, interferon-γ, granzyme B, and perforin. Focal areas of gliosis and retinal degeneration persisted 60 dpi. The model recapitulates features of ZIKA infections in patients and should help elucidate the mechanisms underlying the damage to the eyes and aid in the development of effective therapeutics.

The phylogenomic roots of modern biochemistry: origins of proteins, cofactors and protein biosynthesis.

PubMed

Caetano-Anollés, Gustavo; Kim, Kyung Mo; Caetano-Anollés, Derek

2012-02-01

The complexity of modern biochemistry developed gradually on early Earth as new molecules and structures populated the emerging cellular systems. Here, we generate a historical account of the gradual discovery of primordial proteins, cofactors, and molecular functions using phylogenomic information in the sequence of 420 genomes. We focus on structural and functional annotations of the 54 most ancient protein domains. We show how primordial functions are linked to folded structures and how their interaction with cofactors expanded the functional repertoire. We also reveal protocell membranes played a crucial role in early protein evolution and show translation started with RNA and thioester cofactor-mediated aminoacylation. Our findings allow elaboration of an evolutionary model of early biochemistry that is firmly grounded in phylogenomic information and biochemical, biophysical, and structural knowledge. The model describes how primordial α-helical bundles stabilized membranes, how these were decorated by layered arrangements of β-sheets and α-helices, and how these arrangements became globular. Ancient forms of aminoacyl-tRNA synthetase (aaRS) catalytic domains and ancient non-ribosomal protein synthetase (NRPS) modules gave rise to primordial protein synthesis and the ability to generate a code for specificity in their active sites. These structures diversified producing cofactor-binding molecular switches and barrel structures. Accretion of domains and molecules gave rise to modern aaRSs, NRPS, and ribosomal ensembles, first organized around novel emerging cofactors (tRNA and carrier proteins) and then more complex cofactor structures (rRNA). The model explains how the generation of protein structures acted as scaffold for nucleic acids and resulted in crystallization of modern translation.

Enhanced depth imaging optical coherence tomography of choroidal metastasis in 14 eyes.

PubMed

Al-Dahmash, Saad A; Shields, Carol L; Kaliki, Swathi; Johnson, Timothy; Shields, Jerry A

2014-08-01

To describe the imaging features of choroidal metastasis using enhanced depth imaging optical coherence tomography (EDI-OCT). This retrospective observational case series included 31 eyes with choroidal metastasis. Spectral domain EDI-OCT was performed using Heidelberg Spectralis HRA + OCT. The main outcome measures were imaging features by EDI-OCT. Of 31 eyes with choroidal metastasis imaged with EDI-OCT, 14 (45%) eyes displayed image detail suitable for study. The metastasis originated from carcinoma of the breast (n = 7, 50%), lung (n = 5, 36%), pancreas (n = 1, 7%), and thyroid gland (n = 1, 7%). The mean tumor basal diameter was 6.4 mm, and mean thickness was 2.3 mm by B-scan ultrasonography. The tumor location was submacular in 6 (43%) eyes and extramacular in 8 (57%) eyes. By EDI-OCT, the mean tumor thickness was 987 μm. The most salient EDI-OCT features of the metastasis included anterior compression/obliteration of the overlying choriocapillaris (n = 13, 93%), an irregular (lumpy bumpy) anterior contour (n = 9, 64%), and posterior shadowing (n = 12, 86%). Overlying retinal pigment epithelial abnormalities were noted (n = 11, 78%). Outer retinal features included structural loss of the interdigitation of the cone outer segment tips (n = 9, 64%), the ellipsoid portion of photoreceptors (n = 8, 57%), external limiting membrane (n = 4, 29%), outer nuclear layer (n = 1, 7%), and outer plexiform layer (n = 1, 7%). The inner retinal layers (inner nuclear layer to nerve fiber layer) were normal. Subretinal fluid (n = 11, 79%), subretinal lipofuscin pigment (n = 1, 7%), and intraretinal edema (n = 2, 14%) were identified. The EDI-OCT of choroidal metastasis shows a characteristic lumpy bumpy anterior tumor surface and outer retinal layer disruption with preservation of inner retinal layers.

A model for the origin of photosynthesis--III. The ultraviolet photochemistry of uroporphyrinogen

NASA Technical Reports Server (NTRS)

Mercer-Smith, J. A.; Raudino, A.; Mauzerall, D. C.

1985-01-01

The photochemical ramifications of the high ultraviolet flux on the primordial earth prior to the formation of the ozone layer have been considered in a study of the ultraviolet photochemistry of uroporphyrinogen (urohexahydroporphyrin), a colorless compound which absorbs strongly at wavelengths less than 220 nanometers. Urohexahydroporphyrin was investigated since it is the first macrocycle formed on the biosynthetic pathway of chlorophyll and can be used to test the hypothesis that the biosynthetic pathway to chlorophyll recapitulates the evolutionary history of photosynthesis. When urohexahydroporphyrin is illuminated in aqueous anaerobic solution, hydrogen gas is produced. More hydrogen gas is produced in the presence of a colloidal platinum catalyst. The products of the photooxidation of urohexahydroporphyrin are urotetrahydroporphyrin (uroporphomethene) and uroporphyrin. This research shows how the oxidation of uroporphyrinogen to uroporphyrin, the first biogenetic porphyrin, could have occurred anaerobically and abiotically on the primordial earth.

Modeling intrinsic electrophysiology of AII amacrine cells: preliminary results.

PubMed

Apollo, Nick; Grayden, David B; Burkitt, Anthony N; Meffin, Hamish; Kameneva, Tatiana

2013-01-01

In patients who have lost their photoreceptors due to retinal degenerative diseases, it is possible to restore rudimentary vision by electrically stimulating surviving neurons. AII amacrine cells, which reside in the inner plexiform layer, split the signal from rod bipolar cells into ON and OFF cone pathways. As a result, it is of interest to develop a computational model to aid in the understanding of how these cells respond to the electrical stimulation delivered by a prosthetic implant. The aim of this work is to develop and constrain parameters in a single-compartment model of an AII amacrine cell using data from whole-cell patch clamp recordings. This model will be used to explore responses of AII amacrine cells to electrical stimulation. Single-compartment Hodgkin-Huxley-type neural models are simulated in the NEURON environment. Simulations showed successful reproduction of the potassium currentvoltage relationship and some of the spiking properties observed in vitro.

Investigation of changes in fractal dimension from layered retinal structures of healthy and diabetic eyes with optical coherence tomography

NASA Astrophysics Data System (ADS)

Gao, Wei; Zakharov, Valery P.; Myakinin, Oleg O.; Bratchenko, Ivan A.; Artemyev, Dmitry N.; Kornilin, Dmitry V.

2015-07-01

Optical coherence tomography (OCT) is usually employed for the measurement of retinal thickness characterizing the structural changes of tissue. However, fractal dimension (FD) could also character the structural changes of tissue. Therefore, fractal dimension changes may provide further information regarding cellular layers and early damage in ocular diseases. We investigated the possibility of OCT in detecting changes in fractal dimension from layered retinal structures. OCT images were obtained from diabetic patients without retinopathy (DM, n = 38 eyes) or mild diabetic retinopathy (MDR, n = 43 eyes) and normal healthy subjects (Controls, n = 74 eyes). Fractal dimension was calculated using the differentiate box counting methodology. We evaluated the usefulness of quantifying fractal dimension of layered structures in the detection of retinal damage. Generalized estimating equations considering within-subject intereye relations were used to test for differences between the groups. A modified p value of <0.001 was considered statistically significant. Receiver operating characteristic (ROC) curves were constructed to describe the ability of fractal dimension to discriminate between the eyes of DM, MDR and healthy eyes. Significant decreases of fractal dimension were observed in all layers in the MDR eyes compared with controls except in the inner nuclear layer (INL). Significant decreases of fractal dimension were also observed in all layers in the MDR eyes compared with DM eyes. The highest area under receiver operating characteristic curve (AUROC) values estimated for fractal dimension were observed for the outer plexiform layer (OPL) and outer segment photoreceptors (OS) when comparing MDR eyes with controls. The highest AUROC value estimated for fractal dimension were also observed for the retinal nerve fiber layer (RNFL) and OS when comparing MDR eyes with DM eyes. Our results suggest that fractal dimension of the intraretinal layers may provide useful information to differentiate pathological from healthy eyes. Further research is warranted to determine how this approach may be used to improve diagnosis of early retinal neurodegeneration.

The anatomy of the rat eye with oxygen-induced retinopathy.

PubMed

Akula, James D; Favazza, Tara L; Mocko, Julie A; Benador, Ilan Y; Asturias, Ana L; Kleinman, Michael S; Hansen, Ronald M; Fulton, Anne B

2010-02-01

Prior studies have documented the intertwined developmental courses of retinal blood vessel tortuosity (in fundus photographs) and retinal dysfunction (in electroretinographs) in Sprague-Dawley rat models of retinopathy of prematurity (ROP). Two such models, the "50/10 model" and the "75 model," are named after the oxygen regimens used to induce retinopathy and are characterized by distinct neurovascular courses that span a range of disease severity. In this study of 50/10 and 75 model rats, retinal flatmounts were used to study the full vasculature at postnatal day (P) 15, P19 and P30. In addition, the layers of the neural retina were measured in toluidine blue-stained cross sections. Finally, gross anatomic features of the eye, including axial length, retinal surface area, and the ratio of anterior to posterior axial-lengths were evaluated. Both clock hours of neovascularization (NV) and percent avascular retina (AR) peaked at P19 and resolved by P30. Through P19, NV was found in every 50/10 model rat, but in only 60% of 75 model rats. AR was positively related to NV. All inner layers of the retina (outer plexiform layer through ganglion cell layer) were attenuated in 50/10 model rats but, in the 75 model, no layer differed significantly from that in controls. The eyes in both ROP models were smaller than those of age-matched controls. The ratio of anterior to posterior axial-lengths ranged from 0.45 in controls through 0.37 in the 75 model to 0.32 in the 50/10 model. Thus, eye growth is altered in these rat models of ROP.

Aldose reductase mediates retinal microglia activation

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

Chang, Kun-Che; Shieh, Biehuoy; Petrash, J. Mark, E-mail: mark.petrash@ucdenver.edu

Retinal microglia (RMG) are one of the major immune cells in charge of surveillance of inflammatory responses in the eye. In the absence of an inflammatory stimulus, RMG reside predominately in the ganglion layer and inner or outer plexiform layers. However, under stress RMG become activated and migrate into the inner nuclear layer (INL) or outer nuclear layer (ONL). Activated RMG in cell culture secrete pro-inflammatory cytokines in a manner sensitive to downregulation by aldose reductase inhibitors. In this study, we utilized CX3CR1{sup GFP} mice carrying AR mutant alleles to evaluate the role of AR on RMG activation and migrationmore » in vivo. When tested on an AR{sup WT} background, IP injection of LPS induced RMG activation and migration into the INL and ONL. However, this phenomenon was largely prevented by AR inhibitors or in AR null mice, or was exacerbated in transgenic mice that over-express AR. LPS-induced increases in ocular levels of TNF-α and CX3CL-1 in WT mice were substantially lower in AR null mice or were reduced by AR inhibitor treatment. These studies demonstrate that AR expression in RMG may contribute to the proinflammatory phenotypes common to various eye diseases such as uveitis and diabetic retinopathy. - Highlights: • AR inhibition prevents retinal microglial activation. • Endotoxin-induced ocular cytokine production is reduced in AR null mice. • Overexpression of AR spontaneously induces retinal microglial activation.« less

Retinal Ganglion Cell Layer Thickness and Local Visual Field Sensitivity in Glaucoma

PubMed Central

Raza, Ali S.; Cho, Jungsuk; de Moraes, Carlos G. V.; Wang, Min; Zhang, Xian; Kardon, Randy H.; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

2015-01-01

Objective To compare loss in sensitivity measured using standard automated perimetry (SAP) with local retinal ganglion cell layer (RGC) thickness measured using frequency-domain optical coherence tomography in the macula of patients with glaucoma. Methods To compare corresponding locations of RGC thickness with total deviation (TD) of 10-2 SAP for 14 patients with glaucoma and 19 controls, an experienced operator hand-corrected automatic segmentation of the combined RGC and inner plexiform layer (RGC + IPL) of 128 horizontal B-scans. To account for displacement of the RGC bodies around the fovea, the location of the SAP test points was adjusted to correspond to the location of the RGC bodies rather than to the photoreceptors, based on published histological findings. For analysis, RGC + IPL thickness vs SAP (TD) data were grouped into 5 eccentricities, from 3.4° to 9.7° radius on the retina with respect to the fovea. Results The RGC + IPL thickness correlated well with SAP loss within approximately 7.2° of the fovea (Spearman ρ = 0.71–0.74). Agreement was worse (0.53–0.65) beyond 7.2°, where the normal RGC layer is relatively thin. A linear model relating RGC + IPL thickness to linear SAP loss provided a reasonable fit for eccentricities within 7.2°. Conclusion In the central 7.2°, local RGC + IPL thickness correlated well with local sensitivity loss in glaucoma when the data were adjusted for RGC displacement. PMID:22159673

The Cosmochemistry of Pluto: A Primordial Origin of Volatiles?

NASA Astrophysics Data System (ADS)

Glein, C. R.; Waite, J. H., Jr.

2017-12-01

Pluto is a wonderland of volatiles. Nitrogen, methane, and carbon monoxide are the principal volatiles that maintain its tenuous atmosphere, and they have also created a mesmerizing landscape of icy geological features, including Pluto's iconic "heart". Recent data, particularly those returned by the New Horizons mission [1-3], allow us to begin testing hypotheses for the cosmochemical origins of these world-shaping species on Pluto. Here, we investigate if Pluto's volatiles could have been accreted in its building blocks. We take both bottom-up and top-down approaches in testing this hypothesis in terms of mass balance. We estimate Pluto's primordial inventory of volatiles by scaling a range of cometary abundances up to the ice mass fraction of Pluto. We also make estimates of the present and lost inventories of volatiles based on surface observations and interpretations, as well as different scenarios of atmospheric photochemistry and escape. We find that, if primordial Pluto resembled a giant comet with respect to volatile abundances, then the initial volatile inventory would have been sufficient to account for the estimated present and lost inventories. This consistency supports a primordial origin for Pluto's volatiles. However, the observed ratio of CO/N2 in Pluto's atmosphere [4] is several orders of magnitude lower than the nominal cometary value. We are currently using phase equilibrium and rate models to explore if volatile layering in Sputnik Planitia, or the destruction of CO in a past or present subsurface ocean of liquid water could explain the apparent depletion of CO on Pluto. References: [1] Moore et al. (2016) Science 351, 1284. [2] Grundy et al. (2016) Science 351, aad9189. [3] Gladstone et al. (2016) Science 351, aad8866. [4] Lellouch et al. (2017) Icarus 286, 289.

Synergistic Interplay between Curcumin and Polyphenol-Rich Foods in the Mediterranean Diet: Therapeutic Prospects for Neurofibromatosis 1 Patients.

PubMed

Esposito, Teresa; Schettino, Carla; Polverino, Paola; Allocca, Salvatore; Adelfi, Laura; D'Amico, Alessandra; Capaldo, Guglielmo; Varriale, Bruno; Di Salle, Anna; Peluso, Gianfranco; Sorrentino, Giuseppe; Lus, Giacomo; Sampaolo, Simone; Di Iorio, Giuseppe; Melone, Mariarosa Anna Beatrice

2017-07-21

Neurofibromas are the hallmark lesions in Neurofibromatosis 1 (NF1); these tumors are classified as cutaneous, subcutaneous and plexiform. In contrast to cutaneous and subcutaneous neurofibromas, plexiform neurofibromas can grow quickly and progress to malignancy. Curcumin, a turmeric-derived polyphenol, has been shown to interact with several molecular targets implicated in carcinogenesis. Here, we describe the impact of different dietary patterns, namely Mediterranean diet (MedDiet) compared to the Western diet (WesDiet), both with or without curcumin, on NF1 patients' health. After six months, patients adopting a traditional MedDiet enriched with 1200 mg curcumin per day (MedDietCurcumin) presented a significant reduction in the number and volume of cutaneous neurofibromas; these results were confirmed in subsequent evaluations. Notably, in one patient, a large cranial plexiform neurofibroma exhibited a reduction in volume (28%) confirmed by Magnetic Resonance Imaging. Conversely, neither unenriched MedDiet nor WesDiet enriched with curcumin exhibited any significant positive effect. We hypothesize that the combination of a polyphenol-rich Mediterranean diet and curcumin was responsible for the beneficial effect observed on NF1. This is, to the best of our knowledge, the first experience with curcumin supplementation in NF1 patients. Our report suggests that an integrated nutritional approach may effectively aid in the management of NF1.

Region-specific ischemia, neovascularization and macular oedema in treatment-naïve proliferative diabetic retinopathy.

PubMed

Lange, Jason; Hadziahmetovic, Majda; Zhang, Jingfa; Li, Weiye

2018-02-07

Region-specific pathology in proliferative diabetic retinopathy enhances our understanding and management of this disease. To investigate non-perfusion, neovascularization and macular oedema. A cross-sectional, observational, non-randomized study. Consecutive 43 eyes of 27 treatment-naïve patients. Ultra-widefield fluorescein angiography for studying specific zones, that is, far-peripheral zone, mid-peripheral zone and central retina (cr), and spectral-domain optical coherence tomography for analysing thickness of macular layers. Non-perfusion index (NPI) and neovascularization index (NVI) in different zones, thickness of cr, retinal nerve fibre layer, ganglion cell layer (GCL), inner nuclear layer (INL) and outer plexiform layer in parafoveal regions. The NPI of far-periphery and NVI of mid-periphery were the highest by one-way analysis of variance testing. Ischemic retina defined as high NPI in far-periphery was significantly related to macular oedema via a binary classification approach (P < 0.05). The ischemic retina was correlated with a decreased thickness of both retinal nerve fibre and GCL (P < 0.05); macular oedema was correlated with increased INL thickness (P < 0.0001). The region-specific correlation of NPI of far-periphery and NVI of mid-periphery, but not with central retinal thickness, suggests different pathogeneses of neovascularization and macular oedema. Retinal nerve fibre layer and GCL, both biomarkers of diabetic retinal neuronopathy, are associated with retinal ischemia, but not with macular oedema, suggesting that diabetic microangiopathy and neuronopathy possess distinct pathogenic pathways. The strong correlation between macular oedema and INL indicates that intracellular oedema is a determining factor of diabetic macular oedema. © 2018 Royal Australian and New Zealand College of Ophthalmologists.

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.

Ultrahigh resolution optical coherence tomography for quantitative topographic mapping of retinal and intraretinal architectural morphology

NASA Astrophysics Data System (ADS)

Ko, Tony H.; Hartl, Ingmar; Drexler, Wolfgang; Ghanta, Ravi K.; Fujimoto, James G.

2002-06-01

Quantitative, three-dimensional mapping of retinal architectural morphology was achieved using an ultrahigh resolution ophthalmic OCT system. This OCT system utilizes a broad bandwidth titanium-sapphire laser light source generating bandwidths of up to 300 nm near 800 nm center wavelength. The system enables real-time cross-sectional imaging of the retina with ~3 micrometers axial resolution. The macula and the papillomacular axis of a normal human subject were systematically mapped using a series of linear scans. Edge detection and segmentation algorithms were developed to quantify retinal and intraretinal thicknesses. Topographic mapping of the total retinal thickness and the total ganglion cell/inner plexiform layer thickness was achieved around the macula. A topographic mapping quantifying the progressive thickening of the nerve fiber layer (NFL) nasally approaching the optic disk was also demonstrated. The ability to create three-dimensional topographic mapping of retinal architectural morphology at ~3 micrometers axial resolution will be relevant for the diagnosis of many retinal diseases. The topographic quantification of these structures can serve as a powerful tool for developing algorithms and clinical scanning protocols for the screening and staging of ophthalmic diseases such as glaucoma.

Malignant ameloblastic fibro-odontoma in a dog.

PubMed

Ueki, H; Sumi, A; Takaishi, H; Ito, H; Oyamada, T; Yoshikawa, H

2004-03-01

An 11-year-old male Collie was presented with a swelling of the face caused by tumor masses arising from the gingiva. Postmortem examination revealed metastases to the lymph nodes, lung, liver, and orbital cavity. Histologically, the tumor represented a combination of fibrosarcomatous proliferation, pulpal mesenchyme, and undifferentiated odontogenic epithelium, with a follicular or plexiform growth pattern. In addition, the follicular areas of the tumor showed a biphasic character, and there were numerous apoptotic cells in plexiform areas. Furthermore, acidophilic material resembling dysplastic dentine or enamel matrix was observed in the metastatic lesion in the lung. Based on the histological characters, the present case was diagnosed as malignant ameloblastic fibro-odontoma. This study is the first known description of a possible malignant ameloblastic fibro-odontoma in a dog with metastasis to distant organs.

Tumor necrosis factor and its receptors in the neuroretina and retinal vasculature after ischemia-reperfusion injury in the pig retina

PubMed Central

Gesslein, Bodil; Håkansson, Gisela; Gustafsson, Lotta; Ekström, Per

2010-01-01

Purpose Numerous studies have been performed aimed at limiting the extent of retinal injury after ischemia, but there is still no effective pharmacological treatment available. The aim of the present study was to examine the role of tumor necrosis factor (TNF)α and its receptors (TNF-R1 and TNF-R2), especially considering the neuroretina and the retinal vasculature since the retinal blood vessels are key organs in circulatory failure. Methods Retinal ischemia was induced in pigs by elevating the intraocular pressure to 80 mmHg in one eye, while the other eye served as a control (sham-operated). One hour of ischemia was followed by 5 or 12 h of reperfusion. Retinal circulation was examined in vivo by fundus imaging and fluorescein angiography. TNF-α levels were measured in the vitreous using an angiogenesis antibody array test. The presence and amounts of TNF-α, TNF-R1, and TNF-R2 were investigated in the neuroretina and in the retinal blood vessels, using immunofluorescence staining and real-time PCR techniques. Results Fundus imaging showed obstructed blood flow when ischemia was induced, and reperfusion was clearly visualized using fluorescein angiography. Ischemia resulted in elevated levels of TNF-α protein in the vitreous and TNF-α mRNA in the neuroretina. TNF-α immunofluorescence staining was localized to the Müller cells and the outer plexiform layer of the neuroretina. The expression of TNF-R1 and TNF-R2 mRNA was increased in both the neuroretina and retinal arteries following ischemia-reperfusion. Immunofluorescence double staining for TNF-R1 and either smooth muscle actin or 4',6-diamidino-2-phenylindole (DAPI) indicated expression in the cell membranes of the vascular smooth muscle cells. Double staining with TNF-R1 and calbindin showed localization to the horizontal cells in the outer plexiform layer of the neuroretina. Conclusions Retinal ischemia results in increased expression of TNF-α and its receptors (TNF-R1 and TNF-R2). Cellular signaling pathways involving TNF may be important in the development of retinal injury following ischemia and thus an interesting target for future development of pharmacological therapeutics. PMID:21152396

Patterns of Progressive Ganglion Cell-Inner Plexiform Layer Thinning in Glaucoma Detected by OCT.

PubMed

Shin, Joong Won; Sung, Kyung Rim; Park, Sun-Won

2018-04-25

To investigate the spatial characteristics and patterns of progressive macular ganglion cell-inner plexiform layer (GCIPL) thinning in glaucomatous eyes assessed by OCT Guided Progression Analysis (GPA). Longitudinal, retrospective, observational study. Two hundred ninety-two eyes of 192 patients with primary open-angle glaucoma with a mean follow-up of 6.0 years (range, 3.2-8.1 years) were included. Macular GCIPL imaging and visual field (VF) examination were performed at 6-month intervals for 3 years or more. Progressive GCIPL thinning was evaluated by a Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) GPA device. Spatial characteristics of progressive GCIPL thinning were assessed by the GCIPL thickness change map. The pattern of progressive GCIPL thinning was evaluated by comparing the baseline GCIPL thickness deviation map and the final GCIPL thickness change map. Visual field progression was determined by Early Manifest Glaucoma Trial criteria and linear regression of the VF index. Spatial characteristics and patterns of progressive GCIPL thinning. Seventy-two eyes of 62 participants (24.7% [72/292]) showed progressive GCIPL thinning in the GCIPL thickness change map. Progressive GCIPL thinning was detected most frequently (25.0%) at 2.08 mm from the fovea, and it extended in an arcuate shape in the inferotemporal region (250°-339°). Compared with the baseline GCIPL defects, the progressive GCIPL thinning extended toward the fovea and optic disc. The most common pattern of progressive GCIPL thinning was widening of GCIPL defects (42 eyes [58.3%]), followed by deepening of GCIPL defects (19 eyes [26.4%]) and newly developed GCIPL defects (15 eyes [20.8%]). Visual field progression was accompanied by progressive GCIPL thinning in 41 of 72 eyes (56.9%). Progressive GCIPL thinning preceded (61.0% [25/41]) or occurred concomitantly with (21.9% [9/41]) VF progression. The use of OCT GPA maps offers an effective approach to evaluate the topographic patterns of progressive GCIPL thinning in glaucomatous eyes. Progression of GCIPL thinning occurred before apparent progression on standard automated perimetry in most glaucomatous eyes. Understanding specific patterns and sequences of macular damage may provide important insights in the monitoring of glaucomatous progression. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Neurodegeneration in diabetic retinopathy: Potential for novel therapies.

PubMed

Barber, Alistair J; Baccouche, Basma

2017-10-01

The complex pathology of diabetic retinopathy (DR) affects both vascular and neural tissue. The characteristics of neurodegeneration are well-described in animal models but have more recently been confirmed in the clinical setting, mostly by using non-invasive imaging approaches such as spectral domain optical coherence tomography (SD-OCT). The most frequent observations report loss of tissue in the nerve fiber layer and inner plexiform layer, confirming earlier findings from animal models. In several cases the reduction in inner retinal layers is reported in patients with little evidence of vascular lesions or macular edema, suggesting that degenerative loss of neural tissue in the inner retina can occur after relatively short durations of diabetes. Animal studies also suggest that neurodegeneration leading to retinal thinning is not limited to cell death and tissue loss but also includes changes in neuronal morphology, reduced synaptic protein expression and alterations in neurotransmission, including changes in expression of neurotransmitter receptors as well as neurotransmitter release, reuptake and metabolism. The concept of neurodegeneration as an early component of DR introduces the possibility to explore alternative therapies to prevent the onset of vision loss, including neuroprotective therapies and drugs targeting individual neurotransmitter systems, as well as more general neuroprotective approaches to preserve the integrity of the neural retina. In this review we consider some of the evidence for progressive retinal neurodegeneration in diabetes, and explore potential neuroprotective therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

A study regarding the stability of the primordial crust of asteroid Ceres

NASA Astrophysics Data System (ADS)

Formisano, Michelangelo; Federico, Costanzo; De Sanctis, Maria Cristina; De Angelis, Simone

2016-04-01

Ceres is a particular object of the solar system, since it is a "transition body" between the icy satellites of the outer solar system and the rocky bodies of the inner part. Probably it is differentiated [1,2], i.e. it has a core made of "rock" (silicates) with a weak presence of metals, a large icy mantle and a rocky crust. In particular, it has been proposed the existence on the surface of the ammoniated phyllosilicates, compatible with an outer solar system origin [3]. Also water in clay minerals, brucite, and iron-rich serpentine have been proposed to exist on the surface [4]. Ice directly on the surface regolith seems to be very unstable: numerical simulations of [5] indicate that it can last for very few orbits. A crust made of a mixture of ice and rock is potentially unstable. In the solar system, for example, Callisto has such a crust but its surface temperature is below the critical temperature for the Rayleigh-Taylor instability [6]: this seems not to be the case of Ceres. In this work, we verify the stability of the primordial crust, by assuming a certain initial composition (ice and rock) and thickness. We assume a post-differentiation Ceres, made of three layers (rocky core, icy mantle and crust). The key role is played by the viscosity of the layers, which influenced the survival or not of the primordial crust. We applied the method of the parametrized thermal convection widely diffused in literature. [1] McCord, T.B. and Sotin, C., 2005, JGR 110 [2] Castillo-Rogez, J.C., and McCord, T.B., 2010, Icarus 205, 443-459 [3] De Sanctis, M.C. et al., 2015, doi:10.1038/nature16172 [4] Rivkin, A.S., et al., 2014, Space Sci Rev, 95-116, 163, doi 10.1007/s11214-010-9677-4 [5] Formisano, M., et al., 2016, MRAS 455, 1892-1904 [6] Shoji, D. and Kurita, K., 2014, doi:10.1002/2014JE004695.

Morphological Diversity of the Rod Spherule: A Study of Serially Reconstructed Electron Micrographs

PubMed Central

Li, Shuai; Mitchell, Joe; Briggs, Deidrie J.; Young, Jaime K.; Long, Samuel S.; Fuerst, Peter G.

2016-01-01

Purpose Rod spherules are the site of the first synaptic contact in the retina’s rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM) and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon. Retraction of the rod axon and spherule is often observed in disease processes and aging, and the retracted rod spherule superficially resembles rod spherules lacking an axon. We hypothesized that retracted spherules take on an axonless spherule morphology, which may be easier to maintain in a diseased state. To test our hypothesis, we quantified the spatial organization and subcellular structures of rod spherules with and without axons. We then compared them to the retracted spherules in a disease model, mice that overexpress Dscam (Down syndrome cell adhesion molecule), to gain a better understanding of the rod synapse in health and disease. Methods We reconstructed serial EM images of wild type and DscamGoF (gain of function) rod spherules at a resolution of 7 nm in the X-Y axis and 60 nm in the Z axis. Rod spherules with and without axons, and retracted spherules in the DscamGoF retina, were reconstructed. The rod spherule intracellular organelles, the invaginating dendrites of rod bipolar cells and horizontal cell axon tips were also reconstructed for statistical analysis. Results Stereotypical rod (R1) spherules occupy the outer two-thirds of the outer plexiform layer (OPL), where they present as spherical terminals with large mitochondria. This spherule group is highly uniform and composed more than 90% of the rod spherule population. Rod spherules lacking an axon (R2) were also described and characterized. This rod spherule group consists of a specific spatial organization that is strictly located at the apical OPL-facing layer of the Outer Nuclear Layer (ONL). The R2 spherule displays a large bowl-shaped synaptic terminal that hugs the rod soma. Retracted spherules in the DscamGoF retina were also reconstructed to test if they are structurally similar to R2 spherules. The misplaced rod spherules in DscamGoF have a gross morphology that is similar to R2 spherules but have significant disruption in internal synapse organization. Conclusion We described a morphological diversity within Mus musculus rod spherules. This diversity is correlated with rod location in the ONL and contributes to the intracellular differences within spherules. Analysis of the DscamGoF retina indicated that their R2 spherules are not significantly different than wild type R2 spherules, but that their retracted rod spherules have abnormal synaptic organization. PMID:26930660

Morphological Diversity of the Rod Spherule: A Study of Serially Reconstructed Electron Micrographs.

PubMed

Li, Shuai; Mitchell, Joe; Briggs, Deidrie J; Young, Jaime K; Long, Samuel S; Fuerst, Peter G

2016-01-01

Rod spherules are the site of the first synaptic contact in the retina's rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM) and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon. Retraction of the rod axon and spherule is often observed in disease processes and aging, and the retracted rod spherule superficially resembles rod spherules lacking an axon. We hypothesized that retracted spherules take on an axonless spherule morphology, which may be easier to maintain in a diseased state. To test our hypothesis, we quantified the spatial organization and subcellular structures of rod spherules with and without axons. We then compared them to the retracted spherules in a disease model, mice that overexpress Dscam (Down syndrome cell adhesion molecule), to gain a better understanding of the rod synapse in health and disease. We reconstructed serial EM images of wild type and DscamGoF (gain of function) rod spherules at a resolution of 7 nm in the X-Y axis and 60 nm in the Z axis. Rod spherules with and without axons, and retracted spherules in the DscamGoF retina, were reconstructed. The rod spherule intracellular organelles, the invaginating dendrites of rod bipolar cells and horizontal cell axon tips were also reconstructed for statistical analysis. Stereotypical rod (R1) spherules occupy the outer two-thirds of the outer plexiform layer (OPL), where they present as spherical terminals with large mitochondria. This spherule group is highly uniform and composed more than 90% of the rod spherule population. Rod spherules lacking an axon (R2) were also described and characterized. This rod spherule group consists of a specific spatial organization that is strictly located at the apical OPL-facing layer of the Outer Nuclear Layer (ONL). The R2 spherule displays a large bowl-shaped synaptic terminal that hugs the rod soma. Retracted spherules in the DscamGoF retina were also reconstructed to test if they are structurally similar to R2 spherules. The misplaced rod spherules in DscamGoF have a gross morphology that is similar to R2 spherules but have significant disruption in internal synapse organization. We described a morphological diversity within Mus musculus rod spherules. This diversity is correlated with rod location in the ONL and contributes to the intracellular differences within spherules. Analysis of the DscamGoF retina indicated that their R2 spherules are not significantly different than wild type R2 spherules, but that their retracted rod spherules have abnormal synaptic organization.

The problem of the origin of primordial germ cells (PGCs) in vertebrates: historical review and a possible solution.

PubMed

Pilato, Giovanni; D'Urso, Vera; Viglianisi, Fabio; Sammartano, Francesca; Sabella, Giorgio; Lisi, Oscar

2013-01-01

A concise review of the articles about the origin of primordial germ cells (PGCs) in vertebrates is provided. Differences among various taxa concerning the origin of PGCs, not easily understandable on the base of traditional knowledge, are pointed out. All those differences can be explained taking into consideration the recent “theory of the endoderm as secondary layer”. That theory allows us to understand that those differences are only apparent, being related to modifications of stages of the consequent embryogeny, overall, to a different amount of yolk in the egg. Eggs very rich in yolk became meroblastic, and the portion of primordial ectomesenchyme destined to give rise to a part of the mesoderm and the PGCs separates early from the part destined to give rise to the rest of the mesoderm and to the digestive endoderm in order to form the vitelline hypoblast lamina. To this lamina, in contrast to the traditional interpretation, a mesodermal, not endodermal, origin must be attributed. With the misunderstanding regarding the origin of this lamina clarified, all the differences about the origin of PGCs disappears. Furthermore, in taxa where PGCs were considered to be of endodermal origin, they too have a mesodermal origin. Considering that a mesodermal origin of PGCs has been demonstrated in all sponges and cnidarians, as well, a unique, mesodermal origin of germinal cells in all pluricellular animals results.

Cells of origin in the embryonic nerve roots for NF1-associated plexiform neurofibroma

PubMed Central

Chen, Zhiguo; Liu, Chiachi; Patel, Amish J.; Liao, Chung-Ping; Wang, Yong; Le, Lu Q.

2014-01-01

Summary Neurofibromatosis type 1 is a tumor-predisposing genetic disorder. Plexiform neurofibromas are common NF1 tumors carrying a risk of malignant transformation, which is typically fatal. Little is known about mechanisms mediating initiation and identity of specific cell-type that gives rise to neurofibromas. Using cell-lineage tracing, we identify a population of GAP43+ PLP+ precursors in embryonic nerve roots as the cells of origin for these tumors and report a non-germline model of neurofibroma for preclinical drug screening to identify effective therapies. The identity of tumor cell-of-origin and facility for isolation and expansion provides fertile ground for continued analysis to define intrinsic and extrinsic factors critical for neurofibromagenesis. It also provides unique approaches to develop therapies to prevent neurofibroma formation in NF1 patients. PMID:25446898

The origin and evolution of a differentiated Mimas

NASA Astrophysics Data System (ADS)

Neveu, M.; Rhoden, A. R.

2017-11-01

In stark contrast with its neighbor moon Enceladus, Mimas is surprisingly geologically quiet, despite an eccentric orbit and distance to Saturn prone to levels of tidal dissipation 30 times higher. While Mimas' lack of geological activity could be due to a stiff, frigid interior, libration data acquired using the Cassini spacecraft suggest that its interior is not homogeneous. Here, we present one-dimensional models of the thermal, structural, and orbital evolution of Mimas under two accretion scenarios: primordial, undifferentiated formation in the Saturnian sub-nebula, and late, layered formation from a debris ring created by the disruption of one or more previous moons. We find it difficult to reproduce a differentiated, eccentric Mimas under a primordial accretion scenario: either Mimas never differentiates, or the internal warming that leads to differentiation increases tidal dissipation, yielding runaway heating that produces a persistent ocean, thereby circularizing Mimas' orbit. Only if Mimas accretes very early (so that the decay of short-lived radionuclides initiates differentiation) but its rheology is not highly dissipative (in order to stop runaway tidal heating even if the eccentricity is not negligible) can the simulations match the observational constraints. Alternatively, a late, layered accretion scenario yields a present-day Mimas that matches observational constraints, independently of the magnitude of tidal dissipation. Consistent with previous findings, these models do not produce an ocean on Enceladus unless its orbital eccentricity is higher than today's value.

Staging of Macular Telangiectasia: Power-Doppler Optical Coherence Tomography and Macular Pigment Optical Density

PubMed Central

Chin, Eric K.; Kim, Dae Yu; Hunter, Allan A.; Pilli, Suman; Wilson, Machelle; Zawadzki, Robert J.; Werner, John S.; Park, Susanna S.

2013-01-01

Purpose. Two methods were used to study the stages of macular telangiectasia (MacTel): Power-Doppler optical coherence tomography (PD-OCT), which allows imaging of the retinal circulation in three dimensions, and macular pigment optical density (MPOD), which quantifies the distribution of macular carotenoids. Methods. Among 49 patients with MacTel identified, 12 eyes (6 patients) with MacTel and 7 age-matched control eyes (7 patients) were imaged with a custom-built Fourier-domain OCT instrument to acquire PD-OCT images. MPOD was measured using heterochromatic flicker photometry in 10 eyes (5 patients) with MacTel and compared with 44 age-matched control eyes (44 patients). Clinical staging of MacTel was based on best-corrected visual acuity, fundus biomicroscopy, fluorescein angiography, and OCT. Results. Stage 1 eyes (n = 2) had subtle punctate vascular signal confined to the inner portion of the outer plexiform layer (OPL) on PD-OCT. Stage 2 (n = 2) showed larger oblique vascular signal extending into deeper OPL. Stage 3 (n = 5) had disruption of outer retinal layers with abnormal vasculature extending into the outer nuclear layer. Stage 4 (n = 3) showed diffuse blurring of the retinal layers with vascular channels extending the full thickness of the retina. MPOD values in four eyes with stage 1 or 2 MacTel correlated well with age-matched controls. Six eyes with stage 3 or 4 MacTel had loss of MPOD especially at the fovea. Conclusions. PD-OCT shows penetration of the retinal capillaries into the deeper retinal layers in early stages of MacTel, with full thickness vascular proliferation in advanced disease. MPOD is commonly depleted but may appear normal in early stage MacTel. PMID:23716628

Comparison of Foveal, Macular, and Peripapillary Intraretinal Thicknesses Between Autism Spectrum Disorder and Neurotypical Subjects.

PubMed

García-Medina, José Javier; García-Piñero, María; Del-Río-Vellosillo, Mónica; Fares-Valdivia, Jesarán; Ragel-Hernández, Ana Belén; Martínez-Saura, Salvador; Cárcel-López, María Dolores; Zanon-Moreno, Vicente; Pinazo-Duran, María Dolores; Villegas-Pérez, María Paz

2017-11-01

To compare thicknesses of intraretinal layers segmented by spectral-domain optical coherence tomography (SD-OCT) between autism spectrum disorder (ASD) and neurotypical (NT) individuals. We performed 2 scans on 108 eyes from 54 participants (27 high-functioning ASD and 27 age- and sex-matched NT subjects): macular fast volume and peripapillary retinal nerve fiber layer (pRNFL). Macula was automatically segmented. The mean foveal and macular thickness of nine different layers and the thickness of nine pRNFL sectors were considered. Data from the right and left eyes were averaged for each participant. The results were compared between the ASD and NT groups. Associations between the Kaufman brief intelligence test (K-BIT), head circumference and SD-OCT results were also investigated in ASD individuals. ASD subjects showed greater foveal thickness at total retina, total inner retina, inner plexiform and inner nuclear layers, and greater macular thickness at total retina and total inner retina. Inferior, nasal inferior and temporal inferior sectors of pRNFL were also thicker in the ASD participants than in the controls (P < 0.05, unpaired t-test). Significant correlations were found between some K-BIT results and temporal inferior and inferior pRNFL thicknesses in the ASD group (P < 0.05, Spearman's rank correlation). No associations were seen between head circumference and OCT parameters. There are intraretinal thickenings at different locations in ASD subjects when compared to NT controls. This fact should be taken into account when interpreting SD-OCT examinations in ASD individuals. Plus, some pRNFL thicknesses present positive correlations with scores of cognitive status in ASD.

IPLaminator: an ImageJ plugin for automated binning and quantification of retinal lamination.

PubMed

Li, Shuai; Woodfin, Michael; Long, Seth S; Fuerst, Peter G

2016-01-16

Information in the brain is often segregated into spatially organized layers that reflect the function of the embedded circuits. This is perhaps best exemplified in the layering, or lamination, of the retinal inner plexiform layer (IPL). The neurites of the retinal ganglion, amacrine and bipolar cell subtypes that form synapses in the IPL are precisely organized in highly refined strata within the IPL. Studies focused on developmental organization and cell morphology often use this layered stratification to characterize cells and identify the function of genes in development of the retina. A current limitation to such analysis is the lack of standardized tools to quantitatively analyze this complex structure. Most previous work on neuron stratification in the IPL is qualitative and descriptive. In this study we report the development of an intuitive platform to rapidly and reproducibly assay IPL lamination. The novel ImageJ based software plugin we developed: IPLaminator, rapidly analyzes neurite stratification patterns in the retina and other neural tissues. A range of user options allows researchers to bin IPL stratification based on fixed points, such as the neurites of cholinergic amacrine cells, or to define a number of bins into which the IPL will be divided. Options to analyze tissues such as cortex were also added. Statistical analysis of the output then allows a quantitative value to be assigned to differences in laminar patterning observed in different models, genotypes or across developmental time. IPLaminator is an easy to use software application that will greatly speed and standardize quantification of neuron organization.

Retinal profile and structural differences between myopes and emmetropes

NASA Astrophysics Data System (ADS)

Clark, Christopher Anderson

Refractive development has been shown to be influenced by optical defocus in the eye and the interpretation of this signal appears to be localized in the retina. Optical defocus is not uniform across the retina and has been suggested as a potential cause of myopia development. Specifically hyperopic focus, i.e. focusing light behind the retina, may signal the eye to elongate, causing myopia. This non-uniform hyperopic signal appears to be due to the retinal shape. Ultimately, these signals are detected by the retina in an as yet undetermined manner. The purpose of this thesis is to examine the retinal profile using a novel method developed at Indiana University and then to examine retinal structural changes across the retina associated with myopia. Myopes exhibited more prolate retinas than hyperopes/emmetropes using the SD OCT. Using the SD OCT, this profile difference was detectable starting at 5 degrees from the fovea, which was closer than previously reported in the literature. These results agreed significantly with results found from peripheral refraction and peripheral axial length at 10 degrees. Overall, the total retina was thinner for myopes than hyperopes/emmetropes. It was also statistically significantly thinner for the Outer Nuclear Layer (ONL), Inner Nuclear Layer (INL) and Outer Plexiform Layer (OPL) but not for other retinal layers such as the Ganglion Layer. Thinning generally occurred outside of 5 degrees. The SD OCT method provided a nearly 10 fold increase in sensitivity which allowed for detection of profile changes closer to the fovea. The location of the retinal changes may be interesting as the layers that showed significant differences in thickness are also layers that contain cells believed to be associated with refractive development (amacrine, bipolar, and photoreceptor cells.) The reason for the retinal changes cannot be determined with this study, but possible theories include stretch due to axial elongation, neural remodeling due to blur, and/or direct influence on refractive development due to neural cell densities.

Analysis of Agreement of Retinal-Layer Thickness Measures Derived from the Segmentation of Horizontal and Vertical Spectralis OCT Macular Scans.

PubMed

Gonzalez Caldito, Natalia; Antony, Bhavna; He, Yufan; Lang, Andrew; Nguyen, James; Rothman, Alissa; Ogbuokiri, Esther; Avornu, Ama; Balcer, Laura; Frohman, Elliot; Frohman, Teresa C; Bhargava, Pavan; Prince, Jerry; Calabresi, Peter A; Saidha, Shiv

2018-03-01

Optical coherence tomography (OCT) is a reliable method used to quantify discrete layers of the retina. Spectralis OCT is a device used for this purpose. Spectralis OCT macular scan imaging acquisition can be obtained on either the horizontal or vertical plane. The vertical protocol has been proposed as favorable, due to postulated reduction in confound of Henle's fibers on segmentation-derived metrics. Yet, agreement of the segmentation measures of horizontal and vertical macular scans remains unexplored. Our aim was to determine this agreement. Horizontal and vertical macular scans on Spectralis OCT were acquired in 20 healthy controls (HCs) and 20 multiple sclerosis (MS) patients. All scans were segmented using Heidelberg software and a Johns Hopkins University (JHU)-developed method. Agreement was analyzed using Bland-Altman analyses and intra-class correlation coefficients (ICCs). Using both segmentation techniques, mean differences (agreement at the cohort level) in the thicknesses of all macular layers derived from both acquisition protocols in MS patients and HCs were narrow (<1 µm), while the limits of agreement (LOA) (agreement at the individual level) were wider. Using JHU segmentation mean differences (and LOA) for the macular retinal nerve fiber layer (RNFL) and ganglion cell layer + inner plexiform layer (GCIP) in MS were 0.21 µm (-1.57-1.99 µm) and -0.36 µm (-1.44-1.37 µm), respectively. OCT segmentation measures of discrete retinal-layer thicknesses derived from both vertical and horizontal protocols on Spectralis OCT agree excellently at the cohort level (narrow mean differences), but only moderately at the individual level (wide LOA). This suggests patients scanned using either protocol should continue to be scanned with the same protocol. However, due to excellent agreement at the cohort level, measures derived from both acquisitions can be pooled for outcome purposes in clinical trials.

New Normative Database of Inner Macular Layer Thickness Measured by Spectralis OCT Used as Reference Standard for Glaucoma Detection.

PubMed

Nieves-Moreno, María; Martínez-de-la-Casa, José M; Bambo, María P; Morales-Fernández, Laura; Van Keer, Karel; Vandewalle, Evelien; Stalmans, Ingeborg; García-Feijoó, Julián

2018-02-01

This study examines the capacity to detect glaucoma of inner macular layer thickness measured by spectral-domain optical coherence tomography (SD-OCT) using a new normative database as the reference standard. Participants ( N = 148) were recruited from Leuven (Belgium) and Zaragoza (Spain): 74 patients with early/moderate glaucoma and 74 age-matched healthy controls. One eye was randomly selected for a macular scan using the Spectralis SD-OCT. The variables measured with the instrument's segmentation software were: macular nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) volume and thickness along with circumpapillary RNFL thickness (cpRNFL). The new normative database of macular variables was used to define the cutoff of normality as the fifth percentile by age group. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) of each macular measurement and of cpRNFL were used to distinguish between patients and controls. Overall sensitivity and specificity to detect early-moderate glaucoma were 42.2% and 88.9% for mRNFL, 42.4% and 95.6% for GCL, 42.2% and 94.5% for IPL, and 53% and 94.6% for RNFL, respectively. The best macular variable to discriminate between the two groups of subjects was outer temporal GCL thickness as indicated by an AUROC of 0.903. This variable performed similarly to mean cpRNFL thickness (AUROC = 0.845; P = 0.29). Using our normative database as reference, the diagnostic power of inner macular layer thickness proved comparable to that of peripapillary RNFL thickness. Spectralis SD-OCT, cpRNFL thickness, and individual macular inner layer thicknesses show comparable diagnostic capacity for glaucoma and RNFL, GCL, and IPL thickness may be useful as an alternative diagnostic test when the measure of cpRNFL shows artifacts.

Cosmic Ray Mantle Visibility on Kuiper Belt Objects

NASA Technical Reports Server (NTRS)

Cooper, John F.; Hill, Matt E.; Richardson, J. D.; Sturner, S. J.

2006-01-01

Optically red objects constitute the dynamically cold, old component of the Classical Kuiper Belt (40 - 47 AU) with heliocentric orbits of low eccentricity and inclination. The red colors likely arise from primordial mixed ices processed by irradiation to meters in surface depth over the past four billion years, since the time of giant planet migration and Kuiper Belt stirring, at relatively moderate dosages of 60 gigarads provided by galactic cosmic ray protons and heavier ions. The red cosmic ray mantle is uniformly visible on the cold classical objects beneath a minimally thin eroded layer of more neutrally colored material arising from cumulative effects of heliospheric particle irradiation. The radiation fluxes are lowest in the middle heliospheric region containing the Classical Kuiper Belt and increase from there both towards and away from the Sun. Despite increasing irradiation at various times of solar system history from increases in solar and interstellar ion fluxes, the red object region has apparently never reached sufficiently high dosage levels to neutralize in color the red mantle material. Erosion processes, including plasma sputtering and micrometeroid impacts, act continuously to reduce thickness of the upper neutral crust and expose the cosmic ray mantle. A deeper layer at tens of meters and more may consist of relatively unprocessed ices that can erupt to the surface by larger impacts or cryovolcanism and account for brighter surfaces of larger objects such as 2003 UB313. Surface colors among the Kuiper Belt and other icy objects of the outer solar system are then a function, assuming uniform primordial composition, of relative thickness for the three layers and of the resurfacing age dependent on the orbital and impact history of each object.

Large-scale compositional heterogeneity in the Earth's mantle

NASA Astrophysics Data System (ADS)

Ballmer, M.

2017-12-01

Seismic imaging of subducted Farallon and Tethys lithosphere in the lower mantle has been taken as evidence for whole-mantle convection, and efficient mantle mixing. However, cosmochemical constraints point to a lower-mantle composition that has a lower Mg/Si compared to upper-mantle pyrolite. Moreover, geochemical signatures of magmatic rocks indicate the long-term persistence of primordial reservoirs somewhere in the mantle. In this presentation, I establish geodynamic mechanisms for sustaining large-scale (primordial) heterogeneity in the Earth's mantle using numerical models. Mantle flow is controlled by rock density and viscosity. Variations in intrinsic rock density, such as due to heterogeneity in basalt or iron content, can induce layering or partial layering in the mantle. Layering can be sustained in the presence of persistent whole mantle convection due to active "unmixing" of heterogeneity in low-viscosity domains, e.g. in the transition zone or near the core-mantle boundary [1]. On the other hand, lateral variations in intrinsic rock viscosity, such as due to heterogeneity in Mg/Si, can strongly affect the mixing timescales of the mantle. In the extreme case, intrinsically strong rocks may remain unmixed through the age of the Earth, and persist as large-scale domains in the mid-mantle due to focusing of deformation along weak conveyor belts [2]. That large-scale lateral heterogeneity and/or layering can persist in the presence of whole-mantle convection can explain the stagnation of some slabs, as well as the deflection of some plumes, in the mid-mantle. These findings indeed motivate new seismic studies for rigorous testing of model predictions. [1] Ballmer, M. D., N. C. Schmerr, T. Nakagawa, and J. Ritsema (2015), Science Advances, doi:10.1126/sciadv.1500815. [2] Ballmer, M. D., C. Houser, J. W. Hernlund, R. Wentzcovitch, and K. Hirose (2017), Nature Geoscience, doi:10.1038/ngeo2898.

Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus.

PubMed

Sohn, Elliott H; van Dijk, Hille W; Jiao, Chunhua; Kok, Pauline H B; Jeong, Woojin; Demirkaya, Nazli; Garmager, Allison; Wit, Ferdinand; Kucukevcilioglu, Murat; van Velthoven, Mirjam E J; DeVries, J Hans; Mullins, Robert F; Kuehn, Markus H; Schlingemann, Reinier Otto; Sonka, Milan; Verbraak, Frank D; Abràmoff, Michael David

2016-05-10

Diabetic retinopathy (DR) has long been recognized as a microvasculopathy, but retinal diabetic neuropathy (RDN), characterized by inner retinal neurodegeneration, also occurs in people with diabetes mellitus (DM). We report that in 45 people with DM and no to minimal DR there was significant, progressive loss of the nerve fiber layer (NFL) (0.25 μm/y) and the ganglion cell (GC)/inner plexiform layer (0.29 μm/y) on optical coherence tomography analysis (OCT) over a 4-y period, independent of glycated hemoglobin, age, and sex. The NFL was significantly thinner (17.3 μm) in the eyes of six donors with DM than in the eyes of six similarly aged control donors (30.4 μm), although retinal capillary density did not differ in the two groups. We confirmed significant, progressive inner retinal thinning in streptozotocin-induced "type 1" and B6.BKS(D)-Lepr(db)/J "type 2" diabetic mouse models on OCT; immunohistochemistry in type 1 mice showed GC loss but no difference in pericyte density or acellular capillaries. The results suggest that RDN may precede the established clinical and morphometric vascular changes caused by DM and represent a paradigm shift in our understanding of ocular diabetic complications.

The Hippo signaling pathway: a potential therapeutic target is reversed by a Chinese patent drug in rats with diabetic retinopathy.

PubMed

Hao, Gai-Mei; Lv, Tian-Tian; Wu, Yan; Wang, Hong-Liang; Xing, Wei; Wang, Yong; Li, Chun; Zhang, Zi-Jian; Wang, Zheng-Lin; Wang, Wei; Han, Jing

2017-04-04

The Hippo signaling pathway is reported to be involved in angiogenesis, but the roles of the Hippo pathway in diabetic retinopathy have not been addressed. Fufang Xueshuantong Capsule has been used to treat diabetic retinopathy in China; however, the effect of Fufang Xueshuantong Capsule on the Hippo pathway has not been investigated. In this study, diabetes was induced in Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Twenty weeks later, Fufang Xueshuantong Capsule was administered for 12 weeks. When the administration ended, the eyes were isolated for western blot and immunohistochemistry analyses. The levels of P- mammalian sterile 20-like (MST), large tumor suppressor homolog (Lats), P- yes-associated protein (YAP), transcriptional co-activator with PDZ binding motif (TAZ) and TEA domain family members (TEAD) were measured. Diabetic rats had a decreased P-MST level in the inner plexiform layer and reduced expression of P-YAP in the photoreceptor layers of their eyes. In addition, diabetic rats displayed remarkable increases in Lats, TAZ and TEAD in their retinas. Furthermore, Fufang Xueshuantong Capsule restored the changes in the Hippo pathway. The Hippo signaling pathway is important for the progression of diabetic retinopathy and will hopefully be a targeted therapeutic approach for the prevention of diabetic retinopathy.

Retinal oxygen distribution and the role of neuroglobin.

PubMed

Roberts, Paul A; Gaffney, Eamonn A; Luthert, Philip J; Foss, Alexander J E; Byrne, Helen M

2016-07-01

The retina is the tissue layer at the back of the eye that is responsible for light detection. Whilst equipped with a rich supply of oxygen, it has one of the highest oxygen demands of any tissue in the body and, as such, supply and demand are finely balanced. It has been suggested that the protein neuroglobin (Ngb), which is found in high concentrations within the retina, may help to maintain an adequate supply of oxygen via the processes of transport and storage. We construct mathematical models, formulated as systems of reaction-diffusion equations in one-dimension, to test this hypothesis. Numerical simulations show that Ngb may play an important role in oxygen transport, but not in storage. Our models predict that the retina is most susceptible to hypoxia in the regions of the photoreceptor inner segment and inner plexiform layers, where Ngb has the potential to prevent hypoxia and increase oxygen uptake by 30-40 %. Analysis of a simplified model confirms the utility of Ngb in transport and shows that its oxygen affinity ([Formula: see text] value) is near optimal for this process. Lastly, asymptotic analysis enables us to identify conditions under which the piecewise linear and quadratic approximations to the retinal oxygen profile, used in the literature, are valid.

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

An Unusual Association of Microcephalic Osteodysplastic Primordial Dwarfism Type I with Cardiac and Brain Anomalies

PubMed Central

Bhutia, Euden; Verma, Arushi; Gupta, Amit Kumar; Maria, Arti

2014-01-01

Less than 100 cases of primordial dwarfism have been reported worldwide out of which Microcephalic osteodysplastic primordial dwarfism type I comprise about <30 cases. We report a rare case of extreme growth failure in a neonate with primordial dwarfism of antenatal onset due to Microcephalic osteodysplastic primordial dwarfism type I. Our case is also unique in being associated with hitertho unreported association of subpulmonic ventricular septal defect and a dorsal interhemispheric cyst in the brain. PMID:24741545

Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

PubMed Central

Ray, Thomas A; Roy, Suva; Kozlowski, Christopher; Wang, Jingjing; Cafaro, Jon; Hulbert, Samuel W; Wright, Christopher V; Field, Greg D

2018-01-01

A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here, we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism’s importance in forming circuit-specific sublayers. PMID:29611808

Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the mouse olfactory bulb.

PubMed

Garcia, Isabella; Bhullar, Paramjit K; Tepe, Burak; Ortiz-Guzman, Joshua; Huang, Longwen; Herman, Alexander M; Chaboub, Lesley; Deneen, Benjamin; Justice, Nicholas J; Arenkiel, Benjamin R

2016-01-01

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related behaviors. Further, we provide electrophysiological evidence that CRHR1-expressing granule cells functionally respond to CRH ligand, and that the physiological circuitry of CRHR1 knockout mice is abnormal, leading to impaired olfactory behaviors. Together, these data suggest a physiologically relevant role for local CRH signaling towards shaping the neuronal circuitry within the mouse OB.

Genetically engineered mouse models shed new light on the pathogenesis of neurofibromatosis type I-related neoplasms of the peripheral nervous system.

PubMed

Brossier, Nicole M; Carroll, Steven L

2012-05-01

Neurofibromatosis type 1 (NF1), the most common genetic disorder affecting the human nervous system, is characterized by the development of multiple benign Schwann cell tumors in skin and large peripheral nerves. These neoplasms, which are termed dermal and plexiform neurofibromas respectively, have distinct clinical courses; of particular note, plexiform, but not dermal, neurofibromas often undergo malignant progression to form malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy occurring in NF1 patients. In recent years, a number of genetically engineered mouse models have been created to investigate the molecular mechanisms driving the pathogenesis of these tumors. These models have been designed to address key questions including: (1) whether NF1 loss in the Schwann cell lineage is essential for tumorigenesis; (2) what cell type(s) in the Schwann cell lineage gives rise to dermal neurofibromas, plexiform neurofibromas and MPNSTs; (3) how the tumor microenvironment contributes to neoplasia; (4) what additional mutations contribute to neurofibroma-MPNST progression; (5) what role different neurofibromin-regulated Ras proteins play in this process and (6) how dysregulated growth factor signaling facilitates PNS tumorigenesis. In this review, we summarize the major findings from each of these models and their limitations as well as how discrepancies between these models may be reconciled. We also discuss how information gleaned from these models can be synthesized to into a comprehensive model of tumor formation in peripheral nervous system and consider several of the major questions that remain unanswered about this process. Copyright © 2011 Elsevier Inc. All rights reserved.

Massive plexiform neurofibromas in childhood: natural history and management issues.

PubMed

Serletis, Demitre; Parkin, Patricia; Bouffet, Eric; Shroff, Manohar; Drake, James M; Rutka, James T

2007-05-01

The authors review their experience with massive plexiform neurofibromas (PNs) in patients with pediatric neurofibromatosis Type 1 (NF1) to better characterize the natural history and management of these complex lesions. The authors performed a retrospective review of data obtained in seven patients with NF1 in whom massive PNs were diagnosed at The Hospital for Sick Children in Toronto, Ontario, Canada. These patients attended routine follow-up examinations conducted by a number of specialists, and serial neuroimaging studies were obtained to monitor disease progression. The most common presenting feature of PN was that of a painful, expanding lesion. Furthermore, two patients harbored multiple, distinct PNs affecting different body sites. With respect to management, two patients were simply observed, undergoing serial neuroimaging studies; two patients underwent biopsy sampling of their plexiform lesions; two patients underwent attempted medical treatment (farnesyl transferase inhibitor, R11577, and cyclophosphamide chemotherapy); and three patients required surgical debulking of their PNs because the massive growth of these tumors caused functional compromise. Ultimately, one patient died of respiratory complications due to progressive growth of the massive PN lesion. In this review of their experience, the authors found certain features that underscore the presentation and natural history of PNs. The management of these complex lesions, however, remains unclear. Slow-growing PNs may be observed conservatively, but the authors' experience suggests that resection should be considered in selected cases involving significant deterioration or functional compromise. Nevertheless, patients with massive PNs will benefit from close surveillance by a team of specialists to monitor for ongoing disease progression.

Recurrent plexiform schwannoma involving the carotid canal.

PubMed

Ijichi, Kei; Muto, Masahiro; Masaki, Ayako; Murakami, Shingo

2018-04-01

Plexiform schwannoma (PS) is a rare variety of benign nerve sheath tumor characterized by a multinodular plexiform growth pattern. PS is usually confined to the head and neck or skin. The pre-operative diagnosis of PS is difficult, and this has lead to a common misdiagnosis as a schwannoma. In addition, studies have indicated that an incomplete resection of PS often results in tumor recurrence. Here we describe a rare case of PS presented in the parapharyngeal space. Our case involved a 36-year-old man with swelling of the pharynx, who presented with a soft cervical mass. MRI revealed a multinodular mass in the left parapharyngeal space, and further pathological diagnosis by the referral hospital indicated schwannoma. A cervical approach was taken and the tumor was removed with preservation of the nerve sheath by intracapsular resection. The tumor recurred within one year after the first surgery in the same lesion of the left parapharyngeal space. The second surgical approach was a combination of a facial dismasking flap and trans-pterygopalatine fossa. The mass was resected completely, and the diagnosis of PS was confirmed by histopathology. While schwannoma commonly occurs in the head and neck, parapharyngeal space PS is rare, and pre-operative pathological diagnosis of PS is difficult. MRI studies of PS revealed distinctive features that we found useful in pre-operative diagnosis. Intracapsular resection of PS with nerve preservation has a very high recurrence rate of the tumor. Therefore, if MRI findings suggest PS we recommend removing the tumor completely without nerve preservation will offer the most curative outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

Rocks of the early lunar crust

NASA Technical Reports Server (NTRS)

James, O. B.

1980-01-01

Data are summarized which suggest a model for the early evolution of the lunar crust. According to the model, during the final stages of accretion, the outer part of the moon melted to form a magma ocean approximately 300 km deep. This ocean fractionated to form mafic and ultramafic cumulates at depth and an overlying anorthositic crust made up of ferroan anorthosites. Subsequent partial melting in the primitive mantle underlying the crystallized magma ocean produced melts which segregated, moved upward, intruded the primordial crust, and crystallized to form layered plutons consisting of Mg-rich plutonic rocks. Intense impact bombardment at the lunar surface mixed and melted the rocks of the two suites to form a thick layer of granulated debris, granulitic breccias, and impact-melt rocks.

The Internal Structure of Jupiter Family Comet Nuclei: The Talps or Layered Pile Model

NASA Astrophysics Data System (ADS)

Belton, Michael J.; Members of theDeep Impact Science Team

2006-09-01

The characteristics of layered structures seen on the nucleus of Tempel 1 in the Deep Impact images, and also seen on Wild 2 and Borrelly are noted. We consider the implications of the hypothesis that such structures are ubiquitous on Jupiter Family Comets and is an essential element of their internal stucture. If correct this hypothesis implies that the internal structure of JFCs are primordial remnants of the early agglomeration phase and that the physical structure of their interiors, except for possible compositional changes, is essentially as it was when they were formed. This hypothesis has implications for their place of origin and their subsequent collisional evolution. Current models of the latter are in conflict with this hypothesis. Possible resolutions of this conflict are noted. A new conceptual model of the interior of a typical JFC called the Talps or "layered pile" model is presented.

Progesterone regulation of primordial follicle assembly in bovine fetal ovaries.

PubMed

Nilsson, Eric E; Skinner, Michael K

2009-12-10

Fertility in mammals is dependant on females having an adequate primordial follicle pool to supply oocytes for fertilization. The formation of primordial follicles is called ovarian follicular assembly. In rats and mice progesterone and estradiol have been shown to inhibit follicle assembly with assembly occurring after birth when the pups are removed from the high-steroid maternal environment. In contrast, primordial follicle assembly in other species, such as cattle and humans, occurs during fetal development before birth. The objective of the current study is to determine if progesterone levels regulate primordial follicle assembly in fetal bovine ovaries. Ovaries and blood were collected from bovine fetuses. Interestingly, ovarian progesterone and estradiol concentrations were found to decrease with increasing fetal age and correlated to increased primordial follicle assembly. Microarray analysis of fetal ovary RNA suggests that progesterone membrane receptor and estrogen nuclear receptor are expressed. Treatment of fetal bovine ovary cultures with a higher progesterone concentration significantly decreased primordial follicle assembly. Observations indicate that progesterone affects ovarian primordial follicle assembly in cattle, as it does in rats and mice.

Progesterone Regulation of Primordial Follicle Assembly In Bovine Fetal Ovaries

PubMed Central

Nilsson, Eric E.; Skinner, Michael K.

2009-01-01

Fertility in mammals is dependant on females having an adequate primordial follicle pool to supply oocytes for fertilization. The formation of primordial follicles is called ovarian follicular assembly. In rats and mice progesterone and estradiol have been shown to inhibit follicle assembly with assembly occurring after birth when the pups are removed from the high-steroid maternal environment. In contrast, primordial follicle assembly in other species, such as cattle and humans, occurs during fetal development before birth. The objective of the current study is to determine if progesterone levels regulate primordial follicle assembly in fetal bovine ovaries. Ovaries and blood were collected from bovine fetuses. Interestingly, ovarian progesterone and estradiol concentrations were found to decrease with increasing fetal age and correlated to increased primordial follicle assembly. Microarray analysis of fetal ovary RNA suggests that progesterone membrane receptor and estrogen nuclear receptor are expressed. Treatment of fetal bovine ovary cultures with a higher progesterone concentration significantly decreased primordial follicle assembly. Observations indicate that progesterone affects ovarian primordial follicle assembly in cattle, as it does in rats and mice. PMID:19747959

Toward unraveling a secret of the lower mantle: Detecting and characterizing piles using a grain size-dependent, composite rheology

NASA Astrophysics Data System (ADS)

Schierjott, Jana; Rozel, Antoine; Tackley, Paul

2017-04-01

Seismic studies show two antipodal regions of low shear velocity at the core-mantle boundary (CMB), one beneath the Pacific and one beneath Africa. These regions, called Large Low Shear Velocity Provinces (LLSVPs), are thought to be thermally and chemically distinct and thus have a different density and viscosity. Whereas there is some general consensus about the density of the LLSVPs, their viscosity is still debated. So far, in numerical studies the viscosity is treated as either depth- and/or temperature- dependent but the potential grain size-dependence of the viscosity is neglected most of the time. In this study we use a self-consistent convection model which includes a grain size- dependent rheology based on the approach by Rozel et al. (2011). Further, we consider a basal primordial layer and a time-dependent basalt production to dynamically form the present-day chemical heterogeneities, similar to earlier studies, e.g by Nakagawa & Tackley (2014). Our study comprises three main parts: 1) We perform a parameter study which includes different densities and viscosities of the imposed primordial layer. 2) We detect possible piles and compute their average effective viscosity, density, rheology and grain size. 3) We test the influence of grain size evolution on the development and morphology of piles and compare it to non-grain size models. Our preliminary results show that a higher density and/or viscosity of the piles is needed to keep them at the core-mantle boundary (CMB). Relatively to the ambient mantle grain size is high in the piles but due to the temperature at the CMB the viscosity is not remarkably different than the one of ordinary plumes. We observe that grain size is lower if the density of the imposed primordial material is lower than basalt. In that case the average temperature of the pile is also reduced. Interestingly, changing the reference viscosity is responsible for a change in the average viscosity of the pile but not for a different average grain size.

Primordial dwarfism: an update.

PubMed

Alkuraya, Fowzan S

2015-02-01

To review the recent advances in the clinical and molecular characterization of primordial dwarfism, an extreme growth deficiency disorder that has its onset during embryonic development and persists throughout life. The last decade has witnessed an unprecedented acceleration in the discovery of genes mutated in primordial dwarfism, from one gene to more than a dozen genes. These genetic discoveries have confirmed the notion that primordial dwarfism is caused by defects in basic cellular processes, most notably centriolar biology and DNA damage response. Fortunately, the increasing number of reported clinical primordial dwarfism subtypes has been accompanied by more accurate molecular classification. Qualitative defects of centrioles with resulting abnormal mitosis dynamics, reduced proliferation, and increased apoptosis represent the predominant molecular pathogenic mechanism in primordial dwarfism. Impaired DNA damage response is another important mechanism, which we now know is not mutually exclusive to abnormal centrioles. Molecular characterization of primordial dwarfism is helping families by enabling more reproductive choices and may pave the way for the future development of therapeutics.

Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa.

PubMed

Phillips, M Joseph; Otteson, Deborah C; Sherry, David M

2010-06-01

The Pde6b(rd10) (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6b(rd10) (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well-known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5. (c) 2010 Wiley-Liss, Inc.

Progression of Neuronal and Synaptic Remodeling in the rd10 Mouse Model of Retinitis Pigmentosa

PubMed Central

Phillips, M. Joseph; Otteson, Deborah C.; Sherry, David M.

2010-01-01

The Pde6brd10 (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6brd10 (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5. PMID:20394059

Diagnostic Ability of Wide-field Retinal Nerve Fiber Layer Maps Using Swept-Source Optical Coherence Tomography for Detection of Preperimetric and Early Perimetric Glaucoma.

PubMed

Lee, Won June; Na, Kyeong Ik; Kim, Young Kook; Jeoung, Jin Wook; Park, Ki Ho

2017-06-01

To evaluate the diagnostic ability of wide-field retinal nerve fiber layer (RNFL) maps with swept-source optical coherence tomography (SS-OCT) for detection of preperimetric (PPG) and early perimetric glaucoma (EG). One hundred eighty-four eyes, including 67 healthy eyes, 43 eyes with PPG, and 74 eyes with EG, were analyzed. Patients underwent a comprehensive ocular examination including red-free RNFL photography, visual field testing and wide-field SS-OCT scanning (DRI-OCT-1 Atlantis; Topcon, Tokyo, Japan). SS-OCT provides a wide-field RNFL thickness map and a SuperPixel map, which are composed of the RNFL deviation map of the peripapillary area and the deviation map of the composition of the ganglion cell layer with the inner plexiform layer and RNFL (GC-IPL+RNFL) in the macular area. The ability to discriminate PPG and EG from healthy eyes was assessed using sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for all parameters and criteria provided by the wide-field SS-OCT scan. The wide-field RNFL thickness map using SS-OCT showed the highest sensitivity of PPG-diagnostic and EG-diagnostic performance compared with the other SS-OCT criteria based on the internal normative base (93.0 and 97.3%, respectively). Among the SS-OCT continuous parameters, the RFNL thickness of the 7 clock-hour, inferior and inferotemporal macular ganglion cell analyses showed the largest AUC of PPG-diagnostic and EG-diagnostic performance (AUC=0.809 to 0.865). The wide-field RNFL thickness map using SS-OCT performed well in distinguishing eyes with PPG and EG from healthy eyes. In the clinical setting, wide-field RNFL maps of SS-OCT can be useful tools for detection of early-stage glaucoma.

Olfactory Bulb Deep Short-Axon Cells Mediate Widespread Inhibition of Tufted Cell Apical Dendrites

PubMed Central

LaRocca, Greg

2017-01-01

In the main olfactory bulb (MOB), the first station of sensory processing in the olfactory system, GABAergic interneuron signaling shapes principal neuron activity to regulate olfaction. However, a lack of known selective markers for MOB interneurons has strongly impeded cell-type-selective investigation of interneuron function. Here, we identify the first selective marker of glomerular layer-projecting deep short-axon cells (GL-dSACs) and investigate systematically the structure, abundance, intrinsic physiology, feedforward sensory input, neuromodulation, synaptic output, and functional role of GL-dSACs in the mouse MOB circuit. GL-dSACs are located in the internal plexiform layer, where they integrate centrifugal cholinergic input with highly convergent feedforward sensory input. GL-dSAC axons arborize extensively across the glomerular layer to provide highly divergent yet selective output onto interneurons and principal tufted cells. GL-dSACs are thus capable of shifting the balance of principal tufted versus mitral cell activity across large expanses of the MOB in response to diverse sensory and top-down neuromodulatory input. SIGNIFICANCE STATEMENT The identification of cell-type-selective molecular markers has fostered tremendous insight into how distinct interneurons shape sensory processing and behavior. In the main olfactory bulb (MOB), inhibitory circuits regulate the activity of principal cells precisely to drive olfactory-guided behavior. However, selective markers for MOB interneurons remain largely unknown, limiting mechanistic understanding of olfaction. Here, we identify the first selective marker of a novel population of deep short-axon cell interneurons with superficial axonal projections to the sensory input layer of the MOB. Using this marker, together with immunohistochemistry, acute slice electrophysiology, and optogenetic circuit mapping, we reveal that this novel interneuron population integrates centrifugal cholinergic input with broadly tuned feedforward sensory input to modulate principal cell activity selectively. PMID:28003347

Inner retinal thinning after Brilliant Blue G-assisted internal limiting membrane peeling for vitreoretinal interface disorders.

PubMed

Ambiya, Vikas; Goud, Abhilash; Khodani, Mitali; Chhablani, Jay

2017-04-01

The aim of this study was to evaluate ganglion cell layer and nerve fiber layer thickness after Brilliant Blue G (BBG)-assisted internal limiting membrane (ILM) peeling for vitreomacular disorders. Retrospective analysis of spectral domain optical coherence tomography (SD-OCT) of 42 eyes of 42 patients, who underwent pars plana vitrectomy with BBG-assisted ILM peeling, was performed. Inclusion criteria were idiopathic macular hole, idiopathic vitreomacular traction, and idiopathic epiretinal membrane. Key exclusion criteria were vitreoretinal interface abnormalities secondary to any other diseases, follow-up period of less than 3 months, and any other associated retinal pathology. Average, minimum, and sectoral ganglion cell, and inner plexiform layers (GCIPL) and retinal nerve fiber layer (RNFL) parameters were collected. Changes in these parameters from baseline to 3- and 6-month visits after surgery were analyzed. At 3 months after surgery, we found a statistically significant reduction in the average GCIPL thickness (P = 0.031) and also in the superior sectors (P < 0.05) compared to the baseline values. A similar reduction was observed in the minimum RNFL thickness (P = 0.028) as well as in the superior sectoral RNFL thickness (P < 0.05). In 14 eyes with 6 months of follow-up, a similar statistically significant thinning of the GCIPL and RNFL was observed. However, the difference between the 3-month and 6-month values was not statistically significant (P = 0.679). BBG-assisted ILM peeling for vitreomacular interface disorders leads to thinning of the inner retina including GCIPL and RNFL. These structural changes should be correlated with retinal function tests to explore the pros and cons of this surgical step.

Characteristics of intraretinal deposits in acute central serous chorioretinopathy.

PubMed

Plateroti, Andrea M; Witmer, Matthew T; Kiss, Szilárd; D'Amico, Donald J

2014-01-01

To describe the temporal and spatial characteristics of intraretinal deposits in patients with acute central serous chorioretinopathy (CSC) using spectral domain optical coherence tomography (OCT). We retrospectively reviewed the medical records of all patients that presented with acute CSC to Weill Cornell Medical College from January 2012 to May 2013. Acute CSC was defined as a diagnosis of CSC within 4 months of the onset of symptoms. Only one eye per patient was included in the study. Each patient was imaged with spectral domain OCT at the initial office visit. The decision to reimage these patients was made by the treating physician. A total of 25 patients (25 eyes; 17 men and eight nonpregnant women) were included in this review. Seven of 25 patients (28%) demonstrated intraretinal deposits within the outer plexiform layer during the initial OCT, with deposits appearing as early as the same day as the onset of symptoms. A total of 25 of 25 patients (100%) demonstrated intraretinal deposits in the outer nuclear layer upon initial (76%) or follow-up OCT, as early as 2 days after the onset of symptoms. A total of 24 of 25 patients (96%) demonstrated deposits in the external limiting membrane upon a follow-up OCT, as early as 7 days from symptoms appearing. A total of 24 of 25 patients (96%) developed intraretinal deposits in the inner segment/outer segment layer upon follow-up OCT, appearing as early as 14 days after symptom onset. At the time of resolution of subretinal fluid, 20 of 25 patients (80%) demonstrated intraretinal deposits. Intraretinal deposits are present in the outer retinal layers in patients with acute CSC, with the deposits appearing progressively deeper within the retina as the condition evolves. Upon resolution of subretinal fluid, the deposits slowly resolve.

Growth of Primordial Black Holes

NASA Astrophysics Data System (ADS)

Harada, Tomohiro

Primordial black holes have important observational implications through Hawking evaporation and gravitational radiation as well as being a candidate for cold dark matter. Those black holes are assumed to have formed in the early universe typically with the mass scale contained within the Hubble horizon at the formation epoch and subsequently accreted mass surrounding them. Numerical relativity simulation shows that primordial black holes of different masses do not accrete much, which contrasts with a simplistic Newtonian argument. We see that primordial black holes larger than the 'super-horizon' primordial black holes have decreasing energy and worm-hole like struture, suggesting the formation through quamtum processes.

Clusters of primordial black holes and reionization problem

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

Belotsky, K. M., E-mail: k-belotsky@yandex.ru; Kirillov, A. A., E-mail: kirillov-aa@yandex.ru; Rubin, S. G., E-mail: sergeirubin@list.ru

2015-05-15

Clusters of primordial black holes may cause the formation of quasars in the early Universe. In turn, radiation from these quasars may lead to the reionization of the Universe. However, the evaporation of primordial black holes via Hawking’s mechanism may also contribute to the ionization of matter. The possibility of matter ionization via the evaporation of primordial black holes with allowance for existing constraints on their density is discussed. The contribution to ionization from the evaporation of primordial black holes characterized by their preset mass spectrum can roughly be estimated at about 10{sup −3}.

Primordial Dwarfism

MedlinePlus

... Topics Gait & Motion Analysis Genetic Disorders Limb Length Discrepancy Orthopedics Orthotics Primordial Dwarfism Locations & Doctors About Primordial ... Sign-In » Patient-Family Resources Insurance We Accept Pay My Bill Financial Assistance Medical Records Support Services ...

Angiogenesis and Therapeutic Approaches to NF1 Tumors

DTIC Science & Technology

2006-04-01

history, and pathogenesis. Baltimore: Johns Hopkins University Press. Rizvi TA, Huang Y, Sidani A, Atit R, Largaespada DA, Boissy RE, Ratner N. 2002...29 plexiform and 4 MPNSTs) were immunostained for PR. Interestingly, half of the women contributing tumors to this immunohistochemical analysis

Aberrant ATRX protein expression is associated with poor overall survival in NF1-MPNST

PubMed Central

Lu, Hsiang-Chih; Eulo, Vanessa; Apicelli, Anthony J.; Pekmezci, Melike; Tao, Yu; Luo, Jingqin; Hirbe, Angela C.; Dahiya, Sonika

2018-01-01

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive soft tissue sarcomas that can occur sporadically or in the setting of the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. These tumors carry a dismal overall survival. Previous work in our lab had identified ATRX chromatin remodeler (ATRX), previously termed, Alpha Thalassemia/Mental Retardation Syndrome X Linked as a gene mutated in a subset of MPNSTs. Given the great need for novel biomarkers and therapeutic targets for MPNSTs, we sought to determine the expression of ATRX in a larger subset of sporadic and NF1 associated MPNSTs (NF1-MPNSTs). We performed immunohistochemistry (IHC) on 74 MPNSTs (43 NF1-associated and 31 sporadic), 21 plexiform neurofibromas, and 9 atypical neurofibromas. Using this approach, we have demonstrated that 58% (43/74) of MPNSTs have aberrant ATRX expression (<80% nuclear expression) compared to only 7% (2/30) of benign (plexiform and atypical) neurofibromas. Second, we demonstrated that 65% (28/43) of NF1-MPNSTs displayed aberrant ATRX expression as did 48% (15/31) of sporadic MPNSTs. Finally, we show that aberrant ATRX expression was associated with a significantly decreased overall survival for patients with NF1-MPNST (median OS of 17.9 months for aberrant expression and median OS not met (>120 months) for intact expression, p = 0.0276). In summary, we demonstrate that ATRX is aberrantly expressed in the majority of NF1-MPNSTs, but not plexiform or atypical neurofibromas. Additionally, aberrant ATRX expression is associated with decreased overall survival in NF1-MPNST, but not sporadic MPNST and may serve as a prognostic marker for patients with NF1-MPNST. PMID:29796169

Physics of primordial star formation

NASA Astrophysics Data System (ADS)

Yoshida, Naoki

2012-09-01

The study of primordial star formation has a history of nearly sixty years. It is generally thought that primordial stars are one of the key elements in a broad range of topics in astronomy and cosmology, from Galactic chemical evolution to the formation of super-massive blackholes. We review recent progress in the theory of primordial star formation. The standard theory of cosmic structure formation posits that the present-day rich structure of the Universe developed through gravitational amplification of tiny matter density fluctuations left over from the Big Bang. It has become possible to study primordial star formation rigorously within the framework of the standard cosmological model. We first lay out the key physical processes in a primordial gas. Then, we introduce recent developments in computer simulations. Finally, we discuss prospects for future observations of the first generation of stars.

Osteodysplastic primordial dwarfism: report of a further case with manifestations similar to those of types I and III.

PubMed

Haan, E A; Furness, M E; Knowles, S; Morris, L L; Scott, G; Svigos, J M; Vigneswaren, R

1989-06-01

We describe a male infant with microcephalic osteodysplastic primordial dwarfism. The clinical and radiological manifestations most closely resemble those of the patient described by Winter et al. to have manifestations overlapping with both osteodysplastic primordial dwarfism types I and III. The classification of the patient within the spectrum of osteodysplastic primordial dwarfism is discussed and the distinctive neuropathology documented.

Natural History of Plexiform Neurofibromas in NF1. Addendum

DTIC Science & Technology

2008-10-01

neural foraminal widening, greater sciatic notch widening, and spinal cord com- pression were evaluated. Lesion signal intensity charac- teristics were...neural foraminal widening (n=20), greater sciatic foramina widening (n=2), and neural canal involvement (n=18). Target-like appearance was noted in 53

Von recklinghausen neurofibromatosis-pachydermatocele causing lower limb gigantism: a case report.

PubMed

Rekha, Arcot; Gopalan, T R

2006-03-01

Gigantism of the lower limb can occur because of plexiform neurofibromas. This condition is seen with café au lait patches and multiple neurofibromatosis in this case of von Recklinghausen neurofibromatosis. We report our patient and review literature of this uncommon condition.

Plexiform neurofibroma tissue classification

NASA Astrophysics Data System (ADS)

Weizman, L.; Hoch, L.; Ben Sira, L.; Joskowicz, L.; Pratt, L.; Constantini, S.; Ben Bashat, D.

2011-03-01

Plexiform Neurofibroma (PN) is a major complication of NeuroFibromatosis-1 (NF1), a common genetic disease that involving the nervous system. PNs are peripheral nerve sheath tumors extending along the length of the nerve in various parts of the body. Treatment decision is based on tumor volume assessment using MRI, which is currently time consuming and error prone, with limited semi-automatic segmentation support. We present in this paper a new method for the segmentation and tumor mass quantification of PN from STIR MRI scans. The method starts with a user-based delineation of the tumor area in a single slice and automatically detects the PN lesions in the entire image based on the tumor connectivity. Experimental results on seven datasets yield a mean volume overlap difference of 25% as compared to manual segmentation by expert radiologist with a mean computation and interaction time of 12 minutes vs. over an hour for manual annotation. Since the user interaction in the segmentation process is minimal, our method has the potential to successfully become part of the clinical workflow.

Ultrasonic Wave Properties in Bone Axis Direction of Bovine Cortical Bone

NASA Astrophysics Data System (ADS)

Yamamoto, Kazufumi; Yaoi, Yuichiro; Yamato, Yu; Yanagitan, Takahiko; Matsukawa, Mami; Yamazaki, Kaoru

2008-05-01

Quantitative ultrasonography (QUS) is a good method for measuring elastic properties of bone in vivo. Bovine cortical bone has two typical microstructures, plexiform and Haversian. In this study, the relationship between the speed of sound (SOS) and the hydroxyapatite (HAp) crystallite orientation in the axial direction was investigated in two different aged bovine cortical bones. The dependence of attenuation on anatomical position was also investigated. Two ring-permanent hyphen shaped cortical bone samples were obtained from 36- and 24-month-old bovine femurs. SOS was measured with a conventional ultrasonic pulse system. The integrated intensity of the (0002) peak obtained by X-ray diffraction was determine to evaluate the amount of preferred orientation. Regardless of the age of the bovine femurs, a significant correlation between SOS and the preferred orientation of HAp crystallites was observed in parts of the plexiform structure, and the gradient of the relationship showed a similar tendency. Attenuation seemed to depend on bone microstructure.

[Comparation on Haversian system between human and animal bones by imaging analysis].

PubMed

Lu, Hui-Ling; Zheng, Jing; Yao, Ya-Nan; Chen, Sen; Wang, Hui-Pin; Chen, Li-Xian; Guo, Jing-Yuan

2006-04-01

To explore the differences in Haversian system between human and animal bones through imaging analysis and morphology description. Thirty-five slices grinding from human being as well as dog, pig, cow and sheep bones were observed to compare their structure, then were analysed with the researchful microscope. Plexiform bone or oeston band was not found in human bones; There were significant differences in the shape, size, location, density of Haversian system, between human and animal bones. The amount of Haversian lamella and diameter of central canal in human were the biggest; Significant differences in the central canal diameter and total area percentage between human and animal bones were shown by imaging analysis. (1) Plexiform bone and osteon band could be the exclusive index in human bone; (2) There were significant differences in the structure of Haversian system between human and animal bones; (3) The percentage of central canals total area was valuable in species identification through imaging analysis.

Constraints on the Primordial Black Hole Abundance from the First Advanced LIGO Observation Run Using the Stochastic Gravitational-Wave Background

NASA Astrophysics Data System (ADS)

Wang, Sai; Wang, Yi-Fan; Huang, Qing-Guo; Li, Tjonnie G. F.

2018-05-01

Advanced LIGO's discovery of gravitational-wave events is stimulating extensive studies on the origin of binary black holes. Assuming that the gravitational-wave events can be explained by binary primordial black hole mergers, we utilize the upper limits on the stochastic gravitational-wave background given by Advanced LIGO as a new observational window to independently constrain the abundance of primordial black holes in dark matter. We show that Advanced LIGO's first observation run gives the best constraint on the primordial black hole abundance in the mass range 1 M⊙≲MPBH≲100 M⊙, pushing the previous microlensing and dwarf galaxy dynamics constraints tighter by 1 order of magnitude. Moreover, we discuss the possibility to detect the stochastic gravitational-wave background from primordial black holes, in particular from subsolar mass primordial black holes, by Advanced LIGO in the near future.

Constraints on the Primordial Black Hole Abundance from the First Advanced LIGO Observation Run Using the Stochastic Gravitational-Wave Background.

PubMed

Wang, Sai; Wang, Yi-Fan; Huang, Qing-Guo; Li, Tjonnie G F

2018-05-11

Advanced LIGO's discovery of gravitational-wave events is stimulating extensive studies on the origin of binary black holes. Assuming that the gravitational-wave events can be explained by binary primordial black hole mergers, we utilize the upper limits on the stochastic gravitational-wave background given by Advanced LIGO as a new observational window to independently constrain the abundance of primordial black holes in dark matter. We show that Advanced LIGO's first observation run gives the best constraint on the primordial black hole abundance in the mass range 1M_{⊙}≲M_{PBH}≲100M_{⊙}, pushing the previous microlensing and dwarf galaxy dynamics constraints tighter by 1 order of magnitude. Moreover, we discuss the possibility to detect the stochastic gravitational-wave background from primordial black holes, in particular from subsolar mass primordial black holes, by Advanced LIGO in the near future.

Real-time visual target tracking: two implementations of velocity-based smooth pursuit

NASA Astrophysics Data System (ADS)

Etienne-Cummings, Ralph; Longo, Paul; Van der Spiegel, Jan; Mueller, Paul

1995-06-01

Two systems for velocity-based visual target tracking are presented. The first two computational layers of both implementations are composed of VLSI photoreceptors (logarithmic compression) and edge detection (difference-of-Gaussians) arrays that mimic the outer-plexiform layer of mammalian retinas. The subsequent processing layers for measuring the target velocity and to realize smooth pursuit tracking are implemented in software and at the focal plane in the two versions, respectively. One implentation uses a hybrid of a PC and a silicon retina (39 X 38 pixels) operating at 333 frames/second. The software implementation of a real-time optical flow measurement algorithm is used to determine the target velocity, and a closed-loop control system zeroes the relative velocity of the target and retina. The second implementation is a single VLSI chip, which contains a linear array of photoreceptors, edge detectors and motion detectors at the focal plane. The closed-loop control system is also included on chip. This chip realizes all the computational properties of the hybrid system. The effects of background motion, target occlusion, and disappearance are studied as a function of retinal size and spatial distribution of the measured motion vectors (i.e. foveal/peripheral and diverging/converging measurement schemes). The hybrid system, which tested successfully, tracks targets moving as fast as 3 m/s at 1.3 meters from the camera and it can compensate for external arbitrary movements in its mounting platform. The single chip version, whose circuits tested successfully, can handle targets moving at 10 m/s.

KCNQ5/Kv7.5 potassium channel expression and subcellular localization in primate retinal pigment epithelium and neural retina

PubMed Central

Zhang, Xiaoming; Yang, Dongli

2011-01-01

Previous studies identified in retinal pigment epithelial (RPE) cells an M-type K+ current, which in many other cell types is mediated by channels encoded by KCNQ genes. The aim of this study was to assess the expression of KCNQ genes in the monkey RPE and neural retina. Application of the specific KCNQ channel blocker XE991 eliminated the M-type current in freshly isolated monkey RPE cells, indicating that KCNQ subunits contribute to the underlying channels. RT-PCR analysis revealed the expression of KCNQ1, KCNQ4, and KCNQ5 transcripts in the RPE and all five KCNQ transcripts in the neural retina. At the protein level, KCNQ5 was detected in the RPE, whereas both KCNQ4 and KCNQ5 were found in neural retina. In situ hybridization in frozen monkey retinal sections revealed KCNQ5 gene expression in the ganglion cell layer and the inner and outer nuclear layers of the neural retina, but results in the RPE were inconclusive due to the presence of melanin. Immunohistochemistry revealed KCNQ5 in the inner and outer plexiform layers, in cone and rod photoreceptor inner segments, and near the basal membrane of the RPE. The data suggest that KCNQ5 channels contribute to the RPE basal membrane K+ conductance and, thus, likely play an important role in active K+ absorption. The distribution of KCNQ5 in neural retina suggests that these channels may function in the shaping of the photoresponses of cone and rod photoreceptors and the processing of visual information by retinal neurons. PMID:21795522

Investigation of tissue cysts in the retina in a mouse model of ocular toxoplasmosis: distribution and interaction with glial cells.

PubMed

Song, Hyun Beom; Jung, Bong-Kwang; Kim, Jin Hyoung; Lee, Young-Ha; Choi, Min-Ho; Kim, Jeong Hun

2018-06-02

The conversion of tachyzoites into bradyzoites is a way for Toxoplasma gondii to establish a chronic and asymptomatic infection and achieve lifelong persistence in the host. The bradyzoites form tissue cysts in the retina, but not much is known about the horizontal distribution of the cysts or their interactions with glial cells in the retina. A chronic ocular toxoplasmosis model was induced by per oral administration of T. gondii Me49 strain cysts to BALB/c mice. Two months after the infection, retinas were flat-mounted and immunostained to detect cysts, ganglion cells, Müller cells, astrocytes, and microglial cells, followed by observation under fluorescence and confocal microscope. The horizontal distribution showed a rather clustered pattern, but the clusters were not restricted to certain location of the retina. Axial distribution was confined to the inner retina, mostly in ganglion cell layer or the inner plexiform layer. Both ganglion cells, a type of retinal neurons, and Müller cells, predominant retinal glial cells, could harbor cysts. The cysts were spatially separated from astrocytes, the most abundant glial cells in the ganglion cell layer, while close spatial distribution of microglial cells was observed in two thirds of retinal cysts. In this study, we demonstrated that the retinal cysts were not evenly distributed horizontally and were confined to the inner retina axially. Both neurons and one type of glial cells could harbor cysts, and topographic analysis of other glial cells suggests role of microglial cells in chronic ocular toxoplasmosis.

Wide-field Diffuse Amacrine Cells in the Monkey Retina Contain Immunoreactive Cocaine- and Amphetamine-Regulated Transcript (CART)

PubMed Central

Liu, Weiley S.; Davis, Elizabeth P.; Lee, Stephen J.; Tseng, Luke; Chuang, Alice Z.; Whitaker, Christopher M.; Massey, Stephen C.; Sherman, Michael B.; Marshak, David W.

2016-01-01

The goals of this study were to localize the neuropeptide Cocaine- and Amphetamine-Regulated Transcript (CART) in primate retinas and to describe the morphology, neurotransmitter content and synaptic connections of the neurons that contain it. Using in situ hybridization, light and electron microscopic immunolabeling, CART was localized to GABAergic amacrine cells in baboon retinas. The CART-positive cells had thin, varicose dendrites that gradually descended through the inner plexiform layer and ramified extensively in the innermost stratum. They resembled two types of wide-field diffuse amacrine cells that had been described previously in macaque retinas using the Golgi method and also A17, serotonin-accumulating and waterfall cells of other mammals. The CART-positive cells received synapses from rod bipolar cell axons and made synapses onto the axons in a reciprocal configuration. The CART-positive cells also received synapses from other amacrine cells. Some of these were located on their primary dendrites, and the presynaptic cells there included dopaminergic amacrine cells. Although some CART-positive somas were localized in the ganglion cell layer, they did not contain the ganglion cell marker RNA binding protein with multiple splicing (RBPMS). Based on these results and electrophysiological studies in other mammals, the CART-positive amacrine cells would be expected to play a major role in the primary rod pathway of primates, providing feedback inhibition to rod bipolar cells. PMID:27568514

Sensitivity of visual evoked potentials and spectral domain optical coherence tomography in early relapsing remitting multiple sclerosis.

PubMed

Behbehani, Raed; Ahmed, Samar; Al-Hashel, Jasem; Rousseff, Rossen T; Alroughani, Raed

2017-02-01

Visual evoked potentials and spectral-domain optical coherence tomography are common ancillary studies that assess the visual pathways from a functional and structural aspect, respectively. To compare prevalence of abnormalities of Visual evoked potentials (VEP) and spectral-domain optical coherence tomography (SDOCT) in patients with relapsing remitting multiple sclerosis (RRMS). A cross-sectional study of 100 eyes with disease duration of less than 5 years since the diagnosis. Correlation between retinal nerve fiber layer and ganglion-cell/inner plexiform layer with pattern-reversal visual evoked potentials amplitude and latency and contrast sensitivity was performed. The prevalence of abnormalities in pattern-reversal visual VEP was 56% while that of SOCT was 48% in all eyes. There was significant negative correlations between the average RNFL (r=-0.34, p=0.001) and GCIPL (r=-0.39, p<0.001) with VEP latency. In eyes with prior optic neuritis, a significant negative correlation was seen between average RNFL (r=-0.33, p=0.037) and GCIPL (r=-0.40, p=0.010) with VEP latency. We have found higher prevalence of VEP abnormalities than SCOCT in early relapsing-remitting multiple sclerosis. This suggests that VEP has a higher sensitivity for detecting lesions of the visual pathway in patients with early RRMS. Copyright © 2016 Elsevier B.V. All rights reserved.

Organization of the main olfactory bulbs of some mammals: musk shrews, moles, hedgehogs, tree shrews, bats, mice, and rats.

PubMed

Kosaka, Katsuko; Kosaka, Toshio

2004-04-19

We immunohistochemically examined the organization of the main olfactory bulbs (MOBs) in seven mammalian species, including moles, hedgehogs, tree shrews, bats, and mice as well as laboratory musk shrews and rats. We focused our investigation on two points: 1) whether nidi, particular spheroidal synaptic regions subjacent to glomeruli, which we previously reported for the laboratory musk shrew MOBs, are also present in other animals and 2) whether the compartmental organization of glomeruli and two types of periglomerular cells we proposed for the rat MOBs are general in other animals. The general laminar pattern was similar among these seven species, but discrete nidi and the nidal layer were recognized only in two insectivores, namely, the mole and laboratory musk shrew. Olfactory marker protein-immunoreactive (OMP-IR) axons extended beyond the limits of the glomerular layer (GL) into the superficial region of the external plexiform layer (EPL) or the nidal layer in the laboratory musk shrew, mole, hedgehog, and tree shrew but not in bat, mouse, and rat. We observed, in nidi and the nidal layer in the mole and laboratory musk shrew MOBs, only a few OMP-IR axons. In the hedgehog, another insectivore, OMP-IR processes extending from the glomeruli were scattered and intermingled with calbindin D28k-IR cells at the border between the GL and the EPL. In the superficial region of the EPL of the tree shrew MOBs, there were a small number of tiny glomerulus-like spheroidal structures where OMP-IR axons protruding from glomeruli were intermingled with dendritic branches of surrounding calbindin D28k-IR cells. Furthermore, we recognized the compartmental organization of glomeruli and two types of periglomerular cells in the MOBs of all of the mammals we examined. These structural features are therefore considered to be common and important organizational principles of the MOBs. Copyright 2004 Wiley-Liss, Inc.

Asymmetry Analysis of Macular Inner Retinal Layers for Glaucoma Diagnosis: Swept-Source Optical Coherence Tomography Study.

PubMed

Lee, Sang-Yoon; Lee, Eun Kyoung; Park, Ki Ho; Kim, Dong Myung; Jeoung, Jin Wook

2016-01-01

To report an asymmetry analysis of macular inner retinal layers using swept-source optical coherence tomography (OCT) and to evaluate the utility for glaucoma diagnosis. Observational, cross-sectional study. Seventy normal healthy subjects and 62 glaucoma patients. Three-dimensional scans were acquired from 70 normal subjects and 62 open angle glaucoma patients by swept-source OCT. The thickness of the retinal nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex, and total retina were calculated within a 6.2×6.2 mm macular area divided into a 31×31 grid of 200×200 μm superpixels. For each of the corresponding superpixels, the thickness differences between the subject eyes and contra-lateral eyes and between the upper and lower macula halves of the subject eyes were determined. The negative differences were displayed on a gray-scale asymmetry map. Black superpixels were defined as thickness decreases over the cut-off values. The negative inter-ocular and inter-hemisphere differences in GCIPL thickness (mean ± standard deviation) were -2.78 ± 0.97 μm and -3.43 ± 0.71 μm in the normal group and -4.26 ± 2.23 μm and -4.88 ± 1.46 μm in the glaucoma group. The overall extent of the four layers' thickness decrease was larger in the glaucoma group than in the normal group (all Ps<0.05). The numbers of black superpixels on all of the asymmetry maps were larger in the glaucoma group than in the normal group (all Ps<0.05). The area under receiver operating characteristic curves of average negative thickness differences in macular inner layers for glaucoma diagnosis ranged from 0.748 to 0.894. The asymmetry analysis of macular inner retinal layers showed significant differences between the normal and glaucoma groups. The diagnostic performance of the asymmetry analysis was comparable to that of previous methods. These findings suggest that the asymmetry analysis can be a potential ancillary diagnostic tool.

Primordial black holes from fifth forces

NASA Astrophysics Data System (ADS)

Amendola, Luca; Rubio, Javier; Wetterich, Christof

2018-04-01

Primordial black holes can be produced by a long-range attractive fifth force stronger than gravity, mediated by a light scalar field interacting with nonrelativistic "heavy" particles. As soon as the energy fraction of heavy particles reaches a threshold, the fluctuations rapidly become nonlinear. The overdensities collapse into black holes or similar screened objects, without the need for any particular feature in the spectrum of primordial density fluctuations generated during inflation. We discuss whether such primordial black holes can constitute the total dark matter component in the Universe.

Constraints on small-scale primordial power by annihilation signals from extragalactic dark matter minihalos

NASA Astrophysics Data System (ADS)

Nakama, Tomohiro; Suyama, Teruaki; Kohri, Kazunori; Hiroshima, Nagisa

2018-01-01

We revisit constraints on small-scale primordial power from annihilation signals from dark matter minihalos. Using gamma rays and neutrinos from extragalactic minihalos and assuming the delta-function primordial spectrum, we show the dependence of the constraints on annihilation modes, the mass of dark matter, and the annihilation cross section. We report conservative constraints by assuming minihalos are fully destructed when becoming part of halos originating from the standard almost-scale invariant primordial spectrum and optimistic constraints by neglecting destruction.

Modes of mantle convection and the removal of heat from the earth's interior

NASA Technical Reports Server (NTRS)

Spohn, T.; Schubert, G.

1982-01-01

Thermal histories for two-layer and whole-mantle convection models are calculated and presented, based on a parameterization of convective heat transport. The model is composed of two concentric spherical shells surrounding a spherical core. The models were constrained to yield the observed present-day surface heat flow and mantle viscosity, in order to determine parameters. These parameters were varied to determine their effects on the results. Studies show that whole-mantle convection removes three times more primordial heat from the earth interior and six times more from the core than does two-layer convection (in 4.5 billion years). Mantle volumetric heat generation rates for both models are comparable to that of a potassium-depleted chondrite, and thus surface heat-flux balance does not require potassium in the core. Whole and two-layer mantle convection differences are primarily due to lower mantle thermal insulation and the lower heat removal efficiency of the upper mantle as compared with that of the whole mantle.

Neurotrophin NT3 promotes ovarian primordial to primary follicle transition

PubMed Central

Nilsson, Eric; Dole, Gretchen; Skinner, Michael K

2017-01-01

Neurotrophins are growth factors that are known to have a role in promoting cell survival and differentiation. The focus of the current study is to examine the role of neurotrophins in regulating ovarian primordial follicle development. Ovaries from 4-day old rats were placed into organ culture and cultured for 10 days in the absence or presence of neurotrophin-3 (NT3), brain-derived neurotrophic factor (BDNF), or nerve growth factor (NGF). Treatment of ovaries with NT3 resulted in a significant (P<0.01) increase in primordial follicle development (i.e. primordial to primary follicle transition). Treatment with BDNF at high doses of 100–250 ng/ml also significantly (P<0.01) increased primordial follicle development, but NGF had no effect. Immunohistochemical studies determined that NT3 was present in granulosa cells, interstitial tissue, and in the oocytes of primordial and primary follicles. The NT3 receptor NTRK3 was present in oocytes at all stages of development. Analysis of ovaries that contain predominantly primordial follicles demonstrated the transcripts for NT3, NTRK3, NGF, and the BDNF/neurotrophin-4 (NT4) receptor NTRK2 are expressed, while BDNF, NT4, and the NGF receptor NTRK1 are not detectable. Inhibition of the NTRK3 receptor with the tyrphostin AG 879 resulted in oocyte death and a significant (P<0.01) reduction in follicle pool size. Inhibition of the NTRK receptors with K252a slowed primordial to primary follicle transition. A microarray analysis demonstrated that a small number of genes were differentially expressed after NT3 treatment. Observations indicate that the neurotrophin NT3, acting through the NTRK3 receptor in oocytes, promotes the primordial to primary follicle transition. PMID:19584175

"Ocular moyamoya" syndrome in a patient with features of microcephalic osteodysplastic primordial dwarfism type II.

PubMed

Bang, Genie M; Kirmani, Salman; Patton, Alice; Pulido, Jose S; Brodsky, Michael C

2013-02-01

Primordial dwarfism refers to severely impaired growth beginning early in fetal life. There are many genetic causes of primordial dwarfism, including disorders classified as microcephalic osteodysplastic primordial dwarfism. Microcephalic osteodysplastic primordial dwarfism type II is an autosomal-recessive disease characterized by small stature, bone and dental anomalies, and characteristic facies. Affected patients have a high risk of stroke secondary to progressive cerebral vascular anomalies, which often are classified as moyamoya disease. We present the case of a boy with features suggestive of MOPD II with unilateral moyamoya cerebrovascular changes and correlative moyamoya collaterals involving the iris of the ipsilateral eye. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

The Atacama Cosmology Telescope: A Measurement of the Primordial Power Spectrum

NASA Technical Reports Server (NTRS)

Hlozek, Renee; Dunkley, Joanna; Addison, Graeme; Appel, John William; Bond, J. Richard; Carvalho, C. Sofia; Das, Sudeep; Devlin, Mark J.; Duenner, Rolando; Essinger-Hileman, Thomas;

Primordial non-Gaussianity and reionization

NASA Astrophysics Data System (ADS)

Lidz, Adam; Baxter, Eric J.; Adshead, Peter; Dodelson, Scott

2013-07-01

The statistical properties of the primordial perturbations contain clues about their origins. Although the Planck collaboration has recently obtained tight constraints on primordial non-Gaussianity from cosmic microwave background measurements, it is still worthwhile to mine upcoming data sets in an effort to place independent or competitive limits. The ionized bubbles that formed at redshift z˜6-20 during the epoch of reionization were seeded by primordial overdensities, and so the statistics of the ionization field at high redshift are related to the statistics of the primordial field. Here we model the effect of primordial non-Gaussianity on the reionization field. The epoch and duration of reionization are affected, as are the sizes of the ionized bubbles, but these changes are degenerate with variations in the properties of the ionizing sources and the surrounding intergalactic medium. A more promising signature is the power spectrum of the spatial fluctuations in the ionization field, which may be probed by upcoming 21 cm surveys. This has the expected 1/k2 dependence on large scales, characteristic of a biased tracer of the matter field. We project how well upcoming 21 cm observations will be able to disentangle this signal from foreground contamination. Although foreground cleaning inevitably removes the large-scale modes most impacted by primordial non-Gaussianity, we find that primordial non-Gaussianity can be separated from foreground contamination for a narrow range of length scales. In principle, futuristic redshifted 21 cm surveys may allow constraints competitive with Planck.

Luteinizing hormone-releasing hormone (LHRH) in rat olfactory systems.

PubMed

Witkin, J W; Silverman, A J

1983-08-20

The luteinizing hormone-releasing hormone (LHRH) systems of rat olfactory bulbs and nasal areas were studied in neonatal and adult rats. Animals were perfused with Zamboni's fixative and olfactory bulbs with nasal olfactory areas intact were removed, postfixed, and decalcified. LHRH was immunohistochemically demonstrated in unembedded frozen or vibratome sections. Luteinizing hormone-releasing hormone immunoreactive elements were found along the course of the nervus terminalis (NT) and within both the main and accessory olfactory bulbs (MOB and AOB, respectively). Both LHRH neurons and fibers were present in the AOB, but only fibers were detected in the MOB. The fibers of the AOB were not confined to any particular lamina while fibers in the MOB were found mainly in the external plexiform layer. LHRH fibers were found in the mucosa of the olfactory epithelium of the vomeronasal organ in both neonatal and adult rats. The NT probably serves as a source of LHRH fibers for both the AOB and the MOB and for fibers observed in the olfactory epithelium of the vomeronasal organ. Other likely sources of LHRH fibers in the olfactory bulb are discussed.

Microglia in the Retina: Roles in Development, Maturity, and Disease.

PubMed

Silverman, Sean M; Wong, Wai T

2018-05-31

Microglia, the primary resident immune cell type, constitute a key population of glia in the retina. Recent evidence indicates that microglia play significant functional roles in the retina at different life stages. During development, retinal microglia regulate neuronal survival by exerting trophic influences and influencing programmed cell death. During adulthood, ramified microglia in the plexiform layers interact closely with synapses to maintain synaptic structure and function that underlie the retina's electrophysiological response to light. Under pathological conditions, retinal microglia participate in potentiating neurodegeneration in diseases such as glaucoma, retinitis pigmentosa, and age-related neurodegeneration by producing proinflammatory neurotoxic cytokines and removing living neurons via phagocytosis. Modulation of pathogenic microglial activation states and effector mechanisms has been linked to neuroprotection in animal models of retinal diseases. These findings have led to the design of early proof-of-concept clinical trials with microglial modulation as a therapeutic strategy. Expected final online publication date for the Annual Review of Vision Science Volume 4 is September 15, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The goldfish nervus terminalis: a luteinizing hormone-releasing hormone and molluscan cardioexcitatory peptide immunoreactive olfactoretinal pathway.

PubMed

Stell, W K; Walker, S E; Chohan, K S; Ball, A K

1984-02-01

Antisera to two putative neurotransmitters, luteinizing hormone-releasing hormone (LHRH) and molluscan cardioexcitatory tetrapeptide (H-Phe-Met-Arg-Phe-NH2; FMRF-amide), bind specifically to neurites in the inner nuclear and inner plexiform layers of the goldfish retina. Retrograde labeling showed that intraocular axon terminals originate from the nervus terminalis, whose cell bodies are located in the olfactory nerves. Double immunocytochemical and retrograde labeling showed that some terminalis neurons project to the retina; others may project only within the brain. All terminalis neurons having proven retinal projections were both LHRH- and FMRF-amide-immunoreactive. The activity of retinal ganglion cells was recorded with microelectrodes in isolated superfused goldfish retinas. In ON- and OFF-center double-color-opponent cells, micromolar FMRF-amide and salmon brain gonadotropin-releasing factor ( [Trp7, Leu8] LHRH) caused increased spontaneous activity in the dark, loss of light-induced inhibition, and increased incidence of light-entrained pulsatile response. The nervus terminalis is therefore a putatively peptidergic retinopetal projection. Sex-related olfactory stimuli may act through it, thereby modulating the output of ganglion cells responsive to color contrast.

Effect of ovarian aging on androgen biosynthesis in a cynomolgus macaque model

PubMed Central

Ethun, K. F.; Wood, C. E.; Parker, C. R.; Kaplan, J. R.; Chen, H.; Appt, S. E.

2013-01-01

Objective The role of androgens in chronic disease pathogenesis, cognitive function and libido during menopause is of increasing interest. The aim of this study was to characterize the distribution and expression of androgenic proteins in the macaque ovary and to investigate the relationship between serum androgen concentrations, follicle number, and the persistence of androgenesis in the aging macaque ovary. Methods The subjects were 26 adult female cynomolgus macaques. Ovaries were immunostained for cytochrome P450 17α-hydroxylase/17–20 lyase (P450c17), 3β-hydroxysteroid dehydrogenase (3βHSD), and cytochrome b5 (cytb5). Based on primordial follicle counts, animals were divided into tertiles (low (≤200), intermediate (226–1232), and high (2372–4356)) to evaluate differences in androgen staining and changes in serum androgen concentrations following ovariectomy. Results Positive immunostaining for P450c17 and cytb5 within the theca interna layer of growing follicles persisted in advanced atretic follicles and secondary interstitial cells (residual stromal cells). Ovaries with low follicle numbers had less staining for all androgenic proteins compared to ovaries with higher numbers of growing follicles. Immunostaining for cytb5 was the most reliable marker for persistent androgenesis in ovaries with minimal primordial follicle numbers (<100) and residual stromal cells. Following ovariectomy, a significant decrease in testosterone (−27.7%, −30.8%, −27.5%; p < 0.01) and androstenedione (−33.4%, −35.7%, −46.0%; p < 0.01) was observed in monkeys with low, intermediate, and high primordial follicle counts, respectively. Conclusions Despite low follicle numbers, the aging macaque ovary retains the necessary proteins for androgenesis within residual stromal cells and contributes to peripheral androgen concentrations. PMID:21864136

Zebrafish Staufen1 and Staufen2 are required for the survival and migration of primordial germ cells.

PubMed

Ramasamy, Srinivas; Wang, Hui; Quach, Helen Ngoc Bao; Sampath, Karuna

2006-04-15

In sexually reproducing organisms, primordial germ cells (PGCs) give rise to the cells of the germ line, the gametes. In many animals, PGCs are set apart from somatic cells early during embryogenesis. Work in Drosophila, C. elegans, Xenopus, and zebrafish has shown that maternally provided localized cytoplasmic determinants specify the germ line in these organisms (Raz, E., 2003. Primordial germ-cell development: the zebrafish perspective. Nat. Rev., Genet. 4, 690--700; Santos, A.C., Lehmann, R., 2004. Germ cell specification and migration in Drosophila and beyond. Curr. Biol. 14, R578-R589). The Drosophila RNA-binding protein, Staufen is required for germ cell formation, and mutations in stau result in a maternal effect grandchild-less phenotype (Schupbach,T., Weischaus, E., 1989. Female sterile mutations on the second chromosome of Drosophila melanogaster:1. Maternal effect mutations. Genetics 121, 101-17). Here we describe the functions of two zebrafish Staufen-related proteins, Stau1 and Stau2. When Stau1 or Stau2 functions are compromised in embryos by injecting antisense morpholino modified oligonucleotides or dominant-negative Stau peptides, germ layer patterning is not affected. However, expression of the PGC marker vasa is not maintained. Furthermore, expression of a green fluorescent protein (GFP):nanos 3'UTR fusion protein in germ cells shows that PGC migration is aberrant, and the mis-migrating PGCs do not survive in Stau-compromised embryos. Stau2 is also required for survival of neurons in the central nervous system (CNS). These phenotypes are rescued by co-injection of Drosophila stau mRNA. Thus, staufen has an evolutionarily conserved function in germ cells. In addition, we have identified a function for Stau proteins in PGC migration.

Microglia in mouse retina contralateral to experimental glaucoma exhibit multiple signs of activation in all retinal layers

PubMed Central

2014-01-01

Background Glaucomatous optic neuropathy, a leading cause of blindness, can progress despite control of intraocular pressure - currently the main risk factor and target for treatment. Glaucoma progression shares mechanisms with neurodegenerative disease, including microglia activation. In the present model of ocular hypertension (OHT), we have recently described morphological signs of retinal microglia activation and MHC-II upregulation in both the untreated contralateral eyes and OHT eyes. By using immunostaining, we sought to analyze and quantify additional signs of microglia activation and differences depending on the retinal layer. Methods Two groups of adult Swiss mice were used: age-matched control (naïve, n = 12), and lasered (n = 12). In the lasered animals, both OHT eyes and contralateral eyes were analyzed. Retinal whole-mounts were immunostained with antibodies against Iba-1, MHC-II, CD68, CD86, and Ym1. The Iba-1+ cell number in the plexiform layers (PL) and the photoreceptor outer segment (OS), Iba-1+ arbor area in the PL, and area of the retina occupied by Iba-1+ cells in the nerve fiber layer-ganglion cell layer (NFL-GCL) were quantified. Results The main findings in contralateral eyes and OHT eyes were: i) ameboid microglia in the NFL-GCL and OS; ii) the retraction of processes in all retinal layers; iii) a higher level of branching in PL and in the OS; iv) soma displacement to the nearest cell layers in the PL and OS; v) the reorientation of processes in the OS; vi) MHC-II upregulation in all retinal layers; vii) increased CD68 immunostaining; and viii) CD86 immunolabeling in ameboid cells. In comparison with the control group, a significant increase in the microglial number in the PL, OS, and in the area occupied by Iba-1+ cells in the NFL-GCL, and significant reduction of the arbor area in the PL. In addition, rounded Iba-1+ CD86+ cells in the NFL-GCL, OS and Ym1+ cells, and rod-like microglia in the NFL-GCL were restricted to OHT eyes. Conclusions Several quantitative and qualitative signs of microglia activation are detected both in the contralateral and OHT eyes. Such activation extended beyond the GCL, involving all retinal layers. Differences between the two eyes could help to elucidate glaucoma pathophysiology. PMID:25064005

The role of SO2 on Mars and on the primordial oxygen isotope composition of water on Earth and Mars

NASA Technical Reports Server (NTRS)

Waenke, H.; Dreibus, G.; Jagoutz, E.; Mukhin, L. M.

1992-01-01

We stress the importance of SO2 on Mars. In the case that water should have been supplied in sufficient quantities to the Martian surface by a late veneer and stored in the near surface layers in form of ice, temporary greenhouse warming by SO2 after large SO2 discharges may have been responsible for melting of ice and break-out of water in areas not directly connected to volcanic activity. Aside from water, liquid SO2 could explain at least some of the erosion features on the Martian surface.

Membrane guanylate cyclase, a multimodal transduction machine: history, present, and future directions

PubMed Central

Sharma, Rameshwar K.; Duda, Teresa

2014-01-01

A sequel to these authors' earlier comprehensive reviews which covered the field of mammalian membrane guanylate cyclase (MGC) from its origin to the year 2010, this article contains 13 sections. The first is historical and covers MGC from the year 1963–1987, summarizing its colorful developmental stages from its passionate pursuit to its consolidation. The second deals with the establishment of its biochemical identity. MGC becomes the transducer of a hormonal signal and founder of the peptide hormone receptor family, and creates the notion that hormone signal transduction is its sole physiological function. The third defines its expansion. The discovery of ROS-GC subfamily is made and it links ROS-GC with the physiology of phototransduction. Sections ROS-GC, a Ca2+-Modulated Two Component Transduction System to Migration Patterns and Translations of the GCAP Signals Into Production of Cyclic GMP are Different cover its biochemistry and physiology. The noteworthy events are that augmented by GCAPs, ROS-GC proves to be a transducer of the free Ca2+ signals generated within neurons; ROS-GC becomes a two-component transduction system and establishes itself as a source of cyclic GMP, the second messenger of phototransduction. Section ROS-GC1 Gene Linked Retinal Dystrophies demonstrates how this knowledge begins to be translated into the diagnosis and providing the molecular definition of retinal dystrophies. Section Controlled By Low and High Levels of [Ca2+]i, ROS-GC1 is a Bimodal Transduction Switch discusses a striking property of ROS-GC where it becomes a “[Ca2+]i bimodal switch” and transcends its signaling role in other neural processes. In this course, discovery of the first CD-GCAP (Ca2+-dependent guanylate cyclase activator), the S100B protein, is made. It extends the role of the ROS-GC transduction system beyond the phototransduction to the signaling processes in the synapse region between photoreceptor and cone ON-bipolar cells; in section Ca2+-Modulated Neurocalcin δ ROS-GC1 Transduction System Exists in the Inner Plexiform Layer (IPL) of the Retinal Neurons, discovery of another CD-GCAP, NCδ, is made and its linkage with signaling of the inner plexiform layer neurons is established. Section ROS-GC Linkage With Other Than Vision-Linked Neurons discusses linkage of the ROS-GC transduction system with other sensory transduction processes: Pineal gland, Olfaction and Gustation. In the next, section Evolution of a General Ca2+-Interlocked ROS-GC Signal Transduction Concept in Sensory and Sensory-Linked Neurons, a theoretical concept is proposed where “Ca2+-interlocked ROS-GC signal transduction” machinery becomes a common signaling component of the sensory and sensory-linked neurons. Closure to the review is brought by the conclusion and future directions. PMID:25071437

The Risk and Clinical and Molecular Characteristics of Breast Cancer in Women with Neurofibromatosis Type 1

DTIC Science & Technology

2013-10-01

of NF1: Pigmentary changes on skin and eyes (café au lait spots and Lisch nodules), bony dysplasia, scoliosis , short stature, macrocephaly, learning...17 7 Lisch nodules 106 44 Plexiform neurofibroma (PN) 57 23.5 Learning disability (LD) 86 35.5 Vasculopathy 97 40 Scoliosis 72

Running of featureful primordial power spectra

NASA Astrophysics Data System (ADS)

Gariazzo, Stefano; Mena, Olga; Miralles, Victor; Ramírez, Héctor; Boubekeur, Lotfi

2017-06-01

Current measurements of the temperature and polarization anisotropy power spectra of the cosmic microwave background (CMB) seem to indicate that the naive expectation for the slow-roll hierarchy within the most simple inflationary paradigm may not be respected in nature. We show that a primordial power spectrum with localized features could in principle give rise to the observed slow-roll anarchy when fitted to a featureless power spectrum. From a model comparison perspective, and assuming that nature has chosen a featureless primordial power spectrum, we find that, while with mock Planck data there is only weak evidence against a model with localized features, upcoming CMB missions may provide compelling evidence against such a nonstandard primordial power spectrum. This evidence could be reinforced if a featureless primordial power spectrum is independently confirmed from bispectrum and/or galaxy clustering measurements.

Asymmetry Analysis of Macular Inner Retinal Layers for Glaucoma Diagnosis: Swept-Source Optical Coherence Tomography Study

PubMed Central

Lee, Sang-Yoon; Lee, Eun Kyoung; Park, Ki Ho; Kim, Dong Myung

2016-01-01

Purpose To report an asymmetry analysis of macular inner retinal layers using swept-source optical coherence tomography (OCT) and to evaluate the utility for glaucoma diagnosis. Design Observational, cross-sectional study. Participants Seventy normal healthy subjects and 62 glaucoma patients. Methods Three-dimensional scans were acquired from 70 normal subjects and 62 open angle glaucoma patients by swept-source OCT. The thickness of the retinal nerve fiber layer, ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex, and total retina were calculated within a 6.2×6.2 mm macular area divided into a 31×31 grid of 200×200 μm superpixels. For each of the corresponding superpixels, the thickness differences between the subject eyes and contra-lateral eyes and between the upper and lower macula halves of the subject eyes were determined. The negative differences were displayed on a gray-scale asymmetry map. Black superpixels were defined as thickness decreases over the cut-off values. Results The negative inter-ocular and inter-hemisphere differences in GCIPL thickness (mean ± standard deviation) were -2.78 ± 0.97 μm and -3.43 ± 0.71 μm in the normal group and -4.26 ± 2.23 μm and -4.88 ± 1.46 μm in the glaucoma group. The overall extent of the four layers’ thickness decrease was larger in the glaucoma group than in the normal group (all Ps<0.05). The numbers of black superpixels on all of the asymmetry maps were larger in the glaucoma group than in the normal group (all Ps<0.05). The area under receiver operating characteristic curves of average negative thickness differences in macular inner layers for glaucoma diagnosis ranged from 0.748 to 0.894. Conclusions The asymmetry analysis of macular inner retinal layers showed significant differences between the normal and glaucoma groups. The diagnostic performance of the asymmetry analysis was comparable to that of previous methods. These findings suggest that the asymmetry analysis can be a potential ancillary diagnostic tool. PMID:27764166

Primordial blackholes and gravitational waves for an inflection-point model of inflation

NASA Astrophysics Data System (ADS)

Choudhury, Sayantan; Mazumdar, Anupam

2014-06-01

In this article we provide a new closed relationship between cosmic abundance of primordial gravitational waves and primordial blackholes that originated from initial inflationary perturbations for inflection-point models of inflation where inflation occurs below the Planck scale. The current Planck constraint on tensor-to-scalar ratio, running of the spectral tilt, and from the abundance of dark matter content in the universe, we can deduce a strict bound on the current abundance of primordial blackholes to be within a range, 9.99712 ×10-3 <ΩPBHh2 < 9.99736 ×10-3.

Grand unification scale primordial black holes: consequences and constraints.

PubMed

Anantua, Richard; Easther, Richard; Giblin, John T

2009-09-11

A population of very light primordial black holes which evaporate before nucleosynthesis begins is unconstrained unless the decaying black holes leave stable relics. We show that gravitons Hawking radiated from these black holes would source a substantial stochastic background of high frequency gravititational waves (10(12) Hz or more) in the present Universe. These black holes may lead to a transient period of matter-dominated expansion. In this case the primordial Universe could be temporarily dominated by large clusters of "Hawking stars" and the resulting gravitational wave spectrum is independent of the initial number density of primordial black holes.

The origin, evolution and signatures of primordial magnetic fields.

PubMed

Subramanian, Kandaswamy

2016-07-01

The universe is magnetized on all scales probed so far. On the largest scales, galaxies and galaxy clusters host magnetic fields at the micro Gauss level coherent on scales up to ten kpc. Recent observational evidence suggests that even the intergalactic medium in voids could host a weak  ∼  10(-16) Gauss magnetic field, coherent on Mpc scales. An intriguing possibility is that these observed magnetic fields are a relic from the early universe, albeit one which has been subsequently amplified and maintained by a dynamo in collapsed objects. We review here the origin, evolution and signatures of primordial magnetic fields. After a brief summary of magnetohydrodynamics in the expanding universe, we turn to magnetic field generation during inflation and phase transitions. We trace the linear and nonlinear evolution of the generated primordial fields through the radiation era, including viscous effects. Sensitive observational signatures of primordial magnetic fields on the cosmic microwave background, including current constraints from Planck, are discussed. After recombination, primordial magnetic fields could strongly influence structure formation, especially on dwarf galaxy scales. The resulting signatures on reionization, the redshifted 21 cm line, weak lensing and the Lyman-α forest are outlined. Constraints from radio and γ-ray astronomy are summarized. Astrophysical batteries and the role of dynamos in reshaping the primordial field are briefly considered. The review ends with some final thoughts on primordial magnetic fields.

Early changes in retinal structure and BMP2 expression in the retina and crystalline lens of streptozotocin-induced diabetic pigs.

PubMed

Jeong, Jae Seung; Lee, Woon-Kyu; Moon, Yeon Sung; Kim, Na Rae

2017-09-01

This study aims to evaluate early changes in retinal structure and BMP2 expression in the retina and crystalline lens by comparing streptozotocin-induced diabetic pigs and normal control group pigs. Five eye samples from five diabetic Micro-pigs (Medikinetics, Pyeongtaek, Korea) and five eye samples from five control pigs bred in a specific pathogen-free area were used. Diabetes was developed through intravenous injection of nicotinamide and streptozotocin, and the average fasting glucose level was maintained at 250 mg/dL or higher for 16 weeks. To evaluate BMP2 expression in the retina and crystalline lens, Western blotting was performed. In Hematoxylin and Eosin staining, most diabetic pigs showed structural abnormalities in the inner plexiform layer. The number of nuclei in the ganglion cell layer within the range of 10 4 µm 2 was 3.78±0.60 for diabetic pigs and 5.57±1.07 for control group pigs, showing a statistically significant difference. In immunohistochemical staining, diabetic retinas showed an overall increase in BMP2 expression. In Western blotting, the average BMP2/actin level of diabetic retinas was 1.19±0.05, showing a significant increase compared to the 1.06±0.03 of the control group retinas ( P =0.016). The BMP2/actin level of diabetic crystalline lenses was similar to the control group crystalline lenses ( P =0.730). Compared to control group pigs, the number of nuclei in the inner nuclear layer of retinas from streptozotocin-induced diabetic pigs decreased, while an increase in BMP2 expression was observed in the retina of diabetic pigs.

Microperimetric assessment of the two optical coherence tomography subtypes of acute macular neuroretinopathy.

PubMed

Battaglia Parodi, Maurizio; Iacono, Pierluigi; Panico, Daniele; Cascavilla, Marialucia; Bandello, Francesco

2015-01-01

This study evaluates the morpho-functional alterations associated with acute macular neuroretinopathy (AMNR). Prospective observational case series study carried out at the University Vita-Salute, Scientific Institute San Raffaele. Five out of six eyes (three patients) showed the typical features of AMNR. The patients underwent an ophthalmological examination, including best-corrected visual acuity (BCVA) measurement, electroretinogram and electroculogram (ERG/EOG), multifocal electroretinogram (mfERG), infrared reflectance, short wavelength and near-infrared-fundus autofluorescence (SW-FAF/NIR-FAF), spectral-domain optical coherence tomography (SD-OCT) and microperimetry. Microperimetric alterations in the two SD-OCT subtypes of AMNR. The BCVA was 20/20 in all patients. ERG and EOG were normal; mfERG revealed a generally reduced response with a more reduced signal in the areas corresponding to the macular lesions. SD-OCT demonstrated two different patterns of retinal alterations. In case 1, SD-OCT revealed a hyperreflective, plaque-like band at the junction of the outer plexiform layer (OPL) and the inner nuclear layer (INL), extending into the INL (type 1 lesion). In cases 2 and 3, SD-OCT disclosed a hyperreflectivity of the OPL associated with outer nuclear layer thinning and disruption of the outer segment/retinal pigment epithelium junction (type 2 lesion). Microperimetry revealed a wide scotoma involving the entire macular area in all eyes, including the unaffected eye of case 1. The reduction in retinal sensitivity was greatest in type 1. SD-OCT confirms that AMNR may occur in different patterns. Microperimetry demonstrated that functional alterations are also discernible in apparently uninvolved areas. Both examinations are extremely valuable in characterizing the changes associated with AMNR. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

Melanopsin expressing human retinal ganglion cells: Subtypes, distribution, and intraretinal connectivity.

PubMed

Hannibal, Jens; Christiansen, Anders Tolstrup; Heegaard, Steffen; Fahrenkrug, Jan; Kiilgaard, Jens Folke

2017-06-01

Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin belong to a heterogenic population of RGCs which regulate the circadian clock, masking behavior, melatonin suppression, the pupillary light reflex, and sleep/wake cycles. The different functions seem to be associated to different subtypes of melanopsin cells. In rodents, subtype classification has associated subtypes to function. In primate and human retina such classification has so far, not been applied. In the present study using antibodies against N- and C-terminal parts of human melanopsin, confocal microscopy and 3D reconstruction of melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human melanopsin-ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin-ir RGCs, which were named "gigantic M1 (GM1)" and "gigantic displaced M1 (GDM1)." Few M3 cells and no M5 subtypes were labeled. Total cell counts from one male and one female retina revealed that the human retina contains 7283 ± 237 melanopsin-ir (0.63-0.75% of the total number of RGCs). The melanopsin subtypes were unevenly distributed. Most significant was the highest density of M4 cells in the nasal retina. We identified input to the melanopsin-ir RGCs from AII amacrine cells and directly from rod bipolar cells via ribbon synapses in the innermost ON layer of the inner plexiform layer (IPL) and from dopaminergic amacrine cells and GABAergic processes in the outermost OFF layer of the IPL. The study characterizes a heterogenic population of human melanopsin-ir RGCs, which most likely are involved in different functions. © 2017 Wiley Periodicals, Inc.

A Cre Mouse Line for Probing Irradiance- and Direction-Encoding Retinal Networks

PubMed Central

Sabbah, Shai

2017-01-01

Abstract Cell type-specific Cre driver lines have revolutionized the analysis of retinal cell types and circuits. We show that the transgenic mouse Rbp4-Cre selectively labels several retinal neuronal types relevant to the encoding of absolute light intensity (irradiance) and visual motion. In the ganglion cell layer (GCL), most marked cells are wide-field spiking polyaxonal amacrine cells (ACs) with sustained irradiance-encoding ON responses that persist during chemical synaptic blockade. Their arbors spread about 1 mm across the retina and are restricted to the inner half of the ON sublamina of the inner plexiform layer (IPL). There, they costratify with dendrites of M2 intrinsically photosensitive retinal ganglion cells (ipRGCs), to which they are tracer coupled. We propose that synaptically driven and intrinsic photocurrents of M2 cells pass through gap junctions to drive AC light responses. Also marked in this mouse are two types of RGCs. R-cells have a bistratified dendritic arbor, weak directional tuning, and irradiance-encoding ON responses. However, they also receive excitatory OFF input, revealed during ON-channel blockade. Serial blockface electron microscopic (SBEM) reconstruction confirms OFF bipolar input, and reveals that some OFF input derives from a novel type of OFF bipolar cell (BC). R-cells innervate specific layers of the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC). The other marked RGC type (RDS) is bistratified, transient, and ON-OFF direction selective (DS). It apparently innervates the nucleus of the optic tract (NOT). The Rbp4-Cre mouse will be valuable for targeting these cell types for further study and for selectively manipulating them for circuit analysis. PMID:28466070

Expression of sigma receptor 1 mRNA and protein in rat retina.

PubMed

Liu, L L; Wang, L; Zhong, Y M; Yang, X L

2010-06-02

Sigma receptor (sigmaR), known as a unique nonopiate, nonphencyclidine brain receptor, can bind diverse classes of psychotropic drugs, neurosteroids and other synthetic compounds, such as (+)pentazocine, etc. Two types of sigmaRs have been identified: sigmaR1 and sigmaR2. In this work, we examined the expression of sigmaR1 in rat retina by reverse transcription-polymerase chain reactive (RT-PCR) analysis and immunofluorescence double labeling. RT-PCR analysis showed that sigmaR1 mRNA was present in rat retina. Furthermore, labeling for sigmaR1 was diffusely distributed in the outer and inner plexiform layers. The sigmaR1-immunoreactivity (IR) was also observed in many cells in the inner nuclear layer and the ganglion cell layer. In the outer retina sigmaR1 was expressed in all horizontal cells labeled by calbindin. In contrast, no sigmaR1-IR was detected in several subtypes of bipolar cells, including rod-dominant ON-type bipolar cells, types 2, 3, 5 and 8 bipolar cells, labeled by protein kinase C (PKC), recoverin and hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4) respectively. In the inner retina, most of GABAergic amacrine cells, including dopaminergic and cholinergic ones, stained by tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) respectively, expressed sigmaR1. Some glycinergic amacrine cells were also labeled by sigmaR1, but glycinergic AII amacrine cells were not labeled. In addition, sigmaR1-IR was seen in almost all somata of the ganglion cells retrogradely labeled by fluorogold. These results suggest that sigmaR1 may have neuromodulatory and neuroprotective roles in the retina. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Compositional layering within the large low shear-wave velocity provinces in the lower mantle

NASA Astrophysics Data System (ADS)

Ballmer, Maxim D.; Schumacher, Lina; Lekic, Vedran; Thomas, Christine; Ito, Garrett

2016-12-01

The large low shear-wave velocity provinces (LLSVP) are thermochemical anomalies in the deep Earth's mantle, thousands of km wide and ˜1800 km high. This study explores the hypothesis that the LLSVPs are compositionally subdivided into two domains: a primordial bottom domain near the core-mantle boundary and a basaltic shallow domain that extends from 1100 to 2300 km depth. This hypothesis reconciles published observations in that it predicts that the two domains have different physical properties (bulk-sound versus shear-wave speed versus density anomalies), the transition in seismic velocities separating them is abrupt, and both domains remain seismically distinct from the ambient mantle. We here report underside reflections from the top of the LLSVP shallow domain, supporting a compositional origin. By exploring a suite of two-dimensional geodynamic models, we constrain the conditions under which well-separated "double-layered" piles with realistic geometry can persist for billions of years. Results show that long-term separation requires density differences of ˜100 kg/m3 between LLSVP materials, providing a constraint for origin and composition. The models further predict short-lived "secondary" plumelets to rise from LLSVP roofs and to entrain basaltic material that has evolved in the lower mantle. Long-lived, vigorous "primary" plumes instead rise from LLSVP margins and entrain a mix of materials, including small fractions of primordial material. These predictions are consistent with the locations of hot spots relative to LLSVPs, and address the geochemical and geochronological record of (oceanic) hot spot volcanism. The study of large-scale heterogeneity within LLSVPs has important implications for our understanding of the evolution and composition of the mantle.

Somatic cells initiate primordial follicle activation and govern the development of dormant oocytes in mice.

PubMed

Zhang, Hua; Risal, Sanjiv; Gorre, Nagaraju; Busayavalasa, Kiran; Li, Xin; Shen, Yan; Bosbach, Benedikt; Brännström, Mats; Liu, Kui

2014-11-03

The majority of oocytes in the mammalian ovary are dormant oocytes that are enclosed in primordial follicles by several somatic cells, which we refer to as primordial follicle granulosa cells (pfGCs). Very little is known, however, about how the pfGCs control the activation of primordial follicles and the developmental fates of dormant oocytes. By targeting molecules in pfGCs with several mutant mouse models, we demonstrate that the somatic pfGCs initiate the activation of primordial follicles and govern the quiescence or awakening of dormant oocytes. Inhibition of mTORC1 signaling in pfGCs prevents the differentiation of pfGCs into granulosa cells, and this arrests the dormant oocytes in their quiescent states, leading to oocyte death. Overactivation of mTORC1 signaling in pfGCs accelerates the differentiation of pfGCs into granulosa cells and causes premature activation of all dormant oocytes and primordial follicles. We further show that pfGCs trigger the awakening of dormant oocytes through KIT ligand (KITL), and we present an essential communication network between the somatic cells and germ cells that is based on signaling between the mTORC1-KITL cascade in pfGCs and KIT-PI3K signaling in oocytes. Our findings provide a relatively complete picture of how mammalian primordial follicles are activated. The microenvironment surrounding primordial follicles can activate mTORC1-KITL signaling in pfGCs, and these cells trigger the awakening of dormant oocytes and complete the process of follicular activation. Such communication between the microenvironment, somatic cells, and germ cells is essential to maintaining the proper reproductive lifespan in mammals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Noninvasive Imaging of Retinal Morphology and Microvasculature in Obese Mice Using Optical Coherence Tomography and Optical Microangiography

PubMed Central

Zhi, Zhongwei; Chao, Jennifer R.; Wietecha, Tomasz; Hudkins, Kelly L.; Alpers, Charles E.; Wang, Ruikang K.

2014-01-01

Purpose. To evaluate early diabetes-induced changes in retinal thickness and microvasculature in a type 2 diabetic mouse model by using optical coherence tomography (OCT)/optical microangiography (OMAG). Methods. Twenty-two-week-old obese (OB) BTBR mice (n = 10) and wild-type (WT) control mice (n = 10) were imaged. Three-dimensional (3D) data volumes were captured with spectral domain OCT using an ultrahigh-sensitive OMAG scanning protocol for 3D volumetric angiography of the retina and dense A-scan protocol for measurement of the total retinal blood flow (RBF) rate. The thicknesses of the nerve fiber layer (NFL) and that of the NFL to the inner plexiform layer (IPL) were measured and compared between OB and WT mice. The linear capillary densities within intermediate and deep capillary layers were determined by the number of capillaries crossing a 500-μm line. The RBF rate was evaluated using an en face Doppler approach. These quantitative measurements were compared between OB and WT mice. Results. The retinal thickness of the NFL to IPL was significantly reduced in OB mice (P < 0.01) compared to that in WT mice, whereas the NFL thickness between the two was unchanged. 3D depth-resolved OMAG angiography revealed the first in vivo 3D model of mouse retinal microcirculation. Although no obvious differences in capillary vessel densities of the intermediate and deep capillary layers were detected between normal and OB mice, the total RBF rate was significantly lower (P < 0.05) in OB mice than in WT mice. Conclusions. We conclude that OB BTBR mice have significantly reduced NFL–IPL thicknesses and total RBF rates compared with those of WT mice, as imaged by OCT/OMAG. OMAG provides an unprecedented capability for high-resolution depth-resolved imaging of mouse retinal vessels and blood flow that may play a pivotal role in providing a noninvasive method for detecting early microvascular changes in patients with diabetic retinopathy. PMID:24458155

Lrit3 deficient mouse (nob6): a novel model of complete congenital stationary night blindness (cCSNB).

PubMed

Neuillé, Marion; El Shamieh, Said; Orhan, Elise; Michiels, Christelle; Antonio, Aline; Lancelot, Marie-Elise; Condroyer, Christel; Bujakowska, Kinga; Poch, Olivier; Sahel, José-Alain; Audo, Isabelle; Zeitz, Christina

2014-01-01

Mutations in LRIT3, coding for a Leucine-Rich Repeat, immunoglobulin-like and transmembrane domains 3 protein lead to autosomal recessive complete congenital stationary night blindness (cCSNB). The role of the corresponding protein in the ON-bipolar cell signaling cascade remains to be elucidated. Here we genetically and functionally characterize a commercially available Lrit3 knock-out mouse, a model to study the function and the pathogenic mechanism of LRIT3. We confirm that the insertion of a Bgeo/Puro cassette in the knock-out allele introduces a premature stop codon, which presumably codes for a non-functional protein. The mouse line does not harbor other mutations present in common laboratory mouse strains or in other known cCSNB genes. Lrit3 mutant mice exhibit a so-called no b-wave (nob) phenotype with lacking or severely reduced b-wave amplitudes in the scotopic and photopic electroretinogram (ERG), respectively. Optomotor tests reveal strongly decreased optomotor responses in scotopic conditions. No obvious fundus auto-fluorescence or histological retinal structure abnormalities are observed. However, spectral domain optical coherence tomography (SD-OCT) reveals thinned inner nuclear layer and part of the retina containing inner plexiform layer, ganglion cell layer and nerve fiber layer in these mice. To our knowledge, this is the first time that SD-OCT technology is used to characterize an animal model for CSNB. This phenotype is noted at 6 weeks and at 6 months. The stationary nob phenotype of mice lacking Lrit3, which we named nob6, confirms the findings previously reported in patients carrying LRIT3 mutations and is similar to other cCSNB mouse models. This novel mouse model will be useful for investigating the pathogenic mechanism(s) associated with LRIT3 mutations and clarifying the role of LRIT3 in the ON-bipolar cell signaling cascade.

Olfactory Bulb Deep Short-Axon Cells Mediate Widespread Inhibition of Tufted Cell Apical Dendrites.

PubMed

Burton, Shawn D; LaRocca, Greg; Liu, Annie; Cheetham, Claire E J; Urban, Nathaniel N

2017-02-01

In the main olfactory bulb (MOB), the first station of sensory processing in the olfactory system, GABAergic interneuron signaling shapes principal neuron activity to regulate olfaction. However, a lack of known selective markers for MOB interneurons has strongly impeded cell-type-selective investigation of interneuron function. Here, we identify the first selective marker of glomerular layer-projecting deep short-axon cells (GL-dSACs) and investigate systematically the structure, abundance, intrinsic physiology, feedforward sensory input, neuromodulation, synaptic output, and functional role of GL-dSACs in the mouse MOB circuit. GL-dSACs are located in the internal plexiform layer, where they integrate centrifugal cholinergic input with highly convergent feedforward sensory input. GL-dSAC axons arborize extensively across the glomerular layer to provide highly divergent yet selective output onto interneurons and principal tufted cells. GL-dSACs are thus capable of shifting the balance of principal tufted versus mitral cell activity across large expanses of the MOB in response to diverse sensory and top-down neuromodulatory input. The identification of cell-type-selective molecular markers has fostered tremendous insight into how distinct interneurons shape sensory processing and behavior. In the main olfactory bulb (MOB), inhibitory circuits regulate the activity of principal cells precisely to drive olfactory-guided behavior. However, selective markers for MOB interneurons remain largely unknown, limiting mechanistic understanding of olfaction. Here, we identify the first selective marker of a novel population of deep short-axon cell interneurons with superficial axonal projections to the sensory input layer of the MOB. Using this marker, together with immunohistochemistry, acute slice electrophysiology, and optogenetic circuit mapping, we reveal that this novel interneuron population integrates centrifugal cholinergic input with broadly tuned feedforward sensory input to modulate principal cell activity selectively. Copyright © 2017 the authors 0270-6474/17/371117-22$15.00/0.

Y-27632, a Rho-associated protein kinase inhibitor, attenuates neuronal cell death after transient retinal ischemia.

PubMed

Hirata, Akira; Inatani, Masaru; Inomata, Yasuya; Yonemura, Naoko; Kawaji, Takahiro; Honjo, Megumi; Tanihara, Hidenobu

2008-01-01

Transient retinal ischemia induces the death of retinal neuronal cells. Postischemic damage is associated with the infiltration of leukocytes into the neural tissue through vascular endothelia. The current study aimed to investigate whether this damage was attenuated by the inhibition of Rho/ROCK (Rho kinases) signaling, recently shown to play a critical role in the transendothelial migration of leukocytes. Y-27632, a selective inhibitor of ROCK, was injected intravitreally into rat eyes with transient retinal ischemia. Cell loss of the ganglion cell layer (GCL) and thinning of the inner plexiform layer (IPL) with and without the administration of Y-27632 were evaluated by histological analysis, TUNEL assay and retrograde labeling of retinal ganglion cells (RGCs). To examine the attenuation of leukocyte infiltration in postischemic retinas with the administration of Y-27632, silver nitrate staining and immunohistochemistry using an anti-LCA antibody were performed. Cell loss of the GCL and thinning of the IPL were significantly attenuated when 100 nmol Y-27632 was administered within three hours of the induction of ischemia. TUNEL assay and retrograde labeling of RGCs showed a decreased number of apoptotic cells and an increased number of RGCs in Y-27632-injected retinas. Moreover, silver nitrate staining and immunohistochemical analysis using an anti-LCA antibody showed that Y-27632 injection dramatically inhibited leukocyte infiltration and endothelial disarrangement. Our data suggest that inhibition of Rho/ROCK signaling offers neuroprotective therapy against postischemic neural damage, by regulating leukocyte infiltration in the neural tissue.

A putative role for anti-Müllerian hormone (AMH) in optimising ovarian reserve expenditure.

PubMed

Pankhurst, Michael W

2017-04-01

The mammalian ovary has a finite supply of oocytes, which are contained within primordial follicles where they are arrested in a dormant state. The number of primordial follicles in the ovary at puberty is highly variable between females of the same species. Females that enter puberty with a small ovarian reserve are at risk of a shorter reproductive lifespan, as their ovarian reserve is expected to be depleted faster. One of the roles of anti-Müllerian hormone (AMH) is to inhibit primordial follicle activation, which slows the rate at which the ovarian reserve is depleted. A simple interpretation is that the function of AMH is to conserve ovarian reserve. However, the females with the lowest ovarian reserve and the greatest risk of early reserve depletion have the lowest levels of AMH. In contrast, AMH apparently strongly inhibits primordial follicle activation in females with ample ovarian reserve, for reasons that remain unexplained. The rate of primordial follicle activation determines the size of the developing follicle pool, which in turn, determines how many oocytes are available to be selected for ovulation. This review discusses the evidence that AMH regulates the size of the developing follicle pool by altering the rate of primordial follicle activation in a context-dependent manner. The expression patterns of AMH across life are also consistent with changing requirements for primordial follicle activation in the ageing ovary. A potential role of AMH in the fertility of ageing females is proposed herein. © 2017 Society for Endocrinology.

The internal structure of Jupiter family cometary nuclei from Deep Impact observations: The “talps” or “layered pile” model

NASA Astrophysics Data System (ADS)

Belton, Michael J. S.; Thomas, Peter; Veverka, J.; Schultz, Peter; A'Hearn, Michael F.; Feaga, Lori; Farnham, Tony; Groussin, Olivier; Li, Jian-Yang; Lisse, Casey; McFadden, Lucy; Sunshine, Jessica; Meech, Karen J.; Delamere, W. Alan; Kissel, Jochen

2007-03-01

We consider the hypothesis that the layering observed on the surface of Comet 9P/Tempel 1 from the Deep Impact spacecraft and identified on other comet nuclei imaged by spacecraft (i.e., 19P/Borrelly and 81P/Wild 2) is ubiquitous on Jupiter family cometary nuclei and is an essential element of their internal structure. The observational characteristics of the layers on 9P/Tempel 1 are detailed and considered in the context of current theories of the accumulation and dynamical evolution of cometary nuclei. The works of Donn [Donn, B.D., 1990. Astron. Astrophys. 235, 441-446], Sirono and Greenberg [Sirono, S.-I., Greenberg, J.M., 2000. Icarus 145, 230-238] and the experiments of Wurm et al. [Wurm, G., Paraskov, G., Krauss, O., 2005. Icarus 178, 253-263] on the collision physics of porous aggregate bodies are used as basis for a conceptual model of the formation of layers. Our hypothesis is found to have implications for the place of origin of the JFCs and their subsequent dynamical history. Models of fragmentation and rubble pile building in the Kuiper belt in a period of collisional activity (e.g., [Kenyon, S.J., Luu, J.X., 1998. Astron. J. 115, 2136-2160; 1999a. Astron. J. 118, 1101-1119; 1999b. Astrophys. J. 526, 465-470; Farinella, P., Davis, D.R., Stern, S.A., 2000. In: Mannings, V., Boss, A.P., Russell, S.S. (Eds.), Protostars and Planets IV. Univ. of Arizona Press, Tucson, pp. 1255-1282; Durda, D.D., Stern, S.J., 2000. Icarus 145, 220-229]) following the formation of Neptune appear to be in conflict with the observed properties of the layers and irreconcilable with the hypothesis. Long-term residence in the scattered disk [Duncan, M.J., Levison, H.F., 1997. Science 276, 1670-1672; Duncan, M., Levison, H., Dones, L., 2004. In: Festou, M., Keller, H.U., Weaver, H.A. (Eds.), Comets II. Univ. of Arizona Press, Tucson, pp. 193-204] and/or a change in fragmentation outcome modeling may explain the long-term persistence of primordial layers. In any event, the existence of layers places constraints on the environment seen by the population of objects from which the Jupiter family comets originated. If correct, our hypothesis implies that the nuclei of Jupiter family comets are primordial remnants of the early agglomeration phase and that the physical structure of their interiors, except for the possible effects of compositional phase changes, is largely as it was when they were formed. We propose a new model for the interiors of Jupiter family cometary nuclei, called the talps or "layered pile" model, in which the interior consists of a core overlain by a pile of randomly stacked layers. We discuss how several cometary characteristics—layers, surface texture, indications of flow, compositional inhomogeneity, low bulk density low strength, propensity to split, etc., might be explained in terms of this model. Finally, we make some observational predictions and suggest goals for future space observations of these objects.

The internal structure of Jupiter family cometary nuclei from Deep Impact observations: The “talps” or “layered pile” model

NASA Astrophysics Data System (ADS)

Belton, Michael J. S.; Thomas, Peter; Veverka, J.; Schultz, Peter; A'Hearn, Michael F.; Feaga, Lori; Farnham, Tony; Groussin, Olivier; Li, Jian-Yang; Lisse, Casey; McFadden, Lucy; Sunshine, Jessica; Meech, Karen J.; Delamere, W. Alan; Kissel, Jochen

We consider the hypothesis that the layering observed on the surface of Comet 9P/Tempel 1 from the Deep Impact spacecraft and identified on other comet nuclei imaged by spacecraft (i.e., 19P/Borrelly and 81P/Wild 2) is ubiquitous on Jupiter family cometary nuclei and is an essential element of their internal structure. The observational characteristics of the layers on 9P/Tempel 1 are detailed and considered in the context of current theories of the accumulation and dynamical evolution of cometary nuclei. The works of Donn [Donn, B.D., 1990. Astron. Astrophys. 235, 441 446], Sirono and Greenberg [Sirono, S.-I., Greenberg, J.M., 2000. Icarus 145, 230 238] and the experiments of Wurm et al. [Wurm, G., Paraskov, G., Krauss, O., 2005. Icarus 178, 253 263] on the collision physics of porous aggregate bodies are used as basis for a conceptual model of the formation of layers. Our hypothesis is found to have implications for the place of origin of the JFCs and their subsequent dynamical history. Models of fragmentation and rubble pile building in the Kuiper belt in a period of collisional activity (e.g., [Kenyon, S.J., Luu, J.X., 1998. Astron. J. 115, 2136 2160; 1999a. Astron. J. 118, 1101 1119; 1999b. Astrophys. J. 526, 465 470; Farinella, P., Davis, D.R., Stern, S.A., 2000. In: Mannings, V., Boss, A.P., Russell, S.S. (Eds.), Protostars and Planets IV. Univ. of Arizona Press, Tucson, pp. 1255 1282; Durda, D.D., Stern, S.J., 2000. Icarus 145, 220 229]) following the formation of Neptune appear to be in conflict with the observed properties of the layers and irreconcilable with the hypothesis. Long-term residence in the scattered disk [Duncan, M.J., Levison, H.F., 1997. Science 276, 1670 1672; Duncan, M., Levison, H., Dones, L., 2004. In: Festou, M., Keller, H.U., Weaver, H.A. (Eds.), Comets II. Univ. of Arizona Press, Tucson, pp. 193 204] and/or a change in fragmentation outcome modeling may explain the long-term persistence of primordial layers. In any event, the existence of layers places constraints on the environment seen by the population of objects from which the Jupiter family comets originated. If correct, our hypothesis implies that the nuclei of Jupiter family comets are primordial remnants of the early agglomeration phase and that the physical structure of their interiors, except for the possible effects of compositional phase changes, is largely as it was when they were formed. We propose a new model for the interiors of Jupiter family cometary nuclei, called the talps or “layered pile” model, in which the interior consists of a core overlain by a pile of randomly stacked layers. We discuss how several cometary characteristics—layers, surface texture, indications of flow, compositional inhomogeneity, low bulk density low strength, propensity to split, etc., might be explained in terms of this model. Finally, we make some observational predictions and suggest goals for future space observations of these objects.

Nuclear chemistry of returned lunar samples: Nuclide analysis by gamma-ray spectrometry

NASA Technical Reports Server (NTRS)

Okelley, G. D.

1975-01-01

Primordial and cosmogenic radionuclide concentrations are determined nondestructively by gamma-ray spectrometry in soil and rock samples from the returned Apollo 17 sample collection from Taurus-Littrow and Descartes. Geochemical evidence in support of field geology speculation concerning layering of the subfloor basalt flows is demonstrated along with a possible correlation of magmatic fractionation of K/U as a function of depth. The pattern of radionuclide concentrations observed in these samples is distinct due to proton bombardment by the intense solar flares of August 4-9, 1972. Such radionuclide determinations are used in determining lunar sample orientation and characterizing solar flare activity.

Protostar formation in the early universe.

PubMed

Yoshida, Naoki; Omukai, Kazuyuki; Hernquist, Lars

2008-08-01

The nature of the first generation of stars in the universe remains largely unknown. Observations imply the existence of massive primordial stars early in the history of the universe, and the standard theory for the growth of cosmic structure predicts that structures grow hierarchically through gravitational instability. We have developed an ab initio computer simulation of the formation of primordial stars that follows the relevant atomic and molecular processes in a primordial gas in an expanding universe. The results show that primeval density fluctuations left over from the Big Bang can drive the formation of a tiny protostar with a mass 1% that of the Sun. The protostar is a seed for the subsequent formation of a massive primordial star.

Primordial Germ Cell Specification and Migration

PubMed Central

Marlow, Florence

2015-01-01

Primordial germ cells are the progenitor cells that give rise to the gametes. In some animals, the germline is induced by zygotic transcription factors, whereas in others, primordial germ cell specification occurs via inheritance of maternally provided gene products known as germ plasm. Once specified, the primordial germ cells of some animals must acquire motility and migrate to the gonad in order to survive. In all animals examined, perinuclear structures called germ granules form within germ cells. This review focuses on some of the recent studies, conducted by several groups using diverse systems, from invertebrates to vertebrates, which have provided mechanistic insight into the molecular regulation of germ cell specification and migration. PMID:26918157

Neurologic aspects of microcephalic osteodysplastic primordial dwarfism type II.

PubMed

Galasso, Cinzia; Lo-Castro, Adriana; Lalli, Cristina; Cerminara, Caterina; Curatolo, Paolo

2008-06-01

Microcephalic osteodysplastic primordial dwarfism type II is a specific disorder characterized by severe intrauterine and postnatal growth retardation, acquired microcephaly, cerebrovascular abnormalities, progressive bone dysplasia, and a characteristic face. Whereas the diagnostic features of this syndrome are well-recognized, the neurologic aspects have not been clearly defined. We report on a detailed neurodevelopmental follow-up study of a new case of microcephalic osteodysplastic primordial dwarfism type II, followed from the first years of life to adolescence, and we discuss the neurocognitive features of our patient. We also review the neurologic aspects of this disorder compared with syndromes with overlapping phenotypes, such as microcephalic osteodysplastic primordial dwarfism types I and III and Seckel syndrome.

Dark energy from primordial inflationary quantum fluctuations.

PubMed

Ringeval, Christophe; Suyama, Teruaki; Takahashi, Tomo; Yamaguchi, Masahide; Yokoyama, Shuichiro

2010-09-17

We show that current cosmic acceleration can be explained by an almost massless scalar field experiencing quantum fluctuations during primordial inflation. Provided its mass does not exceed the Hubble parameter today, this field has been frozen during the cosmological ages to start dominating the Universe only recently. By using supernovae data, completed with baryonic acoustic oscillations from galaxy surveys and cosmic microwave background anisotropies, we infer the energy scale of primordial inflation to be around a few TeV, which implies a negligible tensor-to-scalar ratio of the primordial fluctuations. Moreover, our model suggests that inflation lasted for an extremely long period. Dark energy could therefore be a natural consequence of cosmic inflation close to the electroweak energy scale.

Scale-dependent CMB power asymmetry from primordial speed of sound and a generalized δ N formalism

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

Wang, Dong-Gang; Cai, Yi-Fu; Zhao, Wen

2016-02-01

We explore a plausible mechanism that the hemispherical power asymmetry in the CMB is produced by the spatial variation of the primordial sound speed parameter. We suggest that in a generalized approach of the δ N formalism the local e-folding number may depend on some other primordial parameters besides the initial values of inflaton. Here the δ N formalism is extended by considering the effects of a spatially varying sound speed parameter caused by a super-Hubble perturbation of a light field. Using this generalized δ N formalism, we systematically calculate the asymmetric primordial spectrum in the model of multi-speed inflation by taking intomore » account the constraints of primordial non-Gaussianities. We further discuss specific model constraints, and the corresponding asymmetry amplitudes are found to be scale-dependent, which can accommodate current observations of the power asymmetry at different length scales.« less

Expanding the phenotypic and mutational spectrum in microcephalic osteodysplastic primordial dwarfism type I.

PubMed

Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Issa, Mahmoud; Magdy, Ahmed; El-Kotoury, Ahmed; Amr, Khalda

2012-06-01

Mutations in the RNU4ATAC gene cause microcephalic osteodysplastic primordial dwarfism type I. It encodes U4atac, a small nuclear RNA that is a component of the minor spliceosome. Six distinct mutations in 30 patients diagnosed as microcephalic osteodysplastic primordial dwarfism type I have been described. We report on three additional patients from two unrelated families presenting with a milder phenotype of microcephalic osteodysplastic primordial dwarfism type I and metopic synostosis. Patient 1 had two novel heterozygous mutations in the 3' prime stem-loop, g.66G > C and g.124G > A while Patients 2 and 3 had a homozygous mutation g.55G > A in the 5' prime stem-loop. Although they manifested the known spectrum of clinical features of microcephalic osteodysplastic primordial dwarfism type I, they lacked evidence of severe developmental delay and neurological symptoms. These findings expand the mutational and phenotypic spectrum of this syndrome. Copyright © 2012 Wiley Periodicals, Inc.

Primordial spectra from sudden turning trajectory

NASA Astrophysics Data System (ADS)

Noumi, Toshifumi; Yamaguchi, Masahide

2013-12-01

Effects of heavy fields on primordial spectra of curvature perturbations are discussed in inflationary models with a sudden turning trajectory. When heavy fields are excited after the sudden turn and oscillate around the bottom of the potential, the following two effects are generically induced: deformation of the inflationary background spacetime and conversion interactions between adiabatic and isocurvature perturbations, both of which can affect the primordial density perturbations. In this paper, we calculate primordial spectra in inflationary models with sudden turning potentials taking into account both of the two effects appropriately. We find that there are some non-trivial correlations between the two effects in the power spectrum and, as a consequence, the primordial scalar power spectrum has a peak around the scale exiting the horizon at the turn. Though both effects can induce parametric resonance amplifications, they are shown to be canceled out for the case with the canonical kinetic terms. The peak feature and the scale dependence of bispectra are also discussed.

Volatile inventory of Mars-2: Primordial sources and fractionating processes

NASA Technical Reports Server (NTRS)

Pepin, R. O.

1987-01-01

The total volatile inventory of Mars has been modeled using meteoritic and presumed primordial abundances in the early solar system. Evidence is presented which indicates that the elemental abundances of the noble gases on Earth and Mars are similar, and their ratios are comparable to those in average carbonaceous chondrites with the exception of xenon and krypton. In order to account for presently observed variations in gas abundances, two primordial sources were used. One was the solar composition similar to the solar wind, and the other of carbonaceous grains that were the source for trace exotic components. For Mars, a model in which the early, high solar EUV flux with continued hydrogen production by differentiation results in mass fractionation of the primordial atmosphere, early depletion of xenon, and later depletion of gases lighter than krypton. The result is that the primordial Mars water inventory may have been on the order of 20 to 30 km if spread over the planet.

Cosmic microwave background trispectrum and primordial magnetic field limits.

PubMed

Trivedi, Pranjal; Seshadri, T R; Subramanian, Kandaswamy

2012-06-08

Primordial magnetic fields will generate non-gaussian signals in the cosmic microwave background (CMB) as magnetic stresses and the temperature anisotropy they induce depend quadratically on the magnetic field. We compute a new measure of magnetic non-gaussianity, the CMB trispectrum, on large angular scales, sourced via the Sachs-Wolfe effect. The trispectra induced by magnetic energy density and by magnetic scalar anisotropic stress are found to have typical magnitudes of approximately a few times 10(-29) and 10(-19), respectively. Observational limits on CMB non-gaussianity from WMAP data allow us to conservatively set upper limits of a nG, and plausibly sub-nG, on the present value of the primordial cosmic magnetic field. This represents the tightest limit so far on the strength of primordial magnetic fields, on Mpc scales, and is better than limits from the CMB bispectrum and all modes in the CMB power spectrum. Thus, the CMB trispectrum is a new and more sensitive probe of primordial magnetic fields on large scales.

Effect of lithium hydride on the cooling of primordial gas

NASA Astrophysics Data System (ADS)

Liu, Boyuan; Bromm, Volker

2018-05-01

We complete the formulation of the standard model of first star formation by exploring the possible impact of LiH cooling, which has been neglected in previous simulations of non-linear collapse. Specifically, we find that at redshift z ≳ 5, the cooling by LiH has no effect on the thermal evolution of shocked primordial gas, and of collapsing primordial gas into minihaloes or relic H II regions, even if the primordial lithium abundance were enhanced by one order of magnitude. Adding the most important lithium species to a minimum network of primordial chemistry, we demonstrate that insufficient LiH is produced in all cases considered, about [LiH/Li] ˜ 10-9 for T ≲ 100 K. Indeed, LiH cooling would only be marginally significant in shocked primordial gas for the highly unlikely case that the LiH abundance were increased by nine orders of magnitude, implying that all lithium would have to be converted into LiH. In this study, photodestruction processes are not considered, and the collisional disassociation rate of LiH is possibly underestimated, rendering our results an extreme upper limit. Therefore, the cooling by LiH can safely be neglected for the thermal evolution of Population III star-forming gas.

Loss of PUMA protects the ovarian reserve during DNA-damaging chemotherapy and preserves fertility.

PubMed

Nguyen, Quynh-Nhu; Zerafa, Nadeen; Liew, Seng H; Morgan, F Hamish; Strasser, Andreas; Scott, Clare L; Findlay, Jock K; Hickey, Martha; Hutt, Karla J

2018-05-23

Female gametes are stored in the ovary in structures called primordial follicles, the supply of which is non-renewable. It is well established that DNA-damaging cancer treatments can deplete the ovarian reserve of primordial follicles, causing premature ovarian failure and infertility. The precise mechanisms underlying this chemotherapy-driven follicle loss are unclear, and this has limited the development of targeted ovarian-protective agents. To address this fundamental knowledge gap, we used gene deletion mouse models to examine the role of the DNA damage-induced pro-apoptotic protein, PUMA, and its transcriptional activator TAp63, in primordial follicle depletion caused by treatment with cyclophosphamide or cisplatin. Cyclophosphamide caused almost complete destruction of the primordial follicle pool in adult wild-type (WT) mice, and a significant destructive effect was also observed for cisplatin. In striking contrast, Puma -/- mice retained 100% of their primordial follicles following either genotoxic treatment. Furthermore, elimination of PUMA alone completely preserved fertility in cyclophosphamide-treated mice, indicating that oocytes rescued from DNA damage-induced death can repair themselves sufficiently to support reproductive function and offspring health. Primordial follicles were also protected in TAp63 -/- mice following cisplatin treatment, but not cyclophosphamide, suggesting mechanistic differences in the induction of apoptosis and depletion of the ovarian reserve in response to these different chemotherapies. These studies identify PUMA as a crucial effector of apoptosis responsible for depletion of primordial follicles following exposure to cyclophosphamide or cisplatin, and this indicates that inhibition of PUMA may be an effective ovarian-protective strategy during cancer treatment in women.

Identification of tissues and patterning events required for distinct steps in early migration of zebrafish primordial germ cells.

PubMed

Weidinger, G; Wolke, U; Köprunner, M; Klinger, M; Raz, E

1999-12-01

In many organisms, the primordial germ cells have to migrate from the position where they are specified towards the developing gonad where they generate gametes. Extensive studies of the migration of primordial germ cells in Drosophila, mouse, chick and Xenopus have identified somatic tissues important for this process and demonstrated a role for specific molecules in directing the cells towards their target. In zebrafish, a unique situation is found in that the primordial germ cells, as marked by expression of vasa mRNA, are specified in random positions relative to the future embryonic axis. Hence, the migrating cells have to navigate towards their destination from various starting positions that differ among individual embryos. Here, we present a detailed description of the migration of the primordial germ cells during the first 24 hours of wild-type zebrafish embryonic development. We define six distinct steps of migration bringing the primordial germ cells from their random positions before gastrulation to form two cell clusters on either side of the midline by the end of the first day of development. To obtain information on the origin of the positional cues provided to the germ cells by somatic tissues during their migration, we analyzed the migration pattern in mutants, including spadetail, swirl, chordino, floating head, cloche, knypek and no isthmus. In mutants with defects in axial structures, paraxial mesoderm or dorsoventral patterning, we find that certain steps of the migration process are specifically affected. We show that the paraxial mesoderm is important for providing proper anteroposterior information to the migrating primordial germ cells and that these cells can respond to changes in the global dorsoventral coordinates. In certain mutants, we observe accumulation of ectopic cells in different regions of the embryo. These ectopic cells can retain both morphological and molecular characteristics of primordial germ cells, suggesting that, in zebrafish at the early stages tested, the vasa-expressing cells are committed to the germ cell lineage.

Primordial power spectrum: a complete analysis with the WMAP nine-year data

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

Hazra, Dhiraj Kumar; Shafieloo, Arman; Souradeep, Tarun, E-mail: dhiraj@apctp.org, E-mail: arman@apctp.org, E-mail: tarun@iucaa.ernet.in

2013-07-01

We have improved further the error sensitive Richardson-Lucy deconvolution algorithm making it applicable directly on the un-binned measured angular power spectrum of Cosmic Microwave Background observations to reconstruct the form of the primordial power spectrum. This improvement makes the application of the method significantly more straight forward by removing some intermediate stages of analysis allowing a reconstruction of the primordial spectrum with higher efficiency and precision and with lower computational expenses. Applying the modified algorithm we fit the WMAP 9 year data using the optimized reconstructed form of the primordial spectrum with more than 300 improvement in χ{sup 2}{sub eff}more » with respect to the best fit power-law. This is clearly beyond the reach of other alternative approaches and reflects the efficiency of the proposed method in the reconstruction process and allow us to look for any possible feature in the primordial spectrum projected in the CMB data. Though the proposed method allow us to look at various possibilities for the form of the primordial spectrum, all having good fit to the data, proper error-analysis is needed to test for consistency of theoretical models since, along with possible physical artefacts, most of the features in the reconstructed spectrum might be arising from fitting noises in the CMB data. Reconstructed error-band for the form of the primordial spectrum using many realizations of the data, all bootstrapped and based on WMAP 9 year data, shows proper consistency of power-law form of the primordial spectrum with the WMAP 9 data at all wave numbers. Including WMAP polarization data in to the analysis have not improved much our results due to its low quality but we expect Planck data will allow us to make a full analysis on CMB observations on both temperature and polarization separately and in combination.« less

Differentiating human bone from animal bone: a review of histological methods.

PubMed

Hillier, Maria L; Bell, Lynne S

2007-03-01

This review brings together a complex and extensive literature to address the question of whether it is possible to distinguish human from nonhuman bone using the histological appearance of cortical bone. The mammalian species included are rat, hare, badger, racoon dog, cat, dog, pig, cow, goat, sheep, deer, horse, water buffalo, bear, nonhuman primates, and human and are therefore not exhaustive, but cover those mammals that may contribute to a North American or Eurasian forensic assemblage. The review has demonstrated that differentiation of human from certain nonhuman species is possible, including small mammals exhibiting Haversian bone tissue and large mammals exhibiting plexiform bone tissue. Pig, cow, goat, sheep, horse, and water buffalo exhibit both plexiform and Haversian bone tissue and where only Haversian bone tissue exists in bone fragments, differentiation of these species from humans is not possible. Other primate Haversian bone tissue is also not distinguishable from humans. Where differentiation using Haversian bone tissue is undertaken, both the general microstructural appearance and measurements of histological structures should be applied. Haversian system diameter and Haversian canal diameter are the most optimal and diagnostic measurements to use. Haversian system density may be usefully applied to provide an upper and lower limit for humans.

Boudinage in nature and experiment

NASA Astrophysics Data System (ADS)

Marques, Fernando O.; Fonseca, Pedro D.; Lechmann, Sarah; Burg, Jean-Pierre; Marques, Ana S.; Andrade, Alexandre J. M.; Alves, Carlos

2012-03-01

Deformation of rocks produces structures at all scales that are in many cases periodic (folding or boudinage), with variable amplitude and wavelength. Here we focus on boudinage, a process of primordial importance for tectonics. In the present study, we carried out measurements of natural boudins and experimentally tested the effects of two variables on boudinage: layer thickness and compression rate. The models were made of a competent layer (mostly brittle, as in nature) of either elastic (soft paper) or viscoelastoplastic (clay) material embedded in a ductile matrix of linear viscous silicone putty. The competent layer lied with its greatest surface normal to the principal shortening axis and greatest length parallel to the principal stretching axis. The model was then subjected to pure shear at constant piston velocity and variable competent layer thickness (Model 1), or at different piston velocity and constant layer thickness (Model 2). The results of Model 1 show an exponential dependence of boudin width on competent layer thickness, in disagreement with data from the studied natural occurrence. This indicates that variables other than competent layer thickness are hidden in the linear relationship obtained for the natural boudinage. The results of Model 2 show that the higher the velocity the smaller the boudin width, following a power-law with exponent very similar to that of analytical predictions. The studied natural boudinage occasionally occurs in two orthogonal directions. This chocolate tablet boudinage can be the result of two successive stages of deformation: buckling followed by stretching of competent sandstone layers, or buckling followed by rotation of reverse limbs into the extensional field of simple shear.

Cosmic microwave background constraints on primordial black hole dark matter

NASA Astrophysics Data System (ADS)

Aloni, Daniel; Blum, Kfir; Flauger, Raphael

2017-05-01

We revisit cosmic microwave background (CMB) constraints on primordial black hole dark matter. Spectral distortion limits from COBE/FIRAS do not impose a relevant constraint. Planck CMB anisotropy power spectra imply that primordial black holes with mBHgtrsim 5 Msolar are disfavored. However, this is susceptible to sizeable uncertainties due to the treatment of the black hole accretion process. These constraints are weaker than those quoted in earlier literature for the same observables.

Ultrasonographic prenatal diagnosis of microcephalic osteodysplastic primordial dwarfism types I/III.

PubMed

Nadjari, M; Fasouliotis, S J; Ariel, I; Raas-Rothschild, A; Bar-Ziv, J; Elchalal, U

2000-08-01

Microcephalic osteodysplastic primordial dwarfism is a rare disease characterized by unique clinical appearance and specific radiographic findings, and distinctive brain abnormalities. We describe the prenatal diagnosis of two siblings with microcephalic osteodysplastic primordial dwarfism types I/III at 23 and 26 weeks of gestation, respectively. Early detection by sequential antenatal sonographic evaluation is important for counselling families known to be at risk of this rare disease. Copyright 2000 John Wiley & Sons, Ltd.

Impairment of photoreceptor ribbon synapses in a novel Pomt1 conditional knockout mouse model of dystroglycanopathy.

PubMed

Rubio-Fernández, Marcos; Uribe, Mary Luz; Vicente-Tejedor, Javier; Germain, Francisco; Susín-Lara, Cristina; Quereda, Cristina; Montoliu, Lluis; de la Villa, Pedro; Martín-Nieto, José; Cruces, Jesús

2018-06-04

Hypoglycosylation of α-dystroglycan (α-DG) resulting from deficiency of protein O-mannosyltransferase 1 (POMT1) may cause severe neuromuscular dystrophies with brain and eye anomalies, named dystroglycanopathies. The retinal involvement of these disorders motivated us to generate a conditional knockout (cKO) mouse experiencing a Pomt1 intragenic deletion (exons 3-4) during the development of photoreceptors, mediated by the Cre recombinase expressed from the cone-rod homeobox (Crx) gene promoter. In this mouse, retinal α-DG was unglycosylated and incapable of binding laminin. Retinal POMT1 deficiency caused significant impairments in both electroretinographic recordings and optokinetic reflex in Pomt1 cKO mice, and immunohistochemical analyses revealed the absence of β-DG and of the α-DG-interacting protein, pikachurin, in the outer plexiform layer (OPL). At the ultrastructural level, noticeable alterations were observed in the ribbon synapses established between photoreceptors and bipolar cells. Therefore, O-mannosylation of α-DG in the retina carried out by POMT1 is crucial for the establishment of proper synapses at the OPL and transmission of visual information from cones and rods to their postsynaptic neurons.

The goldfish nervus terminalis: a luteinizing hormone-releasing hormone and molluscan cardioexcitatory peptide immunoreactive olfactoretinal pathway.

PubMed Central

Stell, W K; Walker, S E; Chohan, K S; Ball, A K

1984-01-01

Antisera to two putative neurotransmitters, luteinizing hormone-releasing hormone (LHRH) and molluscan cardioexcitatory tetrapeptide (H-Phe-Met-Arg-Phe-NH2; FMRF-amide), bind specifically to neurites in the inner nuclear and inner plexiform layers of the goldfish retina. Retrograde labeling showed that intraocular axon terminals originate from the nervus terminalis, whose cell bodies are located in the olfactory nerves. Double immunocytochemical and retrograde labeling showed that some terminalis neurons project to the retina; others may project only within the brain. All terminalis neurons having proven retinal projections were both LHRH- and FMRF-amide-immunoreactive. The activity of retinal ganglion cells was recorded with microelectrodes in isolated superfused goldfish retinas. In ON- and OFF-center double-color-opponent cells, micromolar FMRF-amide and salmon brain gonadotropin-releasing factor ( [Trp7, Leu8] LHRH) caused increased spontaneous activity in the dark, loss of light-induced inhibition, and increased incidence of light-entrained pulsatile response. The nervus terminalis is therefore a putatively peptidergic retinopetal projection. Sex-related olfactory stimuli may act through it, thereby modulating the output of ganglion cells responsive to color contrast. Images PMID:6199789

Stellate nonhereditary idiopathic foveomacular retinoschisis concomitant to exudative maculopathies

PubMed Central

Casalino, G; Upendran, M; Bandello, F; Chakravarthy, U

2016-01-01

Purpose To report the clinical course of patients presenting with stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) concomitant with exudative maculopathies. Methods Retrospective case series. Multimodal imaging findings, including spectral-domain optical coherence tomography (SD-OCT) were reviewed. Genetic testing for the RS1 gene was performed in one patient. Results We identified two female patients who fit the definition of SNIFR and presented with concomitant neovascular age-related macular degeneration (n-AMD). In both the patients, SD-OCT showed exudative macular features and splitting (bilateral in patient 1, unilateral in patient 2) of the outer plexiform layer (OPL) in the macula with no other evidence of hereditary or an acquired predisposing condition. Genetic testing excluded mutation of RS1 gene in patient 1. The fundi of both the patients showed characteristic signs of active choroidal neovascularization (CNV) and following anti-VEGF treatment, visual acuity improved and CNV-related exudative changes resolved. However, the split along the OPL remained unaltered. Conclusions SNIFR may be associated with n-AMD. It is important to recognise the presence of retinoschisis when there is other exudative pathology as the former may be misinterpreted as intraretinal fluid, prompting unnecessary treatment. PMID:26915743

Proliferating Cell Nuclear Antigen (PCNA) Regulates Primordial Follicle Assembly by Promoting Apoptosis of Oocytes in Fetal and Neonatal Mouse Ovaries

PubMed Central

Zhang, Yuanwei; Jiang, Xiaohua; Zhang, Huan; Ma, Tieliang; Zheng, Wei; Sun, Rui; Shen, Wei; Sha, Jiahao; Cooke, Howard J.; Shi, Qinghua

2011-01-01

Primordial follicles, providing all the oocytes available to a female throughout her reproductive life, assemble in perinatal ovaries with individual oocytes surrounded by granulosa cells. In mammals including the mouse, most oocytes die by apoptosis during primordial follicle assembly, but factors that regulate oocyte death remain largely unknown. Proliferating cell nuclear antigen (PCNA), a key regulator in many essential cellular processes, was shown to be differentially expressed during these processes in mouse ovaries using 2D-PAGE and MALDI-TOF/TOF methodology. A V-shaped expression pattern of PCNA in both oocytes and somatic cells was observed during the development of fetal and neonatal mouse ovaries, decreasing from 13.5 to 18.5 dpc and increasing from 18.5 dpc to 5 dpp. This was closely correlated with the meiotic prophase I progression from pre-leptotene to pachytene and from pachytene to diplotene when primordial follicles started to assemble. Inhibition of the increase of PCNA expression by RNA interference in cultured 18.5 dpc mouse ovaries strikingly reduced the apoptosis of oocytes, accompanied by down-regulation of known pro-apoptotic genes, e.g. Bax, caspase-3, and TNFα and TNFR2, and up-regulation of Bcl-2, a known anti-apoptotic gene. Moreover, reduced expression of PCNA was observed to significantly increase primordial follicle assembly, but these primordial follicles contained fewer guanulosa cells. Similar results were obtained after down-regulation by RNA interference of Ing1b, a PCNA-binding protein in the UV-induced apoptosis regulation. Thus, our results demonstrate that PCNA regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries. PMID:21253613

Primordial features and Planck polarization

NASA Astrophysics Data System (ADS)

Hazra, Dhiraj Kumar; Shafieloo, Arman; Smoot, George F.; Starobinsky, Alexei A.

2016-09-01

With the Planck 2015 Cosmic Microwave Background (CMB) temperature and polarization data, we search for possible features in the primordial power spectrum (PPS). We revisit the Wiggly Whipped Inflation (WWI) framework and demonstrate how generation of some particular primordial features can improve the fit to Planck data. WWI potential allows the scalar field to transit from a steeper potential to a nearly flat potential through a discontinuity either in potential or in its derivatives. WWI offers the inflaton potential parametrizations that generate a wide variety of features in the primordial power spectra incorporating most of the localized and non-local inflationary features that are obtained upon reconstruction from temperature and polarization angular power spectrum. At the same time, in a single framework it allows us to have a background parameter estimation with a nearly free-form primordial spectrum. Using Planck 2015 data, we constrain the primordial features in the context of Wiggly Whipped Inflation and present the features that are supported both by temperature and polarization. WWI model provides more than 13 improvement in χ2 fit to the data with respect to the best fit power law model considering combined temperature and polarization data from Planck and B-mode polarization data from BICEP and Planck dust map. We use 2-4 extra parameters in the WWI model compared to the featureless strict slow roll inflaton potential. We find that the differences between the temperature and polarization data in constraining background cosmological parameters such as baryon density, cold dark matter density are reduced to a good extent if we use primordial power spectra from WWI. We also discuss the extent of bispectra obtained from the best potentials in arbitrary triangular configurations using the BI-spectra and Non-Gaussianity Operator (BINGO).

Primordial features and Planck polarization

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

Hazra, Dhiraj Kumar; Smoot, George F.; Shafieloo, Arman

2016-09-01

With the Planck 2015 Cosmic Microwave Background (CMB) temperature and polarization data, we search for possible features in the primordial power spectrum (PPS). We revisit the Wiggly Whipped Inflation (WWI) framework and demonstrate how generation of some particular primordial features can improve the fit to Planck data. WWI potential allows the scalar field to transit from a steeper potential to a nearly flat potential through a discontinuity either in potential or in its derivatives. WWI offers the inflaton potential parametrizations that generate a wide variety of features in the primordial power spectra incorporating most of the localized and non-local inflationarymore » features that are obtained upon reconstruction from temperature and polarization angular power spectrum. At the same time, in a single framework it allows us to have a background parameter estimation with a nearly free-form primordial spectrum. Using Planck 2015 data, we constrain the primordial features in the context of Wiggly Whipped Inflation and present the features that are supported both by temperature and polarization. WWI model provides more than 13 improvement in χ{sup 2} fit to the data with respect to the best fit power law model considering combined temperature and polarization data from Planck and B-mode polarization data from BICEP and Planck dust map. We use 2-4 extra parameters in the WWI model compared to the featureless strict slow roll inflaton potential. We find that the differences between the temperature and polarization data in constraining background cosmological parameters such as baryon density, cold dark matter density are reduced to a good extent if we use primordial power spectra from WWI. We also discuss the extent of bispectra obtained from the best potentials in arbitrary triangular configurations using the BI-spectra and Non-Gaussianity Operator (BINGO).« less

Gap junctions are essential for murine primordial follicle assembly immediately before birth.

PubMed

Teng, Zhen; Wang, Chao; Wang, Yijing; Huang, Kun; Xiang, Xi; Niu, Wanbao; Feng, Lizhao; Zhao, Lihua; Yan, Hao; Zhang, Hua

2016-02-01

The reserve of primordial follicles determines the reproductive ability of the female mammal over its reproductive life. The primordial follicle is composed of two types of cells: oocytes and surrounding pre-granulosa cells. However, the underlying mechanism regulating primordial follicle assembly is largely undefined. In this study, we found that gap junction communication (GJC) established between the ovarian cells in the perinatal mouse ovary may be involved in the process. First, gap junction structures between the oocyte and surrounding pre-granulosa cells appear at about 19.0 dpc (days post coitum). As many as 12 gap junction-related genes are upregulated at birth, implying that a complex communication may exist between ovarian cells, because specifically silencing the genes of individual gap junction proteins, such as Gja1, Gja4 or both, has no influence on primordial follicle assembly. On the other hand, non-specific blockers of GJC, such as carbenoxolone (CBX) and 18α-glycyrrhetinic acid (AGA), significantly inhibit mouse primordial follicle assembly. We proved that the temporal window for establishment of GJC in the fetal ovary is from 19.5 dpc to 1 dpp (days postpartum). In addition, the expression of ovarian somatic cell (OSC)-specific genes, such as Notch2, Foxl2 and Irx3, was negatively affected by GJC blockers, whereas oocyte-related genes, such as Ybx2, Nobox and Sohlh1, were hardly affected, implying that the establishment of GJC during this period may be more important to OSCs than to oocytes. In summary, our results indicated that GJC involves in the mouse primordial follicle assembly process at a specific temporal window that needs Notch signaling cross-talking. © 2016 Society for Reproduction and Fertility.

Cosmic microwave background constraints on primordial black hole dark matter

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

Aloni, Daniel; Blum, Kfir; Flauger, Raphael, E-mail: daniel.aloni@weizmann.ac.il, E-mail: kfir.blum@weizmann.ac.il, E-mail: flauger@physics.ucsd.edu

We revisit cosmic microwave background (CMB) constraints on primordial black hole dark matter. Spectral distortion limits from COBE/FIRAS do not impose a relevant constraint. Planck CMB anisotropy power spectra imply that primordial black holes with m {sub BH}∼> 5 M {sub ⊙} are disfavored. However, this is susceptible to sizeable uncertainties due to the treatment of the black hole accretion process. These constraints are weaker than those quoted in earlier literature for the same observables.

Quantum standard clocks in the primordial trispectrum

NASA Astrophysics Data System (ADS)

Chen, Xingang; Zhen Chua, Wan; Guo, Yuxun; Wang, Yi; Xianyu, Zhong-Zhi; Xie, Tianyou

2018-05-01

We calculate the primordial trispectrum of curvature perturbation in quasi-single field inflation, with general sound speeds for both the inflaton and the massive scalar. Special attention is paid to various soft limits of the trispectrum, where the shape function shows characteristic oscillatory pattern (known as the quantum primordial standard clock signal) as a function of the momentum ratio. Our calculation is greatly simplified by using the "mixed propagator" developed under a diagrammatic representation of the in-in formalism.

Primordial prevention of cardiovascular disease among African-Americans: a social epidemiological perspective.

PubMed

James, S A

1999-12-01

The primordial prevention of cardiovascular disease (CVD) among African-Americans represents a formidable challenge for public health. This paper discusses the nature of this challenge, highlighting the role that economic and cultural factors play in shaping the distributions of major CVD risk factors among African-Americans. The paper concludes with specific suggestions for research. Data from recent national health surveys on black/white differences in major CVD risk factors like hypertension, obesity, cholesterol, cigarette smoking, and physical inactivity were reviewed for the purpose of identifying promising avenues for primordial prevention research among African-Americans. Cigarette smoking has a delayed onset among African-Americans compared to whites. Black/white differences in "vigorous" leisure-time physical activity (e.g., social dancing and team sports) are not apparent until around age 40. These findings have relevance for primordial prevention work in black communities since they suggest the existence of broad-based, health-relevant cultural norms which could support primordial prevention programs, such as regular physical activity, across the life cycle. CVD primordial prevention programs among African-Americans must be grounded in an understanding of how cultural values as well as economic conditions shape CVD risk factor distributions in this population. Ultimate success will depend on the strength of the partnerships that public health researchers, primary care providers, and community residents are able to build.

Nonthermal WIMPs and primordial black holes

NASA Astrophysics Data System (ADS)

Georg, Julian; Şengör, Gizem; Watson, Scott

2016-06-01

Nonthermal histories for the early universe have received notable attention as they are a rich source of phenomenology, while also being well motivated by top-down approaches to beyond the Standard Model physics. The early (pre-big bang nucleosynthesis) matter phase in these models leads to enhanced growth of density perturbations on sub-Hubble scales. Here, we consider whether primordial black hole formation associated with the enhanced growth is in conflict with existing observations. Such constraints depend on the tilt of the primordial power spectrum, and we find that nonthermal histories are tightly constrained in the case of a significantly blue spectrum. Alternatively, if dark matter is taken to be of nonthermal origin, we can restrict the primordial power spectrum on scales inaccessible to cosmic microwave background and large scale structure observations. We establish constraints for a wide range of scalar masses (reheat temperatures) with the most stringent bounds resulting from the formation of 1015 g black holes. These black holes would be evaporating today and are constrained by FERMI observations. We also consider whether the breakdown of the coherence of the scalar oscillations on subhorizon scales can lead to a Jean's pressure preventing black hole formation and relaxing our constraints. Our main conclusion is that primordial black hole constraints, combined with existing constraints on nonthermal weakly interacting massive particles, favor a primordial spectrum closer to scale invariance or a red tilted spectrum.

Rac1 modulates the formation of primordial follicles by facilitating STAT3-directed Jagged1, GDF9 and BMP15 transcription in mice

PubMed Central

Zhao, Lihua; Du, Xinhua; Huang, Kun; Zhang, Tuo; Teng, Zhen; Niu, Wanbao; Wang, Chao; Xia, Guoliang

2016-01-01

The size of the primordial follicle pool determines the reproductive potential of mammalian females, and establishment of the pool is highly dependent on specific genes expression. However, the molecular mechanisms by which the essential genes are regulated coordinately to ensure primordial follicle assembly remain a mystery. Here, we show that the small GTPase Rac1 plays an indispensable role in controlling the formation of primordial follicles in mouse ovary. Employing fetal mouse ovary organ culture system, we demonstrate that disruption of Rac1 retarded the breakdown of germline cell cysts while Rac1 overexpression accelerated the formation of primordial follicles. In addition, in vivo inhibitor injection resulted in the formation of multi-oocyte follicles. Subsequent investigation showed that Rac1 induced nuclear import of STAT3 by physical binding. In turn, nuclear STAT3 directly activated the transcription of essential oocyte-specific genes, including Jagged1, GDF9, BMP15 and Nobox. Further, GDF9 and BMP15 regulated the translation of Notch2 via mTORC1 activation in pregranulosa cells. Overexression or addition of Jagged1, GDF9 and BMP15 not only reversed the effect of Rac1 disruption, but also accelerated primordial follicle formation via Notch2 signaling activation. Collectively, these results indicate that Rac1 plays important roles as a key regulator in follicular assembly. PMID:27050391

The planarian nanos-like gene Smednos is expressed in germline and eye precursor cells during development and regeneration.

PubMed

Handberg-Thorsager, Mette; Saló, Emili

2007-05-01

Planarians are highly regenerative organisms with the ability to remake all their cell types, including the germ cells. The germ cells have been suggested to arise from totipotent neoblasts through epigenetic mechanisms. Nanos is a zinc-finger protein with a widely conserved role in the maintenance of germ cell identity. In this work, we describe the expression of a planarian nanos-like gene Smednos in two kinds of precursor cells namely, primordial germ cells and eye precursor cells, during both development and regeneration of the planarian Schmidtea mediterranea. In sexual planarians, Smednos is expressed in presumptive male primordial germ cells of embryos from stage 8 of embryogenesis and throughout development of the male gonads and in the female primordial germ cells of the ovary. Thus, upon hatching, juvenile planarians do possess primordial germ cells. In the asexual strain, Smednos is expressed in presumptive male and female primordial germ cells. During regeneration, Smednos expression is maintained in the primordial germ cells, and new clusters of Smednos-positive cells appear in the regenerated tissue. Remarkably, during the final stages of development (stage 8 of embryogenesis) and during regeneration of the planarian eye, Smednos is expressed in cells surrounding the differentiating eye cells, possibly corresponding to eye precursor cells. Our results suggest that similar genetic mechanisms might be used to control the differentiation of precursor cells during development and regeneration in planarians.

Cooling of the magma ocean due to accretional disruption of the surface insulating layer

NASA Technical Reports Server (NTRS)

Sasaki, Sho

1992-01-01

Planetary accretion has been considered as a process to heat planets. Some fraction of the kinetic energy of incoming planetesimals is trapped to heat the planetary interior (Kaula, 1979; Davies, 1984). Moreover, blanketing effect of a primary atmosphere (Hayashi et al., 1979; Sasaki, 1990) or a degassed atmosphere (Abe and Matsui, 1986; Zahnle et al., 1988) would raise the surface temperature of the Earth-size planets to be higher than the melting temperature. The primordial magma ocean was likely to be formed during accretion of terrestrial planets. In the magma ocean, if crystallized fractions were heavier than melt, they would sink. But if solidified materials were lighter than the melt (like anorthosite of the lunar early crust) they would float to form a solid shell surrounding the planet. (In an icy satellite, solidified water ice should easily float on liquid water because of its small density.) The surface solid lid would prevent efficient convective heat transfer and slow the interior cooling. Consider that the accretion of planetesimals still continues in this cooling stage. Shock disruption at planetesimal impact events may destroy the solid insulating layer. Even if the layer survives impacts, the surface layer is finally overturned by Rayleigh-Taylor instability, since accreting materials containing metals are heavier than the surface solidified lid of silicates.

Primordial random motions and angular momenta of galaxies and galaxy clusters.

NASA Technical Reports Server (NTRS)

Silk, J.; Lea, S.

1973-01-01

We study the decay of primordial random motions of galaxies and galaxy clusters in an expanding universe by solving a kinetic equation for the relaxation of differential energy spectra N(E, t). Systematic dissipative energy losses are included, involving gravitational drag by, and accretion of, intergalactic matter, as well as the effect of collisions with other systems. Formal and numerical solutions are described for two distinct modes of galaxy formation in a turbulent medium, corresponding to formation at a distinct epoch and to continuous formation of galaxies. We show that any primordial random motions of galaxies at the present epoch can amount to at most a few km/sec, and that collisions at early epochs can lead to the acquisition of significant amounts of primordial angular momentum.

Galaxy bias and primordial non-Gaussianity

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

Assassi, Valentin; Baumann, Daniel; Schmidt, Fabian, E-mail: assassi@ias.edu, E-mail: D.D.Baumann@uva.nl, E-mail: fabians@MPA-Garching.MPG.DE

2015-12-01

We present a systematic study of galaxy biasing in the presence of primordial non-Gaussianity. For a large class of non-Gaussian initial conditions, we define a general bias expansion and prove that it is closed under renormalization, thereby showing that the basis of operators in the expansion is complete. We then study the effects of primordial non-Gaussianity on the statistics of galaxies. We show that the equivalence principle enforces a relation between the scale-dependent bias in the galaxy power spectrum and that in the dipolar part of the bispectrum. This provides a powerful consistency check to confirm the primordial origin ofmore » any observed scale-dependent bias. Finally, we also discuss the imprints of anisotropic non-Gaussianity as motivated by recent studies of higher-spin fields during inflation.« less

Pregnancy in a woman with proportionate (primordial) dwarfism: a case report and literature review.

PubMed

Vance, C E; Desmond, M; Robinson, A; Johns, J; Zacharin, M; Savarirayan, R; König, K; Warrillow, S; Walker, S P

2012-09-01

Primordial dwarfism is a rare form of severe proportionate dwarfism which poses significant challenges in pregnancy. A 27-year-old with primordial dwarfism (height 97 cm, weight 22 kg) and coexisting morbidities of familial hypercholesterolaemia and hypertension presented to our unit. Early pregnancy was complicated by difficult blood pressure control, sinus tachycardia, biochemical hyperthyroidism and insulin-requiring gestational diabetes. Delivery was indicated at 24 weeks with uncontrollable hypertension, progressive renal impairment and intrauterine growth restriction. A caesarean section was performed under general anaesthesia, resulting in the delivery of a 486 g male infant. This case highlights the difficulties of managing pregnancy in a woman with primordial dwarfism. Her limited capacity to respond to the physiological demands of pregnancy created a life-threatening situation, culminating in profound preterm birth.

Searching for Primordial Black Holes in the Radio and X-Ray Sky.

PubMed

Gaggero, Daniele; Bertone, Gianfranco; Calore, Francesca; Connors, Riley M T; Lovell, Mark; Markoff, Sera; Storm, Emma

2017-06-16

We model the accretion of gas onto a population of massive primordial black holes in the Milky Way and compare the predicted radio and x-ray emission with observational data. We show that, under conservative assumptions on the accretion process, the possibility that O(10)M_{⊙} primordial black holes can account for all of the dark matter in the Milky Way is excluded at 5σ by a comparison with a Very Large Array radio catalog at 1.4 GHz and at ≃40σ by a comparison with a Chandra x-ray catalog (0.5-8 keV). We argue that this method can be used to identify such a population of primordial black holes with more sensitive future radio and x-ray surveys.

Tibet's window on primordial gravitational waves

NASA Astrophysics Data System (ADS)

Li, Hong; Li, Si-Yu; Liu, Yang; Li, Yong-Ping; Zhang, Xinmin

2018-02-01

The Ali Cosmic Microwave Background Polarization Telescope — currently under construction in the Ngari prefecture of Tibet — will search for primordial gravitational waves and probe the origin of the Universe.

Characterization of photoreceptor degeneration in the rhodopsin P23H transgenic rat line 2 using optical coherence tomography.

PubMed

Monai, Natsuki; Yamauchi, Kodai; Tanabu, Reiko; Gonome, Takayuki; Ishiguro, Sei-Ichi; Nakazawa, Mitsuru

2018-01-01

To characterize the optical coherence tomography (OCT) appearances of photoreceptor degeneration in the rhodopsin P23H transgenic rat (line 2) in relation to the histological, ultrastructural, and electroretinography (ERG) findings. Homozygous rhodopsin P23H transgenic albino rats (line 2, very-slow degeneration model) were employed. Using OCT (Micron IV®; Phoenix Research Labs, Pleasanton, CA, USA), the natural course of photoreceptor degeneration was recorded from postnatal day (P) 15 to P 287. The OCT images were qualitatively observed by comparing them to histological and ultrastructural findings at P 62 and P 169. In addition, each retinal layer was quantitatively analyzed longitudinally during degeneration, compared it to that observed in wild type Sprague-Dawley (SD) rats. The relationships between the ERG (full-field combined rod-cone response, 3.0 cds/m2 stimulation) findings and OCT images were also analyzed. In the qualitative study, the two layers presumably corresponding to the photoreceptor inner segment ellipsoid zone (EZ) and interdigitation zone (IZ) were identified in the P23H rat until PN day 32. However, the photoreceptor inner and outer segment (IS/OS) layer became diffusely hyperreflective on OCT after P 46, and the EZ and IZ zones could no longer be identified on OCT. In contrast, in the SD rats, the EZ and IZ were clearly distinguished until at least P 247. The ultrastructural study showed partial disarrangements of the photoreceptor outer segment discs in the P23H rats at P 62, although a light-microscopic histological study detected almost no abnormality in the outer segment. In the quantitative study, the outer retinal layer including the outer plexiform layer (OPL) and the outer nuclear layer (ONL) became significantly thinner in the P23H rats than in the SD rats after P 71. The thickness of the IS/OS layer was maintained in the P23H rats until P 130, and it became statistically thinner than in the SD rats at P 237. The longitudinal attenuation in the amplitude of the a- and b-waves of ERG was significantly correlated with the thickness of the combined OPL and ONL but not with that of the IS/OS layer. OCT showed the degenerated photoreceptor IS/OS layer in rhodopsin P23H transgenic rats (line 2) as a diffuse hyperreflective zone, even in the early stage, with the partially disarranged and destabilized OS discs recognizable by ultrastructural assessment but not by a histological study. The amplitude of the a- and b-waves mainly depends on the thickness of the OPL and ONL layer rather than the thickness of the photoreceptor IS/OS layer in P23H rats.

Bioorganic chemistry and the emergence of the first cell

NASA Technical Reports Server (NTRS)

Fox, S. W.

1977-01-01

It is suggested that the best way to study the evolution of cells from primordial compounds is to attempt to assemble a protocell, i.e., a primordial cell. Simulation of processes that occurred in archaic times would require inductive reasoning and constructionist techniques rather than the analytic approach in which cell components are separated and studied in isolation. Advantages to primordial life which would result from protocell formation are surveyed, and the proteinoid microsphere, a model of the protocell, is discussed. A photoreactive proteinoid is considered.

Trauma and daimonic reality in Ferenczi's later work.

PubMed

Kalsched, Donald

2003-09-01

Jung and Ferenczi made independent discoveries of an 'archaic' (Jung) or 'primordial' (Ferenczi) layer of the psyche that shone through the 'basic fault' in the psyche opened by childhood trauma. This paper explores those parallels through an extended vignette of Ferenczi's work with Elizabeth Severn, known as 'R. N.' in the Clinical Diary. A remarkable inner object known as 'Orpha' appeared in the patient's trauma experience and saved a seed of personality from total annihilation. Ferenczi's speculation about this 'daimonic' object is cited along with his discussion of a transpersonal immaterial reality that Orpha makes visible, and that links the patient's ego-experience with a spiritual/material unity not ordinarily available to consciousness.

Identification of protein kinase C α- and tyrosine hydroxylase-immunoreactive cells in the microbat retina.

PubMed

Park, Eun-Bee; Jeon, Joo-Yeong; Jeon, Chang-Jin

2018-05-09

A growing number of studies have revealed the functional neuroarchitecture of the microbat retina and suggested that microbats can see using their eyes. To better understand the organization of the microbat retina, quantitative analysis of protein kinase C alpha (PKCα)- and tyrosine hydroxylase (TH)-immunoreactive (IR) cells was conducted on the greater horseshoe bat (Rhinolophus ferrumequinum) retina. As a result, PKCα immunoreactivity was observed in rod bipolar cells, consistent with previous studies on other mammalian retinas. PKCα-IR cell distribution in the inner nuclear layer showed regional differences in density, with the highest density found in the nasal retina. The average density of PKCα-IR cells was 10,487±441 cells/mm2 (mean ± S.D.; n=4), with a total of 43,077±1,843 cells/retina. TH-IR cells in the Rhinolophus ferrumequinum retina could be classified into four types based on soma location and ramification in the inner plexiform layer: conventional amacrine, displaced amacrine, interplexiform, and intercalated cells. The majority of TH-IR cells were conventional amacrine cells. TH-IR cells were nonrandomly distributed at low density over the retina. The average density was 29.7±3.1 cells/mm2 (mean ± S.D.; n=3), with a total of 124.0±11.3 cells/retina. TH-IR processes showed varicosities and formed ring-like structures encircling AII amacrine cells. Our study provides the foundation for understanding the neurochemical architecture of the microbat retina and supports the notion that the eyes do play a role in the visual system of microbats.

Structural and functional assessment of macula to diagnose glaucoma.

PubMed

Rao, H L; Hussain, R S M; Januwada, M; Pillutla, L N; Begum, V U; Chaitanya, A; Senthil, S; Garudadri, C S

2017-04-01

PurposeTo compare the diagnostic abilities of structural (ganglion cell-inner plexiform layer (GCIPL) thickness measured using spectral domain optical coherence tomography (SDOCT)) and functional (visual sensitivities measured using standard automated perimetry (SAP) and microperimetry (MP)) assessments of macula in glaucoma.MethodsIn a prospective study, 46 control eyes (28 subjects) and 61 glaucoma eyes (46 patients) underwent visual sensitivity estimation at macula (central 10°) by SAP and MP, and GCIPL thickness measurement at macula by SDOCT. Glaucoma was diagnosed by experts based on the optic disc and retinal nerve fiber layer changes. Area under the receiver-operating characteristic (AUC) curves and sensitivities at 95% specificity were used to assess the diagnostic ability of visual sensitivity and GCIPL measurements at various macular sectors.ResultsAUCs of GCIPL parameters ranged between 0.58 and 0.79. AUCs of SAP and MP sensitivities ranged between 0.59 and 0.71, and 0.59 and 0.72, respectively. There were no statistically significant differences between the AUCs of corresponding sector measurements (P>0.10 for all comparisons). Sensitivities at 95% specificities ranged from 31-59% for GCIPL parameters, 16-34% for SAP, and 8-38% for MP parameters. Sensitivities were significantly better with GCIPL compared with SAP and MP parameters in diagnosing glaucoma. Inferotemporal, inferior, and superotemporal sector measurements of GCIPL and visual sensitivity showed the best abilities to diagnose glaucoma.ConclusionsComparing the diagnostic abilities of structural and functional tests at macula in glaucoma, GCIPL thickness measurements with SDOCT performed better than the visual sensitivity measurements by SAP and MP.

Macular ganglion cell imaging study: glaucoma diagnostic accuracy of spectral-domain optical coherence tomography.

PubMed

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

2013-07-01

We evaluated the diagnostic accuracy of macular ganglion cell-inner plexiform layer (GCIPL) measurements using a high-definition optical coherence tomography (Cirrus HD-OCT) ganglion cell analysis algorithm for detecting early and moderate-to-severe glaucoma. Totals of 119 normal subjects and 306 glaucoma patients (164 patients with early glaucoma and 142 with moderate-to-severe glaucoma) were enrolled from the Macular Ganglion Cell Imaging Study. Macular GCIPL, peripapillary retinal nerve fiber layer (RNFL) thickness, and optic nerve head (ONH) parameters were measured in each subject. Areas under the receiver operating characteristic curves (AUROCs) were calculated and compared. Based on the internal normative database, the sensitivity and specificity for detecting early and moderate-to-severe glaucoma were calculated. There was no statistically significant difference between the AUROCs for the best OCT parameters. For detecting early glaucoma, the sensitivity of the Cirrus GCIPL parameters ranged from 26.8% to 73.2% and that of the Cirrus RNFL parameters ranged from 6.1% to 61.6%. For the early glaucoma group, the best parameter from the GCIPL generally had a higher sensitivity than those of the RNFL and ONH parameters with comparable specificity (P < 0.05, McNemar's test). There were no significant differences between the AUROCs for Cirrus GCIPL, RNFL, and ONH parameters, indicating that these maps have similar diagnostic potentials for glaucoma. The minimum GCIPL showed better glaucoma diagnostic performance than the other parameters at comparable specificities. However, other GCIPL parameters showed performances comparable to those of the RNFL parameters.

Clinical Use of an Optical Coherence Tomography Linear Discriminant Function for Differentiating Glaucoma From Normal Eyes.

PubMed

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

2016-03-01

To determine and validate the diagnostic ability of a linear discriminant function (LDF) based on retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness obtained using high-definition optical coherence tomography (Cirrus HD-OCT) for discriminating between healthy controls and early glaucoma subjects. We prospectively selected 214 healthy controls and 152 glaucoma subjects (teaching set) and another independent sample of 86 healthy controls and 71 glaucoma subjects (validating set). Two scans, including 1 macular and 1 peripapillary RNFL scan, were obtained. After calculating the LDF in the teaching set using the binary logistic regression analysis, receiver operating characteristic curves were plotted and compared between the OCT-provided parameters and LDF in the validating set. The proposed LDF was 16.529-(0.132×superior RNFL)-(0.064×inferior RNFL)+(0.039×12 o'clock RNFL)+(0.038×1 o'clock RNFL)+(0.084×superior GCIPL)-(0.144×minimum GCIPL). The highest area under the receiver operating characteristic (AUROC) curve was obtained for LDF in both sets (AUROC=0.95 and 0.96). In the validating set, the LDF showed significantly higher AUROC than the best RNFL (inferior RNFL=0.91) and GCIPL parameter (minimum GCIPL=0.88). The LDF yielded a sensitivity of 93.0% at a fixed specificity of 85.0%. The LDF showed better diagnostic ability for differentiating between healthy and early glaucoma subjects than individual OCT parameters. A classification algorithm based on the LDF can be used in the OCT analysis for glaucoma diagnosis.

Automated segmentation of mouse OCT volumes (ASiMOV): Validation & clinical study of a light damage model.

PubMed

Antony, Bhavna Josephine; Kim, Byung-Jin; Lang, Andrew; Carass, Aaron; Prince, Jerry L; Zack, Donald J

2017-01-01

The use of spectral-domain optical coherence tomography (SD-OCT) is becoming commonplace for the in vivo longitudinal study of murine models of ophthalmic disease. Longitudinal studies, however, generate large quantities of data, the manual analysis of which is very challenging due to the time-consuming nature of generating delineations. Thus, it is of importance that automated algorithms be developed to facilitate accurate and timely analysis of these large datasets. Furthermore, as the models target a variety of diseases, the associated structural changes can also be extremely disparate. For instance, in the light damage (LD) model, which is frequently used to study photoreceptor degeneration, the outer retina appears dramatically different from the normal retina. To address these concerns, we have developed a flexible graph-based algorithm for the automated segmentation of mouse OCT volumes (ASiMOV). This approach incorporates a machine-learning component that can be easily trained for different disease models. To validate ASiMOV, the automated results were compared to manual delineations obtained from three raters on healthy and BALB/cJ mice post LD. It was also used to study a longitudinal LD model, where five control and five LD mice were imaged at four timepoints post LD. The total retinal thickness and the outer retina (comprising the outer nuclear layer, and inner and outer segments of the photoreceptors) were unchanged the day after the LD, but subsequently thinned significantly (p < 0.01). The retinal nerve fiber-ganglion cell complex and the inner plexiform layers, however, remained unchanged for the duration of the study.

Automated segmentation of mouse OCT volumes (ASiMOV): Validation & clinical study of a light damage model

PubMed Central

Lang, Andrew; Carass, Aaron; Prince, Jerry L.; Zack, Donald J.

2017-01-01

The use of spectral-domain optical coherence tomography (SD-OCT) is becoming commonplace for the in vivo longitudinal study of murine models of ophthalmic disease. Longitudinal studies, however, generate large quantities of data, the manual analysis of which is very challenging due to the time-consuming nature of generating delineations. Thus, it is of importance that automated algorithms be developed to facilitate accurate and timely analysis of these large datasets. Furthermore, as the models target a variety of diseases, the associated structural changes can also be extremely disparate. For instance, in the light damage (LD) model, which is frequently used to study photoreceptor degeneration, the outer retina appears dramatically different from the normal retina. To address these concerns, we have developed a flexible graph-based algorithm for the automated segmentation of mouse OCT volumes (ASiMOV). This approach incorporates a machine-learning component that can be easily trained for different disease models. To validate ASiMOV, the automated results were compared to manual delineations obtained from three raters on healthy and BALB/cJ mice post LD. It was also used to study a longitudinal LD model, where five control and five LD mice were imaged at four timepoints post LD. The total retinal thickness and the outer retina (comprising the outer nuclear layer, and inner and outer segments of the photoreceptors) were unchanged the day after the LD, but subsequently thinned significantly (p < 0.01). The retinal nerve fiber-ganglion cell complex and the inner plexiform layers, however, remained unchanged for the duration of the study. PMID:28817571

Phagocytosis of photoreceptor outer segments by transplanted human neural stem cells as a neuroprotective mechanism in retinal degeneration.

PubMed

Cuenca, Nicolás; Fernández-Sánchez, Laura; McGill, Trevor J; Lu, Bin; Wang, Shaomei; Lund, Raymond; Huhn, Stephen; Capela, Alexandra

2013-10-15

Transplantation of human central nervous system stem cells (HuCNS-SC) into the subretinal space of Royal College of Surgeons (RCS) rats preserves photoreceptors and visual function. To explore possible mechanism(s) of action underlying this neuroprotective effect, we performed a detailed morphologic and ultrastructure analysis of HuCNS-SC transplanted retinas. The HuCNS-SC were transplanted into the subretinal space of RCS rats. Histologic examination of the transplanted retinas was performed by light and electron microscopy. Areas of the retina adjacent to HuCNS-SC graft (treated regions) were analyzed and compared to control sections obtained from the same retina, but distant from the transplant site (untreated regions). The HuCNS-SC were detected as a layer of STEM 121 immunopositive cells in the subretinal space. In treated regions, preserved photoreceptor nuclei, as well as inner and outer segments were identified readily. In contrast, classic signs of degeneration were observed in the untreated regions. Interestingly, detailed ultrastructure analysis revealed a striking preservation of the photoreceptor-bipolar-horizontal cell synaptic contacts in the outer plexiform layer (OPL) of treated areas, in stark contrast with untreated areas. Finally, the presence of phagosomes and vesicles exhibiting the lamellar structure of outer segments also was detected within the cytosol of HuCNS-SC, indicating that these cells have phagocytic capacity in vivo. This study reveals the novel finding that preservation of specialized synaptic contacts between photoreceptors and second order neurons, as well as phagocytosis of photoreceptor outer segments, are potential mechanism(s) of HuCNS-SC transplantation, mediating functional rescue in retinal degeneration.

Involvement of Autophagic Pathway in the Progression of Retinal Degeneration in a Mouse Model of Diabetes.

PubMed

Piano, Ilaria; Novelli, Elena; Della Santina, Luca; Strettoi, Enrica; Cervetto, Luigi; Gargini, Claudia

2016-01-01

The notion that diabetic retinopathy (DR) is essentially a micro-vascular disease has been recently challenged by studies reporting that vascular changes are preceded by signs of damage and loss of retinal neurons. As to the mode by which neuronal death occurs, the evidence that apoptosis is the main cause of neuronal loss is far from compelling. The objective of this study was to investigate these controversies in a mouse model of streptozotocin (STZ) induced diabetes. Starting from 8 weeks after diabetes induction there was loss of rod but not of cone photoreceptors, together with reduced thickness of the outer and inner synaptic layers. Correspondingly, rhodopsin expression was downregulated and the scotopic electroretinogram (ERG) is suppressed. In contrast, cone opsin expression and photopic ERG response were not affected. Suppression of the scotopic ERG preceded morphological changes as well as any detectable sign of vascular alteration. Only sparse apoptotic figures were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and glia was not activated. The physiological autophagy flow was altered instead, as seen by increased LC3 immunostaining at the level of outer plexiform layer (OPL) and upregulation of the autophagic proteins Beclin-1 and Atg5. Collectively, our results show that the streptozotocin induced DR in mouse initiates with a functional loss of the rod visual pathway. The pathogenic pathways leading to cell death develop with the initial dysregulation of autophagy well before the appearance of signs of vascular damage and without strong involvement of apoptosis.

Involvement of Autophagic Pathway in the Progression of Retinal Degeneration in a Mouse Model of Diabetes

PubMed Central

Piano, Ilaria; Novelli, Elena; Della Santina, Luca; Strettoi, Enrica; Cervetto, Luigi; Gargini, Claudia

2016-01-01

The notion that diabetic retinopathy (DR) is essentially a micro-vascular disease has been recently challenged by studies reporting that vascular changes are preceded by signs of damage and loss of retinal neurons. As to the mode by which neuronal death occurs, the evidence that apoptosis is the main cause of neuronal loss is far from compelling. The objective of this study was to investigate these controversies in a mouse model of streptozotocin (STZ) induced diabetes. Starting from 8 weeks after diabetes induction there was loss of rod but not of cone photoreceptors, together with reduced thickness of the outer and inner synaptic layers. Correspondingly, rhodopsin expression was downregulated and the scotopic electroretinogram (ERG) is suppressed. In contrast, cone opsin expression and photopic ERG response were not affected. Suppression of the scotopic ERG preceded morphological changes as well as any detectable sign of vascular alteration. Only sparse apoptotic figures were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and glia was not activated. The physiological autophagy flow was altered instead, as seen by increased LC3 immunostaining at the level of outer plexiform layer (OPL) and upregulation of the autophagic proteins Beclin-1 and Atg5. Collectively, our results show that the streptozotocin induced DR in mouse initiates with a functional loss of the rod visual pathway. The pathogenic pathways leading to cell death develop with the initial dysregulation of autophagy well before the appearance of signs of vascular damage and without strong involvement of apoptosis. PMID:26924963

Glaucoma Diagnostic Capabilities of Foveal Avascular Zone Parameters Using Optical Coherence Tomography Angiography According to Visual Field Defect Location.

PubMed

Kwon, Junki; Choi, Jaewan; Shin, Joong Won; Lee, Jiyun; Kook, Michael S

2017-12-01

To assess the diagnostic ability of foveal avascular zone (FAZ) parameters to discriminate glaucomatous eyes with visual field defects (VFDs) in different locations (central vs. peripheral) from normal eyes. Totally, 125 participants were separated into 3 groups: normal (n=45), glaucoma with peripheral VFD (PVFD, n=45), and glaucoma with central VFD (CVFD, n=35). The FAZ area, perimeter, and circularity and parafoveal vessel density were calculated from optical coherence tomography angiography images. The diagnostic ability of the FAZ parameters and other structural parameters was determined according to glaucomatous VFD location. Associations between the FAZ parameters and central visual function were evaluated. A larger FAZ area and longer FAZ perimeter were observed in the CVFD group than in the PVFD and normal groups. The FAZ area, perimeter, and circularity were better in differentiating glaucomatous eyes with CVFDs from normal eyes [areas under the receiver operating characteristic curves (AUC), 0.78 to 0.88] than in differentiating PVFDs from normal eyes (AUC, 0.51 to 0.64). The FAZ perimeter had a similar AUC value to the circumpapillary retinal nerve fiber layer and macular ganglion cell-inner plexiform layer thickness for differentiating eyes with CVFDs from normal eyes (all P>0.05, the DeLong test). The FAZ area was significantly correlated with central visual function (β=-112.7, P=0.035, multivariate linear regression). The FAZ perimeter had good diagnostic capability in differentiating glaucomatous eyes with CVFDs from normal eyes, and may be a potential diagnostic biomarker for detecting glaucomatous patients with CVFDs.

Effects of hyperbaric oxygen on crystalline lens and retina in nicotine-exposed rats.

PubMed

Ari, Seyhmus; Nergiz, Yusuf; Cingü, Abdullah Kürşat; Atay, Ahmet Engin; Sahin, Alparslan; Cinar, Yasin; Caca, Ihsan

2013-03-01

To determine histopathological changes on crystalline lens and retina of rats after subcutaneous injection of nicotine and to examine the effects of hyperbaric oxygen (HBO) on these changes related to nicotine exposure. Twenty-eight female Sprague-Dawley rats were enrolled in the study and the rats were divided into four equal sized groups randomly (Group N: the rats exposed only to nicotine, group HB: the rats received only HBO, group N+HB: the rats that underwent to nicotine injection and subsequently received HBO, group C: the control group that neither exposed to nicotine nor received HBO). The rats were sacrificed by decapitation method and all were enucleated immediately after scarification. Tissue samples from crystalline lens, lens capsule, and the retina from the right eyes of the rats were examined by light microscopy. While the histological appearances of the retina and the lens was similar in group HB, group N+HB, and the control group; group N showed some pathological changes like decrement in the retinal ganglion cell density, atrophy of the retinal nerve fiber layer, congestion of the vessels in the optic nerve head, thinning of the internal plexiform layer, thinning of the lens capsule, and transformation of the anterior subcapsular epithelium into squamous epithelia. Subcutaneous injection of nicotine was found to be related with some pathological changes in the retina and lens of the Sprague-Dawley rats. However HBO caused no significant negative effect. Furthermore, the histopathological changes related to nicotine exposure in the lens and retina of the rats recovered by the application of HBO.

Early-onset, slow progression of cone photoreceptor dysfunction and degeneration in CNG channel subunit CNGB3 deficiency.

PubMed

Xu, Jianhua; Morris, Lynsie; Fliesler, Steven J; Sherry, David M; Ding, Xi-Qin

2011-06-01

To investigate the progression of cone dysfunction and degeneration in CNG channel subunit CNGB3 deficiency. Retinal structure and function in CNGB3(-/-) and wild-type (WT) mice were evaluated by electroretinography (ERG), lectin cytochemistry, and correlative Western blot analysis of cone-specific proteins. Cone and rod terminal integrity was assessed by electron microscopy and synaptic protein immunohistochemical distribution. Cone ERG amplitudes (photopic b-wave) in CNGB3(-/-) mice were reduced to approximately 50% of WT levels by postnatal day 15, decreasing further to approximately 30% of WT levels by 1 month and to approximately 20% by 12 months of age. Rod ERG responses (scotopic a-wave) were not affected in CNGB3(-/-) mice. Average CNGB3(-/-) cone densities were approximately 80% of WT levels at 1 month and declined slowly thereafter to only approximately 50% of WT levels by 12 months. Expression levels of M-opsin, cone transducin α-subunit, and cone arrestin in CNGB3(-/-) mice were reduced by 50% to 60% by 1 month and declined to 35% to 45% of WT levels by 9 months. In addition, cone opsin mislocalized to the outer nuclear layer and the outer plexiform layer in the CNGB3(-/-) retina. Cone and rod synaptic marker expression and terminal ultrastructure were normal in the CNGB3(-/-) retina. These findings are consistent with an early-onset, slow progression of cone functional defects and cone loss in CNGB3(-/-) mice, with the cone signaling deficits arising from disrupted phototransduction and cone loss rather than from synaptic defects.

Phenotypic characterization of X-linked retinoschisis: Clinical, electroretinography, and optical coherence tomography variables

PubMed Central

Neriyanuri, Srividya; Dhandayuthapani, Sudha; Arunachalam, Jayamuruga Pandian; Raman, Rajiv

2016-01-01

Aims: To study the phenotypic characteristics of X-linked retinoschisis (XLRS) and report the clinical, electroretinogram (ERG), and optical coherence tomography (OCT) variables in Indian eyes. Design: A retrospective study. Materials and Methods: Medical records of 21 patients with retinoschisis who were genetically confirmed to have RS1 mutation were reviewed. The phenotype characterization included the age of onset, best-corrected visual acuity, refractive error, fundus findings, OCT, and ERG. Statistical Analysis Used: Data from both the eyes were used for analysis. A P < 0.05 was set as statistical significance. Data were not normally distributed (P < 0.05, Shapiro wilk); hence, nonparametric tests were used for statistical analysis. Results: All were males whose mean age of presentation was 9 years. Visual acuity was moderately impaired (median 0.6 logMAR, interquartile range: 0.47, 1) in these eyes with a hyperopic refractive error of median +1.75 Ds (interquartile range: +0.50 Ds, +4.25 Ds). About 54.7% of the eyes had both foveal and peripheral schisis, isolated foveal schisis was seen in 28.5% of the eyes, and schisis with retinal detachment was seen in 16.6% of the eyes. The inner nuclear layer was found to be commonly involved in the schisis, followed by outer nuclear and plexiform layers as evident on OCT. On ERG, a- and b-wave amplitudes were significantly reduced in eyes with foveal and peripheral schisis when compared to the eyes with only foveal schisis (P < 0.05). Conclusions: XLRS has phenotypic heterogeneity as evident on OCT, ERG, and clinical findings. PMID:27609164

What does the fine-scale petrography of IDPs reveal about grain formation and evolution in the early solar system?

NASA Technical Reports Server (NTRS)

Bradley, John

1994-01-01

The 'pyroxene' interplanetary dust particles (IDP's) may be the best samples for investigation of primordial grain-forming reactions because they appear to have experienced negligible post-accretional alteration. They are likely to continue to yield information about gas-to-solid condensation and other grain-forming reactions that may have occurred either in the solar nebular or presolar interstellar environments. An immediate challenge lies in understanding the nanometer-scale petrography of the ultrafine-grained aggregates in 'pyroxene' IDP's. Whether these aggregates contain components from diverse grain-forming environments may ultimately be answered by systematic petrographic studies using electron microscopes capable of high spatial resolution microanalysis. It may be more difficult to decipher evidence of grain formation and evolution in 'olivine' and 'layer silicate' IDP's because they appear to have experienced post-accretional alteration. Most of the studied 'olivine' IDPs have been subjected to heating and equilibration, perhaps during atmospheric entry, while the 'layer silicate' IDP's have experienced aqueous alteration.

Early lunar petrogenesis, oceanic and extraoceanic

NASA Technical Reports Server (NTRS)

Warren, P. H.; Wasson, J. T.

1980-01-01

An attempt is made to ascertain which (if any) pristine nonmare rocks, other than KREEPy ones, are not cumulates from the magma ocean. It is noted that the only pristine rocks having bulk densities low enough to have formed by floating above the magma ocean are the ferroan anorthosites, which are easily recognizable as a discrete subset of pristine rocks in general, on the basis of mineral composition relationships. The other class of pristine nonmare rocks, the Mg-rich rocks, did not form from the same magma that produced the ferroan anorthosites. It is suggested that they were formed in layered noritic-troctolitic plutons. These plutons, it is noted, were apparently intruded at, or slightly above, the boundary between the floated ferroan anorthosite crust and the underlying complementary mafic cumulates. It is thought that the parental magmas of the plutons may have arisen by partial melting of either deep mafic cumulates from the magma ocean or a still deeper, undifferentiated primordial layer that was not molten during the magma ocean period.

Light sterile neutrinos and inflationary freedom

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

Gariazzo, S.; Giunti, C.; Laveder, M., E-mail: gariazzo@to.infn.it, E-mail: giunti@to.infn.it, E-mail: laveder@pd.infn.it

2015-04-01

We perform a cosmological analysis in which we allow the primordial power spectrum of scalar perturbations to assume a shape that is different from the usual power-law predicted by the simplest models of cosmological inflation. We parameterize the free primordial power spectrum with a ''piecewise cubic Hermite interpolating polynomial'' (PCHIP). We consider a 3+1 neutrino mixing model with a sterile neutrino having a mass at the eV scale, which can explain the anomalies observed in short-baseline neutrino oscillation experiments. We find that the freedom of the primordial power spectrum allows to reconcile the cosmological data with a fully thermalized sterilemore » neutrino in the early Universe. Moreover, the cosmological analysis gives us some information on the shape of the primordial power spectrum, which presents a feature around the wavenumber k=0.002 Mpc{sup −1}.« less

Mechanisms and pathways of growth failure in primordial dwarfism.

PubMed

Klingseisen, Anna; Jackson, Andrew P

2011-10-01

The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth.

Pregnancy in a woman with proportionate (primordial) dwarfism: a case report and literature review

PubMed Central

Vance, C E; Desmond, M; Robinson, A; Johns, J; Zacharin, M; Savarirayan, R; König, K; Warrillow, S; Walker, S P

2012-01-01

Primordial dwarfism is a rare form of severe proportionate dwarfism which poses significant challenges in pregnancy. A 27-year-old with primordial dwarfism (height 97 cm, weight 22 kg) and coexisting morbidities of familial hypercholesterolaemia and hypertension presented to our unit. Early pregnancy was complicated by difficult blood pressure control, sinus tachycardia, biochemical hyperthyroidism and insulin-requiring gestational diabetes. Delivery was indicated at 24 weeks with uncontrollable hypertension, progressive renal impairment and intrauterine growth restriction. A caesarean section was performed under general anaesthesia, resulting in the delivery of a 486 g male infant. This case highlights the difficulties of managing pregnancy in a woman with primordial dwarfism. Her limited capacity to respond to the physiological demands of pregnancy created a life-threatening situation, culminating in profound preterm birth. PMID:27582869

Selections from 2016: Primordial Black Holes as Dark Matter

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2016-12-01

Editors note:In these last two weeks of 2016, well be looking at a few selections that we havent yet discussed on AAS Nova from among the most-downloaded paperspublished in AAS journals this year. The usual posting schedule will resume after the AAS winter meeting.LIGO Gravitational Wave Detection, Primordial Black Holes, and the Near-IR Cosmic Infrared Background AnisotropiesPublished May2016Main takeaway:A study by Alexander Kashlinsky (NASA Goddard SFC) proposes that the cold dark matter that makes up the majority of the universes matter may be made of black holes. These black holes, Kashlinsky suggests, are primordial: they collapsed directly from dense regions of the universe soon after the Big Bang.Why its interesting:This model would simultaneously explain several observations. In particular, we see similarities in patterns between the cosmic infrared and X-ray backgrounds. This would make sense if accretion onto primordial black holes in halos produced the X-ray background in the same regions where the first stars also formed, producing the infrared background.What this means for current events:In Kashlinskys model, primordial black holes would occasionally form binary pairs and eventually spiral in and merge. The release of energy from such an event would then be observable by gravitational-wave detectors. Could the gravitational-wave signal that LIGO detected last year have been two primordial black holes merging? More observations will be needed to find out.CitationA. Kashlinsky 2016 ApJL 823 L25. doi:10.3847/2041-8205/823/2/L25

Gain and Loss of Photosynthetic Membranes during Plastid Differentiation in the Shoot Apex of Arabidopsis[W

PubMed Central

Charuvi, Dana; Kiss, Vladimir; Nevo, Reinat; Shimoni, Eyal; Adam, Zach; Reich, Ziv

2012-01-01

Chloroplasts of higher plants develop from proplastids, which are undifferentiated plastids that lack photosynthetic (thylakoid) membranes. In flowering plants, the proplastid-chloroplast transition takes place at the shoot apex, which consists of the shoot apical meristem (SAM) and the flanking leaf primordia. It has been believed that the SAM contains only proplastids and that these become chloroplasts only in the primordial leaves. Here, we show that plastids of the SAM are neither homogeneous nor necessarily null. Rather, their developmental state varies with the specific region and/or layer of the SAM in which they are found. Plastids throughout the L1 and L3 layers of the SAM possess fairly developed thylakoid networks. However, many of these plastids eventually lose their thylakoids during leaf maturation. By contrast, plastids at the central, stem cell–harboring region of the L2 layer of the SAM lack thylakoid membranes; these appear only at the periphery, near the leaf primordia. Thus, plastids in the SAM undergo distinct differentiation processes that, depending on their lineage and position, lead to either development or loss of thylakoid membranes. These processes continue along the course of leaf maturation. PMID:22438022

De-adhesion dynamics of melanoma cells from brain endothelial layer.

PubMed

Varga, Béla; Domokos, Réka Anita; Fazakas, Csilla; Wilhelm, Imola; Krizbai, István A; Szegletes, Zsolt; Gergely, Csilla; Váró, György; Végh, Attila G

2018-03-01

Metastasis formation is a complex and not entirely understood process. The poorest prognosis and the most feared complications are associated to brain metastases. Melanoma derived brain metastases show the highest prevalence. Due to the lack of classical lymphatic drainage, in the process of brain metastases formation the haematogenous route is of primordial importance. The first and crucial step in this multistep process is the establishment of firm adhesion between the blood travelling melanoma cells and the tightly connected layer of the endothelium, which is the fundamental structure of the blood-brain barrier. This study compares the de-adhesion properties and dynamics of three melanoma cells types (WM35, A2058 and A375) to a confluent layer of brain micro-capillary endothelial cells. Cell type dependent adhesion characteristics are presented, pointing towards the existence of metastatic potential related nanomechanical aspects. Apparent mechanical properties such as elasticity, maximal adhesion force, number, size and distance of individual rupture events showed altered values pointing towards cell type dependent aspects. Our results underline the importance of mechanical details in case of intercellular interactions. Nevertheless, it suggests that in adequate circumstances elastic and adhesive characterizations might be used as biomarkers. Copyright © 2017. Published by Elsevier B.V.

Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism.

PubMed

Shaheen, Ranad; Abdel-Salam, Ghada M H; Guy, Michael P; Alomar, Rana; Abdel-Hamid, Mohamed S; Afifi, Hanan H; Ismail, Samira I; Emam, Bayoumi A; Phizicky, Eric M; Alkuraya, Fowzan S

2015-09-28

Primordial dwarfism is a state of extreme prenatal and postnatal growth deficiency, and is characterized by marked clinical and genetic heterogeneity. Two presumably unrelated consanguineous families presented with an apparently novel form of primordial dwarfism in which severe growth deficiency is accompanied by distinct facial dysmorphism, brain malformation (microcephaly, agenesis of corpus callosum, and simplified gyration), and severe encephalopathy with seizures. Combined autozygome/exome analysis revealed a novel missense mutation in WDR4 as the likely causal variant. WDR4 is the human ortholog of the yeast Trm82, an essential component of the Trm8/Trm82 holoenzyme that effects a highly conserved and specific (m(7)G46) methylation of tRNA. The human mutation and the corresponding yeast mutation result in a significant reduction of m(7)G46 methylation of specific tRNA species, which provides a potential mechanism for primordial dwarfism associated with this lesion, since reduced m(7)G46 modification causes a growth deficiency phenotype in yeast. Our study expands the number of biological pathways underlying primordial dwarfism and adds to a growing list of human diseases linked to abnormal tRNA modification.

Age-standardized incidence rates of primordial cyst (keratocyst) on the Witwatersrand.

PubMed

Rachanis, C C; Shear, M

1978-11-01

Cases of primordial cysts derived from the records of all the hospital pathology departments and private pathology practices on the Witwatersrand, were recorded for the 10-year period 1965-74. The population at risk (1970 census) was 974,390 Whites and 1,567,280 Blacks. Age-specific morbidity rates for each sex and race were calculated, as well as age-standardized incidence rates standardized against African, World and European standard populations. The age-standardized incidence rates for primordial cysts, standardized against a World standard population, per million per year are 0.61, 0, 4.86 and 3.50 for Black males and females and White males and females, respectively. In the population at risk, primordial cysts are much more common in Whites than in Blacks, the incidence being eight times higher in White males than in Black males. The present study confirms that there is a bimodal age distribution but with a higher incidence of the cyst in the age group 50-64 years than previously suspected. This may be either because a substantial number of cases remain undiagnosed for many years or because there are two groups of primordial cyst: one which is triggered in young patients and the other in older patients.

FORMING CHONDRITES IN A SOLAR NEBULA WITH MAGNETICALLY INDUCED TURBULENCE

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

Hasegawa, Yasuhiro; Turner, Neal J.; Masiero, Joseph

Chondritic meteorites provide valuable opportunities to investigate the origins of the solar system. We explore impact jetting as a mechanism of chondrule formation and subsequent pebble accretion as a mechanism of accreting chondrules onto parent bodies of chondrites, and investigate how these two processes can account for the currently available meteoritic data. We find that when the solar nebula is ≤5 times more massive than the minimum-mass solar nebula at a ≃ 2–3 au and parent bodies of chondrites are ≤10{sup 24} g (≤500 km in radius) in the solar nebula, impact jetting and subsequent pebble accretion can reproduce a number ofmore » properties of the meteoritic data. The properties include the present asteroid belt mass, the formation timescale of chondrules, and the magnetic field strength of the nebula derived from chondrules in Semarkona. Since this scenario requires a first generation of planetesimals that trigger impact jetting and serve as parent bodies to accrete chondrules, the upper limit of parent bodies’ masses leads to the following implications: primordial asteroids that were originally ≥10{sup 24} g in mass were unlikely to contain chondrules, while less massive primordial asteroids likely had a chondrule-rich surface layer. The scenario developed from impact jetting and pebble accretion can therefore provide new insights into the origins of the solar system.« less

A Novel View of the Adult Stem Cell Compartment From the Perspective of a Quiescent Population of Very Small Embryonic-Like Stem Cells.

PubMed

Ratajczak, Mariusz Z; Ratajczak, Janina; Suszynska, Malwina; Miller, Donald M; Kucia, Magda; Shin, Dong-Myung

2017-01-06

Evidence has accumulated that adult hematopoietic tissues and other organs contain a population of dormant stem cells (SCs) that are more primitive than other, already restricted, monopotent tissue-committed SCs (TCSCs). These observations raise several questions, such as the developmental origin of these cells, their true pluripotent or multipotent nature, which surface markers they express, how they can be efficiently isolated from adult tissues, and what role they play in the adult organism. The phenotype of these cells and expression of some genes characteristic of embryonic SCs, epiblast SCs, and primordial germ cells suggests their early-embryonic deposition in developing tissues as precursors of adult SCs. In this review, we will critically discuss all these questions and the concept that small dormant SCs related to migratory primordial germ cells, described as very small embryonic-like SCs, are deposited during embryogenesis in bone marrow and other organs as a backup population for adult tissue-committed SCs and are involved in several processes related to tissue or organ rejuvenation, aging, and cancerogenesis. The most recent results on successful ex vivo expansion of human very small embryonic-like SC in chemically defined media free from feeder-layer cells open up new and exciting possibilities for their application in regenerative medicine. © 2017 American Heart Association, Inc.

Germline regeneration: the worms' turn.

PubMed

Weisblat, David A

2006-06-20

Asexual reproduction in the annelid Enchytraeus japonensis entails the regeneration of primordial germ cells from body parts that lack gonads. New primordial germ cells arise from piwi-expressing germline stem cells that are distinct from somatic stem cells.

Primordial lithium and the standard model(s)

NASA Technical Reports Server (NTRS)

Deliyannis, Constantine P.; Demarque, Pierre; Kawaler, Steven D.; Romanelli, Paul; Krauss, Lawrence M.

1989-01-01

The results of new theoretical work on surface Li-7 and Li-6 evolution in the oldest halo stars are presented, along with a new and refined analysis of the predicted primordial Li abundance resulting from big-bang nucleosynthesis. This makes it possible to determine the constraints which can be imposed on cosmology using primordial Li and both standard big-bang and stellar-evolution models. This leads to limits on the baryon density today of 0.0044-0.025 (where the Hubble constant is 100h km/sec Mpc) and imposes limitations on alternative nucleosynthesis scenarios.

Microcephalic osteodysplastic primordial dwarfism, with the fascinating history of "Mademoiselle Crachami".

PubMed

Bozkaya, O Giray

2013-01-01

This review critically examines the findings which characterize the dysmorphic, radiologic and behavioral phenotype of Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) and has an historical perspective on it. MOPD is a group of primordial dwarfism syndromes with prenatal onset growth retardation, a typical craniofacial appearance and behavioral phenotype. In 1959, Mann and Russell have described the first case in a detailed report, and named "microcephalic midget of extreme type". In their report; based on historical records and a small painting, they pointed "Mademoiselle Crachami" as the oldest known case.

Stability issues of nonlocal gravity during primordial inflation

NASA Astrophysics Data System (ADS)

Belgacem, Enis; Cusin, Giulia; Foffa, Stefano; Maggiore, Michele; Mancarella, Michele

2018-01-01

We study the cosmological evolution of some nonlocal gravity models, when the initial conditions are set during a phase of primordial inflation. We examine in particular three models, the so-called RT, RR and Δ4 models, previously introduced by our group. We find that, during inflation, the RT model has a viable background evolution, but at the level of cosmological perturbations develops instabilities that make it nonviable. In contrast, the RR and Δ4 models have a viable evolution even when their initial conditions are set during a phase of primordial inflation.

Implications of a primordial origin for the dispersion in D/H in quasar absorption systems

PubMed Central

Copi, Craig J.; Olive, Keith A.; Schramm, David N.

1998-01-01

We explore the difficulties with a primordial origin of variations of D/H in quasar absorption systems. In particular we examine options such as a very large-scale inhomogeneity in the baryon content of the universe. We show that very large-scale (much larger than 1 Mpc) isocurvature perturbations are excluded by current cosmic microwave background observations. Smaller-scale ad hoc perturbations (∼1 Mpc) still may lead to a large dispersion in primordial abundances but are subject to other constraints. PMID:9501162

Implications of a primordial origin for the dispersion in D/H in quasar absorption systems.

PubMed

Copi, C J; Olive, K A; Schramm, D N

1998-03-17

We explore the difficulties with a primordial origin of variations of D/H in quasar absorption systems. In particular we examine options such as a very large-scale inhomogeneity in the baryon content of the universe. We show that very large-scale (much larger than 1 Mpc) isocurvature perturbations are excluded by current cosmic microwave background observations. Smaller-scale ad hoc perturbations (approximately 1 Mpc) still may lead to a large dispersion in primordial abundances but are subject to other constraints.

The mammalian neocortex new pyramidal neuron: a new conception.

PubMed

Marín-Padilla, Miguel

2014-01-06

The new cerebral cortex (neocortex) and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities while essentially using analogous anatomical and neural makeups. The human neocortex starts to develop in 6-week-old embryos with the establishment of a primordial cortical organization, which resembles the primitive cortices of amphibian and reptiles. From the 8th to the 15th week of age, new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divides its components into those above it (neocortex first layer) and those below it (neocortex subplate zone). From the 16th week of age to birth and postnatally, the new pyramidal neurons continue to elongate functionally their apical dendrite by adding synaptic membrane to incorporate the needed sensory information for operating its developing motor activities. The new pyramidal neuron' distinguishing feature is the capacity of elongating anatomically and functionally its apical dendrite (its main receptive surface) without losing its original attachment to first layer or the location of its soma and, hence, retaining its essential nature. The number of pyramidal cell functional strata established in the motor cortex increases and reflects each mammalian species motor capabilities: the hedgehog needs two pyramidal cell functional strata to carry out all its motor activities, the mouse 3, cat 4, primates 5 and humans 6. The presence of six pyramidal cell functional strata distinguish the human motor cortex from that of others primates. Homo sapiens represent a new evolutionary stage that have transformed his primate brain for operating his unique motor capabilities, such as speaking, writing, painting, sculpturing and thinking as a premotor activity. Words used in language are the motor expression of thoughts and represent sounds produced by maneuvering the column of expiratory air by coordinated motor quivering as it passes through the larynx, pharynx, mouth, tongue, and lips. Homo sapiens cerebrum has developed new motor centers to communicate mental thoughts (and/or intention) through motor actions.

Europa's Crust and Ocean: Origin, Composition, and the Prospects for Life

USGS Publications Warehouse

Kargel, J.S.; Kaye, J.Z.; Head, J. W.; Marion, G.M.; Sassen, R.; Crowley, J.K.; Ballesteros, O.P.; Grant, S.A.; Hogenboom, D.L.

2000-01-01

We have considered a wide array of scenarios for Europa's chemical evolution in an attempt to explain the presence of ice and hydrated materials on its surface and to understand the physical and chemical nature of any ocean that may lie below. We postulate that, following formation of the jovian system, the europan evolutionary sequence has as its major links: (a) initial carbonaceous chondrite rock, (b) global primordial aqueous differentiation and formation of an impure primordial hydrous crust, (c) brine evolution and intracrustal differentiation, (d) degassing of Europa's mantle and gas venting, (e) hydrothermal processes, and (f) chemical surface alteration. Our models were developed in the context of constraints provided by Galileo imaging, near infrared reflectance spectroscopy, and gravity and magnetometer data. Low-temperature aqueous differentiation from a carbonaceous CI or CM chondrite precursor, without further chemical processing, would result in a crust/ocean enriched in magnesium sulfate and sodium sulfate, consistent with Galileo spectroscopy. Within the bounds of this simple model, a wide range of possible layered structures may result; the final state depends on the details of intracrustal differentiation. Devolatilization of the rocky mantle and hydrothermal brine reactions could have produced very different ocean/crust compositions, e.g., an ocean/crust of sodium carbonate or sulfuric acid, or a crust containing abundant clathrate hydrates. Realistic chemical-physical evolution scenarios differ greatly in detailed predictions, but they generally call for a highly impure and chemically layered crust. Some of these models could lead also to lateral chemical heterogeneities by diapiric upwellings and/or cryovolcanism. We describe some plausible geological consequences of the physical-chemical structures predicted from these scenarios. These predicted consequences and observed aspects of Europa's geology may serve as a basis for further analys is and discrimination among several alternative scenarios. Most chemical pathways could support viable ecosystems based on analogy with the metabolic and physiological versatility of terrestrial microorganisms. ?? 2000 Academic Press.

Proliferation in culture of primordial germ cells derived from embryonic stem cell: induction by retinoic acid.

PubMed

Makoolati, Zohreh; Movahedin, Mansoureh; Forouzandeh-Moghadam, Mehdi

2016-12-01

An in vitro system that supports primordial germ cells (PGCs) survival and proliferation is useful for enhancement of these cells and efficient transplantation in infertility disorders. One approach is cultivation of PGCs under proper conditions that allow self-renewal and proliferation of PGCs. For this purpose, we compared the effects of different concentrations of retinoic acid (RA), and the effect of PGCs co-culture (Co-C) with SIM mouse embryo-derived thioguanine- and ouabain-resistant (STO) cells on the proliferation of embryonic stem cells (ESCs)-derived PGCs. One-day-old embryoid body (EB) was cultured for 4 days in simple culture system in the presence of 5 ng/ml bone morphogenetic protein-4 (BMP4) (SCB group) for PGC induction. For PGC enrichment, ESCs-derived germ cells were cultured for 7 days in the presence of different doses (0-5  μM) of RA, both in the simple and STO Co-C systems. At the end of the culture period, viability and proliferation rates were assessed and expression of mouse vasa homologue (Mvh),  α6 integrin,  β1 integrin, stimulated by retinoic acid 8 (Stra8) and piwi (Drosophila)-like 2 (Piwil2) was evaluated using quantitative PCR. Also, the inductive effects were investigated immunocytochemically with Mvh and cadherin1 (CDH1) on the selected groups. Immunocytochemistry/PCR results showed higher expression of Mvh, the PGC-specific marker, in 3  μM RA concentrations on the top of the STO feeder layer. Meanwhile, assessment of the Stra8 mRNA and CDH1 protein, the specific makers for spermatogonia, showed no significant differences between groups. Based on the results, it seems that in the presence of 3 μM RA on top of the STO feeder layer cells, the majority of the cells transdifferentiated into germ cells were PGCs. © 2016 The Author(s).

Estimation of primordial spectrum with post-WMAP 3-year data

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

Shafieloo, Arman; Souradeep, Tarun

2008-07-15

In this paper we implement an improved (error-sensitive) Richardson-Lucy deconvolution algorithm on the measured angular power spectrum from the Wilkinson Microwave Anisotropy Probe (WMAP) 3 year data to determine the primordial power spectrum assuming different points in the cosmological parameter space for a flat {lambda}CDM cosmological model. We also present the preliminary results of the cosmological parameter estimation by assuming a free form of the primordial spectrum, for a reasonably large volume of the parameter space. The recovered spectrum for a considerably large number of the points in the cosmological parameter space has a likelihood far better than a 'bestmore » fit' power law spectrum up to {delta}{chi}{sub eff}{sup 2}{approx_equal}-30. We use discrete wavelet transform (DWT) for smoothing the raw recovered spectrum from the binned data. The results obtained here reconfirm and sharpen the conclusion drawn from our previous analysis of the WMAP 1st year data. A sharp cut off around the horizon scale and a bump after the horizon scale seem to be a common feature for all of these reconstructed primordial spectra. We have shown that although the WMAP 3 year data prefers a lower value of matter density for a power law form of the primordial spectrum, for a free form of the spectrum, we can get a very good likelihood to the data for higher values of matter density. We have also shown that even a flat cold dark matter model, allowing a free form of the primordial spectrum, can give a very high likelihood fit to the data. Theoretical interpretation of the results is open to the cosmology community. However, this work provides strong evidence that the data retains discriminatory power in the cosmological parameter space even when there is full freedom in choosing the primordial spectrum.« less

Anisotropic tensor power spectrum at interferometer scales induced by tensor squeezed non-Gaussianity

NASA Astrophysics Data System (ADS)

Ricciardone, Angelo; Tasinato, Gianmassimo

2018-02-01

We develop a scenario of inflation with spontaneously broken time and space diffeomorphisms, with distinctive features for the primordial tensor modes. Inflationary tensor fluctuations are not conserved outside the horizon, and can acquire a mass during the inflationary epoch. They can evade the Higuchi bound around de Sitter space, thanks to interactions with the fields driving expansion. Correspondingly, the primordial stochastic gravitational wave background (SGWB) is characterised by a tuneable scale dependence, and can be detectable at interferometer scales. In this set-up, tensor non-Gaussianity can be parametrically enhanced in the squeezed limit. This induces a coupling between long and short tensor modes, leading to a specific quadrupolar anisotropy in the primordial SGWB spectrum, which can be used to build estimators for tensor non-Gaussianity. We analyse how our inflationary system can be tested with interferometers, also discussing how an interferometer can be sensitive to a primordial anisotropic SGWB.

Primordial black holes for the LIGO events in the axionlike curvaton model

NASA Astrophysics Data System (ADS)

Ando, Kenta; Inomata, Keisuke; Kawasaki, Masahiro; Mukaida, Kyohei; Yanagida, Tsutomu T.

2018-06-01

We review primordial black hole (PBH) formation in the axionlike curvaton model and investigate whether PBHs formed in this model can be the origin of the gravtitational wave (GW) signals detected by the Advanced LIGO. In this model, small-scale curvature perturbations with large amplitude are generated, which is essential for PBH formation. On the other hand, large curvature perturbations also become a source of primordial GWs by their second-order effects. Severe constraints are imposed on such GWs by pulsar timing array (PTA) experiments. We also check the consistency of the model with these constraints. In this analysis, it is important to take into account the effect of non-Gaussianity, which is generated easily in the curvaton model. We see that, if there are non-Gaussianities, the fixed amount of PBHs can be produced with a smaller amplitude of the primordial power spectrum.

SPRAI: coupling of radiative feedback and primordial chemistry in moving mesh hydrodynamics

NASA Astrophysics Data System (ADS)

Jaura, O.; Glover, S. C. O.; Klessen, R. S.; Paardekooper, J.-P.

2018-04-01

In this paper, we introduce a new radiative transfer code SPRAI (Simplex Photon Radiation in the Arepo Implementation) based on the SIMPLEX radiation transfer method. This method, originally used only for post-processing, is now directly integrated into the AREPO code and takes advantage of its adaptive unstructured mesh. Radiated photons are transferred from the sources through the series of Voronoi gas cells within a specific solid angle. From the photon attenuation, we derive corresponding photon fluxes and ionization rates and feed them to a primordial chemistry module. This gives us a self-consistent method for studying dynamical and chemical processes caused by ionizing sources in primordial gas. Since the computational cost of the SIMPLEX method does not scale directly with the number of sources, it is convenient for studying systems such as primordial star-forming haloes that may form multiple ionizing sources.

Standard Clock in primordial density perturbations and cosmic microwave background

NASA Astrophysics Data System (ADS)

Chen, Xingang; Namjoo, Mohammad Hossein

2014-12-01

Standard Clocks in the primordial epoch leave a special type of features in the primordial perturbations, which can be used to directly measure the scale factor of the primordial universe as a function of time a (t), thus discriminating between inflation and alternatives. We have started to search for such signals in the Planck 2013 data using the key predictions of the Standard Clock. In this Letter, we summarize the key predictions of the Standard Clock and present an interesting candidate example in Planck 2013 data. Motivated by this candidate, we construct and compute full Standard Clock models and use the more complete prediction to make more extensive comparison with data. Although this candidate is not yet statistically significant, we use it to illustrate how Standard Clocks appear in Cosmic Microwave Background (CMB) and how they can be further tested by future data. We also use it to motivate more detailed theoretical model building.

Mechanisms and pathways of growth failure in primordial dwarfism

PubMed Central

Klingseisen, Anna; Jackson, Andrew P.

2011-01-01

The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth. PMID:21979914

Influences of the inner retinal sublayers and analytical areas in macular scans by spectral-domain OCT on the diagnostic ability of early glaucoma.

PubMed

Nakatani, Yusuke; Higashide, Tomomi; Ohkubo, Shinji; Sugiyama, Kazuhisa

2014-10-23

We investigated the influences of the inner retinal sublayers and analytical areas in macular scans by spectral-domain optical coherence tomography (OCT) on the diagnostic ability of early glaucoma. A total of 64 early (including 24 preperimetric) glaucomatous and 40 normal eyes underwent macular and peripapillary retinal nerve fiber layer (pRNFL) scans (3D-OCT-2000). The area under the receiver operating characteristics (AUC) for glaucoma diagnosis was determined from the average thickness of the total 100 grids (6 × 6 mm), central 44 grids (3.6 × 4.8 mm), and peripheral 56 grids (outside of the 44 grids), and for each macular sublayer: macular RNFL (mRNFL), ganglion cell layer plus inner plexiform layer (GCL/IPL), and mRNFL plus GCL/IPL (ganglion cell complex [GCC]). Correlation of OCT parameters with visual field parameters was evaluated by Spearman's rank correlation coefficients (rs). The GCC-related parameters had a significantly larger AUC (0.82-0.97) than GCL/IPL (0.81-0.91), mRNFL-related parameters (0.72-0.94), or average pRNFL (0.88) in more than half of all comparisons. The central 44 grids had a significantly lower AUC than other analytical areas in GCC and mRNFL thickness. Conversely, the peripheral 56 grids had a significantly lower AUC than the 100 grids in GCL/IPL inferior thickness. Inferior thickness of GCC (rs, 0.45-0.49) and mRNFL (rs, 0.43-0.51) showed comparably high correlations with central visual field parameters to average pRNFL thickness (rs, 0.41, 0.47) even in the central 44 grids. The diagnostic ability of macular OCT parameters for early glaucoma differed by inner retinal sublayers and also by the analytical areas studied. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Fully Automated Segmentation of Fluid/Cyst Regions in Optical Coherence Tomography Images With Diabetic Macular Edema Using Neutrosophic Sets and Graph Algorithms.

PubMed

Rashno, Abdolreza; Koozekanani, Dara D; Drayna, Paul M; Nazari, Behzad; Sadri, Saeed; Rabbani, Hossein; Parhi, Keshab K

2018-05-01

This paper presents a fully automated algorithm to segment fluid-associated (fluid-filled) and cyst regions in optical coherence tomography (OCT) retina images of subjects with diabetic macular edema. The OCT image is segmented using a novel neutrosophic transformation and a graph-based shortest path method. In neutrosophic domain, an image is transformed into three sets: (true), (indeterminate) that represents noise, and (false). This paper makes four key contributions. First, a new method is introduced to compute the indeterminacy set , and a new -correction operation is introduced to compute the set in neutrosophic domain. Second, a graph shortest-path method is applied in neutrosophic domain to segment the inner limiting membrane and the retinal pigment epithelium as regions of interest (ROI) and outer plexiform layer and inner segment myeloid as middle layers using a novel definition of the edge weights . Third, a new cost function for cluster-based fluid/cyst segmentation in ROI is presented which also includes a novel approach in estimating the number of clusters in an automated manner. Fourth, the final fluid regions are achieved by ignoring very small regions and the regions between middle layers. The proposed method is evaluated using two publicly available datasets: Duke, Optima, and a third local dataset from the UMN clinic which is available online. The proposed algorithm outperforms the previously proposed Duke algorithm by 8% with respect to the dice coefficient and by 5% with respect to precision on the Duke dataset, while achieving about the same sensitivity. Also, the proposed algorithm outperforms a prior method for Optima dataset by 6%, 22%, and 23% with respect to the dice coefficient, sensitivity, and precision, respectively. Finally, the proposed algorithm also achieves sensitivity of 67.3%, 88.8%, and 76.7%, for the Duke, Optima, and the university of minnesota (UMN) datasets, respectively.

Macular Ganglion Cell and Retinal Nerve Fiber Layer Thickness in Children With Refractive Errors-An Optical Coherence Tomography Study.

PubMed

Goh, Jody P; Koh, Victor; Chan, Yiong Huak; Ngo, Cheryl

2017-07-01

To study the distribution of macular ganglion cell-inner plexiform layer (GC-IPL) thickness and peripapillary retinal nerve fiber layer (RNFL) thickness in children with refractive errors. Two hundred forty-three healthy eyes from 139 children with refractive error ranging from -10.00 to +5.00 D were recruited from the National University Hospital Eye Surgery outpatient clinic. After a comprehensive ocular examination, refraction, and axial length (AL) measurement (IOLMaster), macular GC-IPL and RNFL thickness values were obtained with a spectral domain Cirrus high definition optical coherence tomography system (Carl Zeiss Meditec Inc.). Only scans with signal strength of >6/10 were included. Correlation between variables was calculated using the Pearson correlation coefficient. A multivariate analysis using mixed models was done to adjust for confounders. The mean spherical equivalent refraction was -3.20±3.51 D and mean AL was 24.39±1.72 mm. Average, minimum, superior, and inferior GC-IPL were 82.59±6.29, 77.17±9.65, 83.68±6.96, and 81.64±6.70 μm, respectively. Average, superior, and inferior peripapillary RNFL were 99.00±11.45, 123.20±25.81, and 124.24±22.23 μm, respectively. Average, superior, and inferior GC-IPL were correlated with AL (β=-2.056, P-value 0.000; β=-2.383, P-value 0.000; β=-1.721, P-value 0.000), but minimum GC-IPL was not (β=-1.056, P-value 0.115). None of the RNFL parameters were correlated with AL. This study establishes normative macular GC-IPL and RNFL thickness in children with refractive errors. Our results suggest that high definition optical coherence tomography RNFL parameters and minimum GC-IPL are not affected by AL or myopia in children, and therefore warrants further evaluation in pediatric glaucoma patients.

Macular retinal and choroidal thickness in unilateral amblyopia using swept-source optical coherence tomography.

PubMed

Araki, Syunsuke; Miki, Atsushi; Goto, Katsutoshi; Yamashita, Tsutomu; Takizawa, Go; Haruishi, Kazuko; Ieki, Yoshiaki; Kiryu, Junichi; Yaoeda, Kiyoshi

2017-09-15

To investigate macular retinal and choroidal thickness in amblyopic eyes compared to that in fellow and normal eyes using swept-source optical coherence tomography (SS-OCT). This study examined 31 patients with hyperopic anisometropic amblyopia (6.9 ± 3.8 years, mean ± standard deviation), 15 patients with strabismic amblyopia without anisometropia (7.9 ± 4.2 years), and 24 age-matched controls (7.8 ± 3.3 years). Retinal and choroidal thickness was measured by 3D scans using SS-OCT. A 6-mm area around the fovea was automatically analyzed using the Early Treatment Diabetic Retinopathy Study map. The thickness from SS-OCT was corrected for magnification error using individual axial length, spherical refraction, cylinder refraction, and corneal radius. Retinal thickness was divided into the macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL+IPL), ganglion cell complex (GCC), and the inner limiting membrane to the retinal pigment epithelium (ILM-RPE) thickness. Retinal and choroidal thickness was compared among amblyopic, fellow, and normal eyes. In both amblyopia groups, there was no significant difference in the mRNFL, GCL+IPL, and GCC thicknesses among the amblyopic, fellow, and control eyes. In the anisometropic amblyopia group, choroidal thickness (subfovea, center 1 mm, nasal and inferior of the inner ring, nasal of the outer ring, and center 6 mm) of amblyopic eyes were significantly greater than that of fellow and normal eyes. In contrast, none of the choroidal thicknesses were significantly different among the investigated eyes in the strabismic amblyopia group. We found no significant difference in inner retinal thickness in patients with unilateral amblyopia. Although there were significant differences in choroidal thickness with hyperopic anisometropic amblyopia, there was no significant difference for the strabismic amblyopia. The discrepancy in choroidal thickness between the two types of amblyopia may be due to both differences in ocular size and underlying mechanism.

Hunting high and low: disentangling primordial and late-time non-Gaussianity with cosmic densities in spheres

NASA Astrophysics Data System (ADS)

Uhlemann, C.; Pajer, E.; Pichon, C.; Nishimichi, T.; Codis, S.; Bernardeau, F.

2018-03-01

Non-Gaussianities of dynamical origin are disentangled from primordial ones using the formalism of large deviation statistics with spherical collapse dynamics. This is achieved by relying on accurate analytical predictions for the one-point probability distribution function and the two-point clustering of spherically averaged cosmic densities (sphere bias). Sphere bias extends the idea of halo bias to intermediate density environments and voids as underdense regions. In the presence of primordial non-Gaussianity, sphere bias displays a strong scale dependence relevant for both high- and low-density regions, which is predicted analytically. The statistics of densities in spheres are built to model primordial non-Gaussianity via an initial skewness with a scale dependence that depends on the bispectrum of the underlying model. The analytical formulas with the measured non-linear dark matter variance as input are successfully tested against numerical simulations. For local non-Gaussianity with a range from fNL = -100 to +100, they are found to agree within 2 per cent or better for densities ρ ∈ [0.5, 3] in spheres of radius 15 Mpc h-1 down to z = 0.35. The validity of the large deviation statistics formalism is thereby established for all observationally relevant local-type departures from perfectly Gaussian initial conditions. The corresponding estimators for the amplitude of the non-linear variance σ8 and primordial skewness fNL are validated using a fiducial joint maximum likelihood experiment. The influence of observational effects and the prospects for a future detection of primordial non-Gaussianity from joint one- and two-point densities-in-spheres statistics are discussed.

BHDD: Primordial black hole binaries code

NASA Astrophysics Data System (ADS)

Kavanagh, Bradley J.; Gaggero, Daniele; Bertone, Gianfranco

2018-06-01

BHDD (BlackHolesDarkDress) simulates primordial black hole (PBH) binaries that are clothed in dark matter (DM) halos. The software uses N-body simulations and analytical estimates to follow the evolution of PBH binaries formed in the early Universe.

Optic coherence tomography shows inflammation and degeneration in major depressive disorder patients correlated with disease severity.

PubMed

Kalenderoglu, Aysun; Çelik, Mustafa; Sevgi-Karadag, Ayse; Egilmez, Oguzhan Bekir

2016-11-01

Previous research has consistently detected inflammation in the etiology of depression and neuroimaging studies have demonstrated gray matter abnormalities implying a neurodegenerative process in depression. The aim of this study was to compare ganglion cell layer (GCL), and inner plexiform layer (IPL) volumes and retinal nerve fiber layer (RNFL) thickness between first episode and recurrent major depressive disorder (MDD) patients and controls using optic coherence tomography (OCT) in order to detect findings supporting a degenerative process. Also choroid thicknesses of the same groups were compared to examine effects of inflammation on MDD. This study included 50 recurrent MDD patients, 50 first episode MDD patients and 50 controls. OCT measurements were performed by a spectral OCT device. GCL and IPL volumes and RNFL and choroid thicknesses were measured automatically by the device. GCL and IPL volumes were significantly smaller in recurrent depression patients than first episode patients and in all MDD patients than controls. Also there were significant negative correlations between their volumes and disease severity parameters such as Ham-D and CGI scores, and disease duration. RNFL thicknesses were also lower in recurrent MDD patients than first episode patients and all MDD patients than controls but statistical significance was achieved only for global RNFL and temporal superior RNFL. Mean choroid thickness was higher in MDD patients than controls and in first episode MDD patients than recurrent MDD patients. Cross-sectional design of our study limits conclusions about progressive degeneration during the course of MDD. Lack of a control neuroimaging method like magnetic resonance imaging makes it hard to draw firm conclusions from our results. OCT finding of decreased GCL and IPL volumes supports previous research suggesting degeneration in MDD. OCT may be an important tool to track neurodegeneration in patients with major depression. Considering RNFL to be the latest layer that will be affected during course of degeneration, GCL and IPL volumes appear to be better parameters to follow. In addition, choroid may be an important structure to detect acute attack period and to follow inflammatory process in MDD like in systemic inflammatory diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Loop corrections to primordial non-Gaussianity

NASA Astrophysics Data System (ADS)

Boran, Sibel; Kahya, E. O.

2018-02-01

We discuss quantum gravitational loop effects to observable quantities such as curvature power spectrum and primordial non-Gaussianity of cosmic microwave background (CMB) radiation. We first review the previously shown case where one gets a time dependence for zeta-zeta correlator due to loop corrections. Then we investigate the effect of loop corrections to primordial non-Gaussianity of CMB. We conclude that, even with a single scalar inflaton, one might get a huge value for non-Gaussianity which would exceed the observed value by at least 30 orders of magnitude. Finally we discuss the consequences of this result for scalar driven inflationary models.

Probing the primordial universe with gravitational waves detectors

NASA Astrophysics Data System (ADS)

Wang, Yu-Tong; Cai, Yong; Liu, Zhi-Guo; Piao, Yun-Song

2017-01-01

The spectrum of primordial gravitational waves (GWs), especially its tilt nT, carries significant information about the primordial universe. Combining recent aLIGO and Planck2015+BK14 data, we find that the current limit is nT=0.016+0.614-0.989 at 95% C.L. We also estimate the impacts of Einstein Telescope and LISA on constraining nT. Moreover, based on the effective field theory of cosmological perturbations, we make an attempt to confront some models of early universe scenarios, which produce blue-tilted GWs spectrum (nT>0), with the corresponding datasets.

Primordial Prevention of Cardiometabolic Risk in Childhood.

PubMed

Tanrikulu, Meryem A; Agirbasli, Mehmet; Berenson, Gerald

2017-01-01

Fetal life and childhood are important in the development of cardiometabolic risk and later clinical disease of atherosclerosis, hypertension and diabetes mellitus. Molecular and environmental conditions leading to cardiometabolic risk in early life bring us a challenge to develop effective prevention and intervention strategies to reduce cardiovascular (CV) risk in children and later disease. It is important that prevention strategies begin at an early age to reduce future CV morbidity and mortality. Pioneering work from longitudinal studies such as Bogalusa Heart Study (BHS), the Finnish Youth Study and other programs provide an awareness of the need for public and health services to begin primordial prevention. The impending CV risk beginning in childhood has a significant socioeconomic burden. Directions to achieve primordial prevention of cardiometabolic risk in children have been developed by prior longitudinal studies. Based on those studies that show risk factors in childhood as precursors of adult CV risk, implementation of primordial prevention will have effects at broad levels. Considering the epidemic of obesity, the high prevalence of hypertension and cardiometabolic risk, prevention early in life is valuable. Comprehensive health education, such as 'Health Ahead/Heart Smart', for all elementary school age children is one approach to begin primordial prevention and can be included in public education beginning in kindergarten along with the traditional education subject matter.

The future of primordial features with large-scale structure surveys

NASA Astrophysics Data System (ADS)

Chen, Xingang; Dvorkin, Cora; Huang, Zhiqi; Namjoo, Mohammad Hossein; Verde, Licia

2016-11-01

Primordial features are one of the most important extensions of the Standard Model of cosmology, providing a wealth of information on the primordial Universe, ranging from discrimination between inflation and alternative scenarios, new particle detection, to fine structures in the inflationary potential. We study the prospects of future large-scale structure (LSS) surveys on the detection and constraints of these features. We classify primordial feature models into several classes, and for each class we present a simple template of power spectrum that encodes the essential physics. We study how well the most ambitious LSS surveys proposed to date, including both spectroscopic and photometric surveys, will be able to improve the constraints with respect to the current Planck data. We find that these LSS surveys will significantly improve the experimental sensitivity on features signals that are oscillatory in scales, due to the 3D information. For a broad range of models, these surveys will be able to reduce the errors of the amplitudes of the features by a factor of 5 or more, including several interesting candidates identified in the recent Planck data. Therefore, LSS surveys offer an impressive opportunity for primordial feature discovery in the next decade or two. We also compare the advantages of both types of surveys.

The future of primordial features with large-scale structure surveys

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

Chen, Xingang; Namjoo, Mohammad Hossein; Dvorkin, Cora

2016-11-01

Primordial features are one of the most important extensions of the Standard Model of cosmology, providing a wealth of information on the primordial Universe, ranging from discrimination between inflation and alternative scenarios, new particle detection, to fine structures in the inflationary potential. We study the prospects of future large-scale structure (LSS) surveys on the detection and constraints of these features. We classify primordial feature models into several classes, and for each class we present a simple template of power spectrum that encodes the essential physics. We study how well the most ambitious LSS surveys proposed to date, including both spectroscopicmore » and photometric surveys, will be able to improve the constraints with respect to the current Planck data. We find that these LSS surveys will significantly improve the experimental sensitivity on features signals that are oscillatory in scales, due to the 3D information. For a broad range of models, these surveys will be able to reduce the errors of the amplitudes of the features by a factor of 5 or more, including several interesting candidates identified in the recent Planck data. Therefore, LSS surveys offer an impressive opportunity for primordial feature discovery in the next decade or two. We also compare the advantages of both types of surveys.« less

Gravitational wave production by Hawking radiation from rotating primordial black holes

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

Dong, Ruifeng; Kinney, William H.; Stojkovic, Dejan, E-mail: ruifengd@buffalo.edu, E-mail: whkinney@buffalo.edu, E-mail: ds77@buffalo.edu

In this paper we analyze in detail a rarely discussed question of gravity wave production from evaporating primordial black holes. These black holes emit gravitons which are, at classical level, registered as gravity waves. We use the latest constraints on their abundance, and calculate the power emitted in gravitons at the time of their evaporation. We then solve the coupled system of equations that gives us the evolution of the frequency and amplitude of gravity waves during the expansion of the universe. The spectrum of gravitational waves that can be detected today depends on multiple factors: fraction of the totalmore » energy density which was occupied by primordial black holes, the epoch in which they were formed, and quantities like their mass and angular momentum. We conclude that very small primordial black holes which evaporate before the big-bang nucleosynthesis emit gravitons whose spectral energy fraction today can be as large as 10{sup −7.5}. On the other hand, those which are massive enough so that they still exist now can yield a signal as high as 10{sup −6.5}. However, typical frequencies of the gravity waves from primordial black holes are still too high to be observed with the current and near future gravity wave observations.« less

Probing the cosmological initial conditions using the CMB

NASA Astrophysics Data System (ADS)

Yadav, Amit P. S.

In the last few decades, advances in observational cosmology have given us a standard model of cosmology. The basic cosmological parameters have been laid out to high precision. Cosmologists have started asking questions about the nature of the cosmological initial conditions. Many ambitious experiments such as Planck satellite, EBEX, ACT, CAPMAP, QUaD, BICEP, SPIDER, QUIET, and GEM are underway. Experiments like these will provide us with a wealth of information about CMB polarization, CMB lensing, and polarization foregrounds. These experiments will be complemented with great observational campaigns to map the 3D structure in the Universe and new particle physics constraints from the Large Hadron Collider. In my graduate work I have made explicit how observations of the CMB temperature and E-polarization anisotropies can be combined to provide optimal constraints on models of the early universe at the highest energies. I have developed new ways of constraining models of the early universe using CMB temperature and polarization data. Inflation is one of the most promising theories of the early universe. Different inflationary models predict different amounts of non-Gaussian perturbations. Although any non-Gaussianity predicted by the canonical inflation model is very small, there exist models which can generate significant amounts of non-Gaussianities. Hence any characterization of non-Gaussianity of the primordial perturbations constrains the models of inflation. The information in the bispectrum (or higher order moments) is completely independent of the power spectrum constraints on the amplitude of primordial power spectrum (A), the scalar spectral index of the primordial power spectrum ns, and the running of the primordial power spectrum. My work has made it possible to extract the bispectrum information from large, high resolution CMB temperature and polarization data. We have demonstrated that the primordial adiabatic perturbations can be reconstructed using CMB temperature and E-polarization information (Yadav and Wandelt 2005). One of the main motivations of reconstructing the primordial perturbations is to study the primordial non-Gaussianities. Since the amplitude of primordial non-Gaussianity is very small, any enhancement in sensitivity to the primordial features is useful because it improves the characterization of the primordial non-Gaussianity. Our reconstruction allows us to be more sensitive to the primordial features, whereas most of the current probes of non-Gaussianity do not specifically select for them. We have also developed a fast cubic (bispectrum) estimator of non-Gaussianity f NL of local type, using combined temperature and E-polarization data (Yadavet al. 2007). The estimator is computationally efficient, scaling as O( N 3/2 ) compared to the O( N 5/2 ) scaling of the brute force bispectrum calculation for sky maps with N pixels. For the Planck satellite, this translates into a speed-up by factors of millions, reducing the required computing time from thousands of years to just hours and thus making f NL estimation feasible. The speed of our estimator allows us to study its statistical properties using Monte Carlo simulations. Our estimator in its original form was optimal for homogeneous noise. In order to apply our estimator to realistic data, the estimator needed to be able to deal with inhomogeneous noise. We have generalized the fast polarized estimator to deal with inhomogeneous noise. The generalized estimator is also computationally efficient, scaling as O( N 3/2 ). Furthermore, we have studied and characterized our estimators in the presence of realistic noise, finite resolution, incomplete sky-coverage, and using non-Gaussian CMB maps (Yadavet al. 2008a). We have also developed a numerical code to generate CMB temperature and polarization non-Gaussian maps starting from a given primordial non-Gaussianity (f NL ) (Liguori et al. 2007). In the process of non-Gaussian CMB map making, the code also generates corresponding non-Gaussian primordial curvature perturbations. We use these curvature perturbations to quantify the quality of the tomographic reconstruction method described in (Yadav and Wandelt 2005). We check whether the tomographic reconstruction method preserves the non-Gaussian features, especially the phase information, in the reconstructed curvature perturbations (Yadav et al. in preparation). Finally, using our estimator we found (Yadav and Wandelt 2008) evidence for primordial non-Gaussianity of the local type (f NL ) in the temperature anisotropy of the Cosmic Microwave Background. Analyzing the bispectrum of the WMAP 3-year data up to l max =750 we find 27< f NL <147 (95% CL). This amounts to a rejection of f NL =0 at 2.8s, disfavoring canonical single field slow-roll inflation. The signal is robust to variations in l max , frequency, and masks. No known foreground, instrument systematic, or secondary anisotropy explains it. We explore the impact of several analysis choices on the quoted significance and find 2.5s to be conservative.

The morphology and classification of α ganglion cells in the rat retinae: a fractal analysis study.

PubMed

Jelinek, Herbert F; Ristanović, Dušan; Milošević, Nebojša T

2011-09-30

Rat retinal ganglion cells have been proposed to consist of a varying number of subtypes. Dendritic morphology is an essential aspect of classification and a necessary step toward understanding structure-function relationships of retinal ganglion cells. This study aimed at using a heuristic classification procedure in combination with the box-counting analysis to classify the alpha ganglion cells in the rat retinae based on the dendritic branching pattern and to investigate morphological changes with retinal eccentricity. The cells could be divided into two groups: cells with simple dendritic pattern (box dimension lower than 1.390) and cells with complex dendritic pattern (box dimension higher than 1.390) according to their dendritic branching pattern complexity. Both were further divided into two subtypes due to the stratification within the inner plexiform layer. In the present study we have shown that the alpha rat RCGs can be classified further by their dendritic branching complexity and thus extend those of previous reports that fractal analysis can be successfully used in neuronal classification, particularly that the fractal dimension represents a robust and sensitive tool for the classification of retinal ganglion cells. A hypothesis of possible functional significance of our classification scheme is also discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Diversity and wiring variability of visual local neurons in the Drosophila medulla M6 stratum.

PubMed

Chin, An-Lun; Lin, Chih-Yung; Fu, Tsai-Feng; Dickson, Barry J; Chiang, Ann-Shyn

2014-12-01

Local neurons in the vertebrate retina are instrumental in transforming visual inputs to extract contrast, motion, and color information and in shaping bipolar-to-ganglion cell transmission to the brain. In Drosophila, UV vision is represented by R7 inner photoreceptor neurons that project to the medulla M6 stratum, with relatively little known of this downstream substrate. Here, using R7 terminals as references, we generated a 3D volume model of the M6 stratum, which revealed a retinotopic map for UV representations. Using this volume model as a common 3D framework, we compiled and analyzed the spatial distributions of more than 200 single M6-specific local neurons (M6-LNs). Based on the segregation of putative dendrites and axons, these local neurons were classified into two families, directional and nondirectional. Neurotransmitter immunostaining suggested a signal routing model in which some visual information is relayed by directional M6-LNs from the anterior to the posterior M6 and all visual information is inhibited by a diverse population of nondirectional M6-LNs covering the entire M6 stratum. Our findings suggest that the Drosophila medulla M6 stratum contains diverse LNs that form repeating functional modules similar to those found in the vertebrate inner plexiform layer. © 2014 Wiley Periodicals, Inc.

Morphology of retinal ganglion cells in the ferret (Mustela putorius furo).

PubMed

Isayama, Tomoki; O'Brien, Brendan J; Ugalde, Irma; Muller, Jay F; Frenz, Aaron; Aurora, Vikas; Tsiaras, William; Berson, David M

2009-12-01

The ferret is the premiere mammalian model of retinal and visual system development, but the spectrum and properties of its retinal ganglion cells are less well understood than in another member of the Carnivora, the domestic cat. Here, we have extensively surveyed the dendritic architecture of ferret ganglion cells and report that the classification scheme previously developed for cat ganglion cells can be applied with few modifications to the ferret retina. We confirm the presence of alpha and beta cells in ferret retina, which are very similar to those in cat retina. Both cell types exhibited an increase in dendritic field size with distance from the area centralis (eccentricity) and with distance from the visual streak. Both alpha and beta cell populations existed as two subtypes whose dendrites stratified mainly in sublamina a or b of the inner plexiform layer. Six additional morphological types of ganglion cells were identified: four monostratified cell types (delta, epsilon, zeta, and eta) and two bistratified types (theta and iota). These types closely resembled their counterparts in the cat in terms of form, relative field size, and stratification. Our data indicate that, among carnivore species, the retinal ganglion cells resemble one another closely and that the ferret is a useful model for studies of the ontogenetic differentiation of ganglion cell types.

Short-wavelength cone-opponent retinal ganglion cells in mammals.

PubMed

Marshak, David W; Mills, Stephen L

2014-03-01

In all of the mammalian species studied to date, the short-wavelength-sensitive (S) cones and the S-cone bipolar cells that receive their input are very similar, but the retinal ganglion cells that receive synapses from the S-cone bipolar cells appear to be quite different. Here, we review the literature on mammalian retinal ganglion cells that respond selectively to stimulation of S-cones and respond with opposite polarity to longer wavelength stimuli. There are at least three basic mechanisms to generate these color-opponent responses, including: (1) opponency is generated in the outer plexiform layer by horizontal cells and is conveyed to the ganglion cells via S-cone bipolar cells, (2) inputs from bipolar cells with different cone inputs and opposite response polarity converge directly on the ganglion cells, and (3) inputs from S-cone bipolar cells are inverted by S-cone amacrine cells. These are not mutually exclusive; some mammalian ganglion cells that respond selectively to S-cone stimulation seem to utilize at least two of them. Based on these findings, we suggest that the small bistratified ganglion cells described in primates are not the ancestral type, as proposed previously. Instead, the known types of ganglion cells in this pathway evolved from monostratified ancestral types and became bistratified in some mammalian lineages.

Distribution of protein kinase C isoforms in the cat retina.

PubMed

Fyk-Kolodziej, Bozena; Cai, Wenhui; Pourcho, Roberta G

2002-01-01

Immunocytochemical localization was carried out for five isoforms of protein kinase C (PKC) in the cat retina. In common with other mammalian species, PKCalpha was found in rod bipolar cells. Staining was also seen in a small population of cone bipolar cells with axon terminals ramifying near the middle of the inner plexiform layer (IPL). PKCbetaI was localized to rod bipolar cells, one class of cone bipolar cell, and numerous amacrine and displaced amacrine cells. Staining for PKCbetaI was seen in three types of cone bipolar cells as well as in amacrine and ganglion cells. Immunoreactivity for both PKCepsilon and PKCzeta was found in rod bipolar cells; PKCepsilon was also seen in a population of cone bipolar cells and a few amacrine and ganglion cells whereas PKCzeta was found in all ganglion cells. Double-label immunofluorescence studies showed that dendrites of the two PKCbetaII-positive OFF-cone bipolar cells exhibit immmunoreactivity for the kainate-selective glutamate receptor GluR5. The third PKCbetaII cone bipolar is an ON-type cell and did not stain for GluR5. The retinal distribution of these isoforms of PKC is consistent with a role in modulation of various aspects of neurotransmission including synaptic vesicle release and regulation of receptor molecules.

THE SECOND BLIND SPOT: SMALL RETINAL VESSEL VASCULOPATHY AFTER VACCINATION AGAINST NEISSERIA MENINGITIDIS AND YELLOW FEVER.

PubMed

Moysidis, Stavros N; Koulisis, Nicole; Patel, Vivek R; Kashani, Amir H; Rao, Narsing A; Humayun, Mark S; Rodger, Damien C

2017-01-01

To describe a case of small retinal vessel vasculopathy postvaccination. We report the case of a 41-year-old white man who presented with a "second blind spot," describing a nasal scotoma in the right eye that started 4 days after vaccinations against Neisseria meningitidis and the yellow fever virus, and after a 2-month period of high stress and decreased sleep. Clinical examination, Humphrey visual field testing, and multimodal imaging with fundus photographs, autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography and angiography were performed. Clinical examination revealed a well-circumscribed, triangular area of retinal graying of about 1-disk diameter in size, located at the border of the temporal macula. This corresponded to a deep scotoma similar in size to the physiologic blind spot on Humphrey visual field 24-2 testing. There was mild hypoautofluoresence of this lesion on autofluorescence, hypofluorescence on fluorescein angiography, and focal attenuation of a small artery just distal to the bifurcation of an artery supplying the involved area. Spectral domain optical coherence tomography through the lesion conveyed hyperreflectivity most prominent in the inner and outer plexiform layers, with extension of the hyperreflectivity into the ganglion cell and inner nuclear layers. Spectral domain optical coherence tomography angiography demonstrated arteriolar and capillary dropout, more pronounced in the superficial retinal layer compared to the deeper retinal layer. At 1-month follow-up, his scotoma improved with monitoring, with reduction from -32 dB to -7 dB on Humphrey visual field testing. There was clinical resolution of the area of graying and decreased hyperreflectivity on spectral domain optical coherence tomography, with atrophy of the inner retina. Spectral domain optical coherence tomography angiography showed progression of arteriolar and capillary dropout, more so in the superficial than in the deep capillary plexus. We describe a case of small artery occlusion in a previously healthy patient, 4 days after vaccination against N. meningitidis and yellow fever. Fluorescein angiography yielded greater diagnostic value than OCTA for evaluating the occlusion, whereas spectral domain optical coherence tomography angiography enabled better visualization of capillary dropout and layer-specific assessment. Further research is required to determine whether vaccination in general, or directed specifically at N. meningitidis or yellow fever, is associated with small vessel vasculopathy and the underlying pathogenesis.

Short-term culture of adult bovine ovarian tissues: chorioallantoic membrane (CAM) vs. traditional in vitro culture systems.

PubMed

Beck, Kylie; Singh, Jaswant; Dar, Mohammad Arshud; Anzar, Muhammad

2018-03-09

A suitable culture system is important for follicle growth in adult bovine ovarian tissue. This study aimed to assess the avian chorioallantoic membrane (CAM) for short-term culture of adult bovine ovarian tissues compared with a traditional in vitro culture system. Ovarian cortical tissues (1-2 mm 3 ), collected from slaughtered adult cows, were randomly assigned to control, CAM or in vitro culture groups. In the control group, ovarian tissues were fixed with paraformaldehyde without culture. In CAM and in vitro culture groups, the ovarian tissues were cultured for up to 5 days and then fixed. Ovarian tissues were examined on culture days 0, 1, 3 and 5 for angiogenesis, follicle morphology and growth. In all groups, primordial and growing (healthy and atretic) follicle densities were determined. In the CAM culture, the avian blood vessel density increased (p < 0.01) over time with a decline (p < 0.001) in the bovine blood vessel density. Healthy primordial, atretic primordial and healthy growing follicle densities were higher (p < 0.05) in CAM-cultured ovarian tissues than in vitro-cultured tissues. Regardless of the culture system, the density of healthy primordial follicles decreased (p < 0.001) over time with an increase in healthy growing follicles on day 3 (p < 0.01) and an increase in atretic (primordial and growing) follicles during the 5-day culture period (p < 0.001). The proportions of healthy primordial and atretic growing follicles were also affected by culture day (p < 0.001). The CAM culture in chick embryos supported the bovine ovarian tissue grafts for 3 days demonstrating that CAM can be used as a satisfactory short-term culture system to assess ovarian tissue health, and to study follicle activation and development.

Synergistic effect of melatonin and ghrelin in preventing cisplatin-induced ovarian damage via regulation of FOXO3a phosphorylation and binding to the p27Kip1 promoter in primordial follicles.

PubMed

Jang, Hoon; Na, Younghwa; Hong, Kwonho; Lee, Sangho; Moon, Sohyeon; Cho, Minha; Park, Miseon; Lee, Ok-Hee; Chang, Eun Mi; Lee, Dong Ryul; Ko, Jung Jae; Lee, Woo Sik; Choi, Youngsok

2017-10-01

Premature ovarian failure during chemotherapy is a serious problem for young women with cancer. To preserve the fertility of these patients, approaches to prevent chemotherapy-induced ovarian failure are needed. In a previous study, we reported that melatonin treatment prevents the depletion of the dormant follicle pool via repression of the simultaneous activation of dormant primordial follicles by cisplatin. However, melatonin's protective effect was only partial and thus insufficient. In this study, we found that the hormone ghrelin enhances the protective effect of melatonin against cisplatin-induced ovarian failure in mouse model. Co-administration of melatonin and ghrelin more effectively prevented cisplatin-induced follicle disruption. Simultaneous treatment with melatonin and ghrelin almost restored the number of primordial follicles and the corpus luteum in cisplatin-treated ovaries, compared with single administration. We found melatonin and ghrelin receptors on the cell membrane of premature oocytes of primordial follicles. In addition, melatonin and ghrelin co-administration inhibited the cisplatin-induced phosphorylation of PTEN and FOXO3a that induces cytoplasmic translocation of FOXO3a. Inhibition of FOXO3a phosphorylation by melatonin and ghrelin increased the binding affinity of FOXO3a for the p27 Kip1 promoter in primordial follicles. Co-administration of melatonin and ghrelin in cisplatin-treated ovaries restored the expression of p27 Kip1 , which is critical for retention of the dormant status of primordial follicles. In conclusion, these findings suggest that melatonin and ghrelin co-administration is suitable for use as a fertoprotective adjuvant therapy during cisplatin chemotherapy in young female cancer patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detectability of primordial gravitational waves produced in bouncing models

NASA Astrophysics Data System (ADS)

Pinto-Neto, Nelson; Scardua, Arthur

2017-06-01

It is widely known that bouncing models with a dust hydrodynamical fluid satisfying cs2=pd/ρd≈0 , where cs , pd , ρd are the sound velocity, pressure, and energy density of the dust fluid, respectively, have almost scale invariant spectrum of scalar perturbations and negligible primordial gravitational waves. We investigate whether adding another fluid with 1 /3

POLARBEAR constraints on cosmic birefringence and primordial magnetic fields

DOE PAGES

Ade, Peter A. R.; Arnold, Kam; Atlas, Matt; ...

2015-12-08

Here, we constrain anisotropic cosmic birefringence using four-point correlations of even-parity E-mode and odd-parity B-mode polarization in the cosmic microwave background measurements made by the POLARization of the Background Radiation (POLARBEAR) experiment in its first season of observations. We find that the anisotropic cosmic birefringence signal from any parity-violating processes is consistent with zero. The Faraday rotation from anisotropic cosmic birefringence can be compared with the equivalent quantity generated by primordial magnetic fields if they existed. The POLARBEAR nondetection translates into a 95% confidence level (C.L.) upper limit of 93 nanogauss (nG) on the amplitude of an equivalent primordial magneticmore » field inclusive of systematic uncertainties. This four-point correlation constraint on Faraday rotation is about 15 times tighter than the upper limit of 1380 nG inferred from constraining the contribution of Faraday rotation to two-point correlations of B-modes measured by Planck in 2015. Metric perturbations sourced by primordial magnetic fields would also contribute to the B-mode power spectrum. Using the POLARBEAR measurements of the B-mode power spectrum (two-point correlation), we set a 95% C.L. upper limit of 3.9 nG on primordial magnetic fields assuming a flat prior on the field amplitude. This limit is comparable to what was found in the Planck 2015 two-point correlation analysis with both temperature and polarization. Finally, we perform a set of systematic error tests and find no evidence for contamination. This work marks the first time that anisotropic cosmic birefringence or primordial magnetic fields have been constrained from the ground at subdegree scales.« less

Primordial Black Holes from First Principles (Overview)

NASA Astrophysics Data System (ADS)

Lam, Casey; Bloomfield, Jolyon; Moss, Zander; Russell, Megan; Face, Stephen; Guth, Alan

2017-01-01

Given a power spectrum from inflation, our goal is to calculate, from first principles, the number density and mass spectrum of primordial black holes that form in the early universe. Previously, these have been calculated using the Press- Schechter formalism and some demonstrably dubious rules of thumb regarding predictions of black hole collapse. Instead, we use Monte Carlo integration methods to sample field configurations from a power spectrum combined with numerical relativity simulations to obtain a more accurate picture of primordial black hole formation. We demonstrate how this can be applied for both Gaussian perturbations and the more interesting (for primordial black holes) theory of hybrid inflation. One of the tools that we employ is a variant of the BBKS formalism for computing the statistics of density peaks in the early universe. We discuss the issue of overcounting due to subpeaks that can arise from this approach (the ``cloud-in-cloud'' problem). MIT UROP Office- Paul E. Gray (1954) Endowed Fund.

Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: Clinical homogeneity but also unreported malformations.

PubMed

Barraza-García, Jimena; Iván Rivera-Pedroza, Carlos; Salamanca, Luis; Belinchón, Alberta; López-González, Vanesa; Sentchordi-Montané, Lucía; del Pozo, Ángela; Santos-Simarro, Fernando; Campos-Barros, Ángel; Lapunzina, Pablo; Guillén-Navarro, Encarna; González-Casado, Isabel; García-Miñaur, Sixto; Heath, Karen E

2016-01-01

Primordial dwarfism encompasses rare conditions characterized by severe intrauterine growth retardation and growth deficiency throughout life. Recently, three POC1A mutations have been reported in six families with the primordial dwarfism, SOFT syndrome (Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis). Using a custom-designed Next-generation sequencing skeletal dysplasia panel, we have identified two novel homozygous POC1A mutations in two individuals with primordial dwarfism. The severe growth retardation and the facial profiles are strikingly similar between our patients and those described previously. However, one of our patients was diagnosed with severe foramen magnum stenosis and subglottic tracheal stenosis, malformations not previously associated with this syndrome. Our findings confirm that POC1A mutations cause SOFT syndrome and that mutations in this gene should be considered in patients with severe pre- and postnatal short stature, symmetric shortening of long bones, triangular facies, sparse hair and short, thickened distal phalanges. © 2015 Wiley Periodicals, Inc.

Recurrence of 49-base decamers, nonomers, and octamers within mouse C mu gene of Ig heavy chain and its primordial building block.

PubMed Central

Yazaki, A; Ohno, S

1983-01-01

Within the published 2,168-base-long mouse C mu gene of Ig heavy chain consisting of four coding and four noncoding segments, 2 base decamers, 8 nonomers, and 39 octamers recurred. Recurring base heptamers (about 100) and hexamers (about 350) were simply too numerous to merit individual identification. In spite of extensive overlaps between these recurring base decamers to hexamers, they occupied nearly the entire length of mouse Ig C mu gene. As with other genes of the beta-sheet-forming beta 2-microglobulin family, the Ig C mu gene (flanking and intervening noncoding sequences included) is not a unique sequence but rather it is degenerate repeats of the 45-base-long primordial building-block sequence uniquely its own. This primordial building block must originally have specified the 15-amino-acid-residue-long primordial arm of beta-sheet-forming loops, the characteristics of the beta 2-microglobulin family of polypeptides. PMID:6403948

THM and primordial nucleosynthesis: Results and perspectives

NASA Astrophysics Data System (ADS)

Pizzone, R. G.; Spartá, R.; Bertulani, C.; Spitaleri, C.; La Cognata, M.; Lamia, L.; Tumino, A.

2017-09-01

Big Bang Nucleosynthesis (BBN) requires several nuclear physics inputs and nuclear reaction rates. An up-to-date compilation of direct cross sections of d(d,p)t, d(d,n) 3 He and 3 He(d,p) 4 He reactions is given, being these ones among the most uncertain bare-nucleus cross sections. An intense experimental effort has been carried on in the last decade to apply the Trojan Horse Method (THM) to study reactions of relevance for the BBN and measure their astrophysical S( E) -factor. The reaction rates and the relative error for the four reactions of interest are then numerically calculated in the temperature ranges of relevance for BBN ( 0.01

Spins of primordial black holes formed in the matter-dominated phase of the Universe

NASA Astrophysics Data System (ADS)

Harada, Tomohiro; Yoo, Chul-Moon; Kohri, Kazunori; Nakao, Ken-Ichi

2017-10-01

Angular momentum plays very important roles in the formation of primordial black holes in the matter-dominated phase of the Universe if it lasts sufficiently long. In fact, most collapsing masses are bounced back due to centrifugal force, since angular momentum significantly grows before collapse. For masses with q ≤qc≃2.4 I1 /3σH1 /3 , where q is a nondimensional initial quadrupole moment parameter, σH is the density fluctuation at horizon entry t =tH, and I is a parameter of the order of unity, angular momentum gives a suppression factor ˜exp (-0.15 I4 /3σH-2 /3) to the production rate. As for masses with q >qc, the suppression factor is even stronger as ˜exp (-0.0046 q4/σH2) . We derive the spin distribution of primordial black holes and find that most of the primordial black holes are rapidly rotating near the extreme value a*=1 , where a* is the nondimensional Kerr parameter at their formation. The smaller σH is, the stronger the tendency towards the extreme rotation. Combining this result with the effect of anisotropy, we numerically and semianalytically estimate the production rate β0 of primordial black holes. Then we find that β0≃1.9 ×10-6fq(qc)I6σH2exp (-0.15 I4 /3σH-2 /3) for σH≲0.005 , while β0≃0.05556 σH5 for 0.005 ≲σH≲0.2 , where fq(qc) is the fraction of masses whose q is smaller than qc and we assume fq(qc) is not too small. We argue that matter domination significantly enhances the production of primordial black holes despite the suppression factor. If the end time tend of the matter-dominated phase satisfies tend≲(0.4 I σH)-1tH, the effect of the finite duration significantly suppresses primordial black hole formation and weakens the tendency towards large spins.

Subunit- and pathway-specific localization of NMDA receptors and scaffolding proteins at ganglion cell synapses in rat retina

PubMed Central

Zhang, Jun; Diamond, Jeffrey S.

2014-01-01

Retinal ganglion cells (RGCs) receive excitatory glutamatergic input from ON and OFF bipolar cells in distinct sublaminae of the inner plexiform layer (IPL). AMPA and NMDA receptors (AMPARs and NMDARs) mediate excitatory inputs in both synaptic layers, but specific roles for NMDARs at RGC synapses remain unclear. NMDARs comprise NR1 and NR2 subunits and are anchored by membrane associated guanylate kinases (MAGUKs), but it is unknown whether particular NR2 subunits associate preferentially with particular NR1 splice variants and MAGUKs. Here, we used postembedding immunogold electron microscopy (EM) techniques to examine the subsynaptic localization of NMDAR subunits and MAGUKs at ON and OFF synapses onto rat RGCs. We found that the NR2A subunit, the NR1C2‘ splice variant and MAGUKs PSD-95 and PSD-93 are localized to the postsynaptic density (PSD), preferentially at OFF synapses, whereas the NR2B subunit, the NR1C2 splice variant and the MAGUK SAP102 are localized perisynaptically, with NR2B exhibiting a preference for ON synapses. Consistent with these anatomical data, spontaneous EPSCs (sEPSCs) recorded from OFF cells exhibited an NMDAR component that was insensitive to the NR2B antagonist Ro 25-6981. In ON cells, sEPSCs expressed an NMDAR component, partially sensitive to Ro 25-6981, only when glutamate transport was inhibited, indicating perisynaptic expression of NR2B NMDARs. These results provide the first evidence for preferential association of particular NR1 splice variants, NR2 subunits and MAGUKs at central synapses and suggest that different NMDAR subtypes may play specific roles at functionally distinct synapses in the retinal circuitry. PMID:19339621

Asymmetric Macular Structural Damage Is Associated With Relative Afferent Pupillary Defects in Patients With Glaucoma

PubMed Central

Gracitelli, Carolina P. B.; Tatham, Andrew J.; Zangwill, Linda M.; Weinreb, Robert N.; Abe, Ricardo Y.; Diniz-Filho, Alberto; Paranhos, Augusto; Baig, Saif; Medeiros, Felipe A.

2016-01-01

Purpose We examined the relationship between relative afferent pupillary defects (RAPDs) and macular structural damage measured by macular thickness and macular ganglion cell-inner plexiform layer (mGCIPL) thickness in patients with glaucoma. Methods A cross-sectional study was done of 106 glaucoma patients and 85 healthy individuals from the Diagnostic Innovations in Glaucoma Study. All subjects underwent standard automated perimetry (SAP) and optic nerve and macular imaging using Cirrus Spectral Domain Optical Coherence Tomography (SDOCT). Glaucoma was defined as repeatable abnormal SAP or progressive glaucomatous changes on stereo photographs. Pupil responses were assessed using an automated pupillometer, which records the magnitude of RAPD (RAPD score), with additional RAPD scores recorded for each of a series of colored stimuli (blue, red, green, and yellow). The relationship between RAPD score and intereye differences (right minus left eye) in circumpapillary retinal nerve fiber layer (cpRNFL) thickness, mGCIPL, macular thickness, and SAP mean deviation (MD), was examined using linear regression. Results There was fair correlation between RAPD score and asymmetric macular structural damage measured by intereye difference in mGCIPL thickness (R2 = 0.285, P < 0.001). The relationship between RAPD score and intereye difference in macular thickness was weaker (R2 = 0.167, P < 0.001). Intereye difference in cpRNFL thickness (R2 = 0.350, P < 0.001) and SAP MD (R2 = 0.594, P < 0.001) had stronger association with RAPD scores compared to intereye difference in mGCIPL and macular thickness. Conclusions Objective assessment of pupillary responses using a pupillometer was associated with asymmetric macular structural damage in patients with glaucoma. PMID:27064394

Diabetic retinal pigment epitheliopathy: fundus autofluorescence and spectral-domain optical coherence tomography findings.

PubMed

Kang, Eui Chun; Seo, Yuri; Byeon, Suk Ho

2016-10-01

To describe the characteristics of an unfamiliar disease entity, diabetic retinal pigment epitheliopathy (DRPE), using fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT). This retrospective study included 17 eyes from 10 proliferative diabetic retinopathy (PDR) patients with granular hypo-autofluorescence and/or variable hyper-autofluorescence on FAF (DRPE group) and 17 eyes from 10 age- and sex-matched PDR patients without abnormal autofluorescence (PDR group). Eyes with diabetic macular edema were excluded. Visual acuity (VA), retinal thickness (RT), and choroidal thickness (CT) were compared between the groups. Eyes in the DRPE group had worse logMAR VA than eyes in the PDR group (0.369 ± 0.266 vs. 0.185 ± 0.119; P = 0.026). The thickness of the retinal pigment epithelium plus the inner segment/outer segment of the photoreceptors was reduced to a greater degree in the DRPE group than the PDR group (P < 0.001). Moreover, the thickness of the outer nuclear layer plus the outer plexiform layer was thinner in the DRPE group than in the PDR (P = 0.013). However, the thickness of the inner retina showed no differences between the two groups. CT was significantly thicker in the DRPE group than in the PDR group (329.00 ± 33.76 vs. 225.62 ± 37.47 μm; P < 0.001). Eyes with DRPE showed reduced VA, a thinner outer retina, and thicker choroid in comparison with eyes with PDR. Alterations of autofluorescence on FAF and changes in the outer retinal thickness and CT on SD-OCT can be helpful for differentiating DRPE in patients with PDR.

A Diagnostic Calculator for Detecting Glaucoma on the Basis of Retinal Nerve Fiber Layer, Optic Disc, and Retinal Ganglion Cell Analysis by Optical Coherence Tomography.

PubMed

Larrosa, José Manuel; Moreno-Montañés, Javier; Martinez-de-la-Casa, José María; Polo, Vicente; Velázquez-Villoria, Álvaro; Berrozpe, Clara; García-Granero, Marta

2015-10-01

The purpose of this study was to develop and validate a multivariate predictive model to detect glaucoma by using a combination of retinal nerve fiber layer (RNFL), retinal ganglion cell-inner plexiform (GCIPL), and optic disc parameters measured using spectral-domain optical coherence tomography (OCT). Five hundred eyes from 500 participants and 187 eyes of another 187 participants were included in the study and validation groups, respectively. Patients with glaucoma were classified in five groups based on visual field damage. Sensitivity and specificity of all glaucoma OCT parameters were analyzed. Receiver operating characteristic curves (ROC) and areas under the ROC (AUC) were compared. Three predictive multivariate models (quantitative, qualitative, and combined) that used a combination of the best OCT parameters were constructed. A diagnostic calculator was created using the combined multivariate model. The best AUC parameters were: inferior RNFL, average RNFL, vertical cup/disc ratio, minimal GCIPL, and inferior-temporal GCIPL. Comparisons among the parameters did not show that the GCIPL parameters were better than those of the RNFL in early and advanced glaucoma. The highest AUC was in the combined predictive model (0.937; 95% confidence interval, 0.911-0.957) and was significantly (P = 0.0001) higher than the other isolated parameters considered in early and advanced glaucoma. The validation group displayed similar results to those of the study group. Best GCIPL, RNFL, and optic disc parameters showed a similar ability to detect glaucoma. The combined predictive formula improved the glaucoma detection compared to the best isolated parameters evaluated. The diagnostic calculator obtained good classification from participants in both the study and validation groups.

Improving Glaucoma Detection Using Spatially Correspondent Clusters of Damage and by Combining Standard Automated Perimetry and Optical Coherence Tomography

PubMed Central

Raza, Ali S.; Zhang, Xian; De Moraes, Carlos G. V.; Reisman, Charles A.; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

2014-01-01

Purpose. To improve the detection of glaucoma, techniques for assessing local patterns of damage and for combining structure and function were developed. Methods. Standard automated perimetry (SAP) and frequency-domain optical coherence tomography (fdOCT) data, consisting of macular retinal ganglion cell plus inner plexiform layer (mRGCPL) as well as macular and optic disc retinal nerve fiber layer (mRNFL and dRNFL) thicknesses, were collected from 52 eyes of 52 healthy controls and 156 eyes of 96 glaucoma suspects and patients. In addition to generating simple global metrics, SAP and fdOCT data were searched for contiguous clusters of abnormal points and converted to a continuous metric (pcc). The pcc metric, along with simpler methods, was used to combine the information from the SAP and fdOCT. The performance of different methods was assessed using the area under receiver operator characteristic curves (AROC scores). Results. The pcc metric performed better than simple global measures for both the fdOCT and SAP. The best combined structure-function metric (mRGCPL&SAP pcc, AROC = 0.868 ± 0.032) was better (statistically significant) than the best metrics for independent measures of structure and function. When SAP was used as part of the inclusion and exclusion criteria, AROC scores increased for all metrics, including the best combined structure-function metric (AROC = 0.975 ± 0.014). Conclusions. A combined structure-function metric improved the detection of glaucomatous eyes. Overall, the primary sources of value-added for glaucoma detection stem from the continuous cluster search (the pcc), the mRGCPL data, and the combination of structure and function. PMID:24408977

Fasudil, a Clinically Used ROCK Inhibitor, Stabilizes Rod Photoreceptor Synapses after Retinal Detachment.

PubMed

Townes-Anderson, Ellen; Wang, Jianfeng; Halász, Éva; Sugino, Ilene; Pitler, Amy; Whitehead, Ian; Zarbin, Marco

2017-06-01

Retinal detachment disrupts the rod-bipolar synapse in the outer plexiform layer by retraction of rod axons. We showed that breakage is due to RhoA activation whereas inhibition of Rho kinase (ROCK), using Y27632, reduces synaptic damage. We test whether the ROCK inhibitor fasudil, used for other clinical applications, can prevent synaptic injury after detachment. Detachments were made in pigs by subretinal injection of balanced salt solution (BSS) or fasudil (1, 10 mM). In some animals, fasudil was injected intravitreally after BSS-induced detachment. After 2 to 4 hours, retinae were fixed for immunocytochemistry and confocal microscopy. Axon retraction was quantified by imaging synaptic vesicle label in the outer nuclear layer. Apoptosis was analyzed using propidium iodide staining. For biochemical analysis by Western blotting, retinal explants, detached from retinal pigmented epithelium, were cultured for 2 hours. Subretinal injection of fasudil (10 mM) reduced retraction of rod spherules by 51.3% compared to control detachments ( n = 3 pigs, P = 0.002). Intravitreal injection of 10 mM fasudil, a more clinically feasible route of administration, also reduced retraction (28.7%, n = 5, P < 0.05). Controls had no photoreceptor degeneration at 2 hours, but by 4 hours apoptosis was evident. Fasudil 10 mM reduced pyknotic nuclei by 55.7% ( n = 4, P < 0.001). Phosphorylation of cofilin and myosin light chain, downstream effectors of ROCK, was decreased with 30 μM fasudil ( n = 8-10 explants, P < 0.05). Inhibition of ROCK signaling with fasudil reduced photoreceptor degeneration and preserved the rod-bipolar synapse after retinal detachment. These results support the possibility, previously tested with Y27632, that ROCK inhibition may attenuate synaptic damage in iatrogenic detachments.

Predictors of vision impairment in Multiple Sclerosis.

PubMed

Sanchez-Dalmau, Bernardo; Martinez-Lapiscina, Elena H; Pulido-Valdeolivas, Irene; Zubizarreta, Irati; Llufriu, Sara; Blanco, Yolanda; Sola-Valls, Nuria; Sepulveda, Maria; Guerrero, Ana; Alba, Salut; Andorra, Magi; Camos, Anna; Sanchez-Vela, Laura; Alfonso, Veronica; Saiz, Albert; Villoslada, Pablo

2018-01-01

Visual impairment significantly alters the quality of life of people with Multiple Sclerosis (MS). The objective of this study was to identify predictors (independent variables) of visual outcomes, and to define their relationship with neurological disability and retinal atrophy when assessed by optical coherence tomography (OCT). We performed a cross-sectional analysis of 119 consecutive patients with MS, assessing vision using high contrast visual acuity (LogMar), 2.5% and 1.25% low contrast visual acuity (Sloan charts), and color vision (Hardy-Rand-Rittler plates). Quality of vision is a patient reported outcome based on an individual's unique perception of his or her vision and was assessed with the Visual Functioning Questionnaire-25 (VFQ-25) with the 10 neuro-ophthalmologic items. MS disability was assessed using the expanded disability status scale (EDSS), the MS functional composite (MSFC) and the brief repetitive battery-neuropsychology (BRB-N). Retinal atrophy was assessed using spectral domain OCT, measuring the thickness of the peripapillar retinal nerve fiber layer (pRNFL) and the volume of the ganglion cell plus inner plexiform layer (GCIPL). The vision of patients with MS was impaired, particularly in eyes with prior optic neuritis. Retinal atrophy (pRNFL and GCIPL) was closely associated with impaired low contrast vision and color vision, whereas the volume of the GCIPL showed a trend (p = 0.092) to be associated with quality of vision. Multiple regression analysis revealed that EDSS was an explanatory variable for high contrast vision after stepwise analysis, GCIPL volume for low contrast vision, and GCIPL volume and EDSS for color vision. The explanatory variables for quality of vision were high contrast vision and color vision. In summary, quality of vision in MS depends on the impairment of high contrast visual acuity and color vision due to the disease.

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.

Early-Onset, Slow Progression of Cone Photoreceptor Dysfunction and Degeneration in CNG Channel Subunit CNGB3 Deficiency

PubMed Central

Xu, Jianhua; Morris, Lynsie; Fliesler, Steven J.; Sherry, David M.

2011-01-01

Purpose. To investigate the progression of cone dysfunction and degeneration in CNG channel subunit CNGB3 deficiency. Methods. Retinal structure and function in CNGB3−/− and wild-type (WT) mice were evaluated by electroretinography (ERG), lectin cytochemistry, and correlative Western blot analysis of cone-specific proteins. Cone and rod terminal integrity was assessed by electron microscopy and synaptic protein immunohistochemical distribution. Results. Cone ERG amplitudes (photopic b-wave) in CNGB3−/− mice were reduced to approximately 50% of WT levels by postnatal day 15, decreasing further to approximately 30% of WT levels by 1 month and to approximately 20% by 12 months of age. Rod ERG responses (scotopic a-wave) were not affected in CNGB3−/− mice. Average CNGB3−/− cone densities were approximately 80% of WT levels at 1 month and declined slowly thereafter to only approximately 50% of WT levels by 12 months. Expression levels of M-opsin, cone transducin α-subunit, and cone arrestin in CNGB3−/− mice were reduced by 50% to 60% by 1 month and declined to 35% to 45% of WT levels by 9 months. In addition, cone opsin mislocalized to the outer nuclear layer and the outer plexiform layer in the CNGB3−/− retina. Cone and rod synaptic marker expression and terminal ultrastructure were normal in the CNGB3−/− retina. Conclusions. These findings are consistent with an early-onset, slow progression of cone functional defects and cone loss in CNGB3−/− mice, with the cone signaling deficits arising from disrupted phototransduction and cone loss rather than from synaptic defects. PMID:21273547

Assessment of Optical Coherence Tomography Color Probability Codes in Myopic Glaucoma Eyes After Applying a Myopic Normative Database.

PubMed

Seol, Bo Ram; Kim, Dong Myung; Park, Ki Ho; Jeoung, Jin Wook

2017-11-01

To evaluate the optical coherence tomography (OCT) color probability codes based on a myopic normative database and to investigate whether the implementation of the myopic normative database can improve the OCT diagnostic ability in myopic glaucoma. Comparative validity study. In this study, 305 eyes (154 myopic healthy eyes and 151 myopic glaucoma eyes) were included. A myopic normative database was obtained based on myopic healthy eyes. We evaluated the agreement between OCT color probability codes after applying the built-in and myopic normative databases, respectively. Another 120 eyes (60 myopic healthy eyes and 60 myopic glaucoma eyes) were included and the diagnostic performance of OCT color codes using a myopic normative database was investigated. The mean weighted kappa (Kw) coefficients for quadrant retinal nerve fiber layer (RNFL) thickness, clock-hour RNFL thickness, and ganglion cell-inner plexiform layer (GCIPL) thickness were 0.636, 0.627, and 0.564, respectively. The myopic normative database showed a higher specificity than did the built-in normative database in quadrant RNFL thickness, clock-hour RNFL thickness, and GCIPL thickness (P < .001, P < .001, and P < .001, respectively). The receiver operating characteristic curve values increased when using the myopic normative database in quadrant RNFL thickness, clock-hour RNFL thickness, and GCIPL thickness (P = .011, P = .004, P < .001, respectively). The diagnostic ability of OCT color codes for detection of myopic glaucoma significantly improved after application of the myopic normative database. The implementation of a myopic normative database is needed to allow more precise interpretation of OCT color probability codes when used in myopic eyes. Copyright © 2017 Elsevier Inc. All rights reserved.

Calbindin-D28k and calretinin in chicken inner retina during postnatal development and neuroplasticity by dim red light.

PubMed

Fosser, Nicolás Sebastián; Ronco, Laura; Bejarano, Alejandro; Paganelli, Alejandra R; Ríos, Hugo

2013-07-01

Members of the family of calcium binding proteins (CBPs) are involved in the buffering of calcium (Ca2+) by regulating how Ca2+ can operate within synapses or more globally in the entire cytoplasm and they are present in a particular arrangement in all types of retinal neurons. Calbindin D28k and calretinin belong to the family of CBPs and they are mainly co-expressed with other CBPs. Calbindin D28k is expressed in doubles cones, bipolar cells and in a subpopulation of amacrine and ganglion neurons. Calretinin is present in horizontal cells as well as in a subpopulation of amacrine and ganglion neurons. Both proteins fill the soma at the inner nuclear layer and the neuronal projections at the inner plexiform layer. Moreover, calbindin D28k and calretinin have been associated with neuronal plasticity in the central nervous system. During pre and early postnatal visual development, the visual system shows high responsiveness to environmental influences. In this work we observed modifications in the pattern of stratification of calbindin immunoreactive neurons, as well as in the total amount of calbindin through the early postnatal development. In order to test whether or not calbindin is involved in retinal plasticity we analyzed phosphorylated p38 MAPK expression, which showed a decrease in p-p38 MAPK, concomitant to the observed decrease of calbindin D28k. Results showed in this study suggest that calbindin is a molecule related with neuroplasticity, and we suggest that calbindin D28k has significant roles in neuroplastic changes in the retina, when retinas are stimulated with different light conditions. Copyright © 2013 Wiley Periodicals, Inc.

MULTIMODAL IMAGING OF MOSAIC RETINOPATHY IN CARRIERS OF HEREDITARY X-LINKED RECESSIVE DISEASES.

PubMed

Wu, An-Lun; Wang, Jung-Pan; Tseng, Yun-Ju; Liu, Laura; Kang, Yu-Chuan; Chen, Kuan-Jen; Chao, An-Ning; Yeh, Lung-Kun; Chen, Tun-Lu; Hwang, Yih-Shiou; Wu, Wei-Chi; Lai, Chi-Chun; Wang, Nan-Kai

2018-05-01

To investigate the clinical features in carriers of X-linked retinitis pigmentosa, X-linked ocular albinism, and choroideremia (CHM) using multimodal imaging and to assess their diagnostic value in these three mosaic retinopathies. We prospectively examined 14 carriers of 3 X-linked recessive disorders (X-linked retinitis pigmentosa, X-linked ocular albinism, and CHM). Details of abnormalities of retinal morphology were evaluated using fundus photography, fundus autofluorescence (FAF) imaging, and spectral domain optical coherence tomography. In six X-linked retinitis pigmentosa carriers, fundus appearance varied from unremarkable to the presence of tapetal-like reflex and pigmentary changes. On FAF imaging, all carriers exhibited a bright radial reflex against a dark background. By spectral domain optical coherence tomography, loss of the ellipsoid zone in the macula was observed in 3 carriers (50%). Regarding the retinal laminar architecture, 4 carriers (66.7%) showed thinning of the outer nuclear layer and a dentate appearance of the outer plexiform layer. All five X-linked ocular albinism carriers showed a characteristic mud-splatter patterned fundus, dark radial streaks against a bright background on FAF imaging, and a normal-appearing retinal structure by spectral domain optical coherence tomography imaging. Two of the 3 CHM carriers (66.7%) showed a diffuse moth-eaten appearance of the fundus, and all 3 showed irregular hyper-FAF and hypo-FAF spots throughout the affected area. In the CHM carriers, the structural changes observed by spectral domain optical coherence tomography imaging were variable. Our findings in an Asian cohort suggest that FAF imaging is a practical diagnostic test for differentiating X-linked retinitis pigmentosa, X-linked ocular albinism, and CHM carriers. Wide-field FAF is an easy and helpful adjunct to testing for the correct diagnosis and identification of lyonization in carriers of these three mosaic retinopathies.

Vitreal IgM autoantibodies target neurofilament medium in a spontaneous model of autoimmune uveitis.

PubMed

Swadzba, Margarete E; Hirmer, Sieglinde; Amann, Barbara; Hauck, Stefanie M; Deeg, Cornelia A

2012-01-25

Although the presence of IgG autoantibodies in the vitreous of spontaneous cases of equine recurrent uveitis (ERU) has been demonstrated, the potential role of IgM reactivities during ERU pathogenesis remains unexplored. The purpose of this study was to examine the presence of IgM autoantibodies in vitreous specimens of ERU-affected horses and to test their binding specificity to intraocularly expressed proteins. To test IgM autoantibody responses to retinal tissue, vitreous samples of eye-healthy controls and ERU patients were analyzed via two-dimensional Western blot analysis with equine retinal tissue as an antigen source. A candidate protein, the peptide neurofilament medium (NF-M), was identified via mass spectrometry and validated via enzyme-linked immunosorbent assay. Immunohistochemistry for NF-M expression was performed on healthy and ERU-affected retinal sections. Whereas autoreactivity was never detected in the healthy vitreous samples, NF-M was specifically targeted by vitreal IgM autoantibodies in 44% of the ERU cases. Vitreal anti-NF-M IgG was detected in only 8% of the ERU samples, pointing to a persistent IgM response. In healthy horse retina, NF-M was located in the retinal ganglion cells and their processes, with additional staining in the outer plexiform layer. NF-M expression in ERU-affected retinas decreased considerably, and the remaining expression was limited to the nerve fiber layer. Intraocular anti NF-M IgM autoantibodies occur with high prevalence in vitreous of spontaneous autoimmune uveitis cases. The IgM dominated response may indicate a thymus-independent response to NF-M and merits further investigation in ERU, as well as in its human counterpart, autoimmune uveitis.

Peripapillary vessel density changes in Leber's Hereditary Optic Neuropathy: a new biomarker.

PubMed

Balducci, Nicole; Cascavilla, Maria Lucia; Ciardella, Antonio; La Morgia, Chiara; Triolo, Giacinto; Parisi, Vincenzo; Bandello, Francesco; Sadun, Alfredo A; Carelli, Valerio; Barboni, Piero

2018-05-22

The contribution of the microvascular supply to the pathogenesis of Leber's Hereditary Optic Neuropathy (LHON) is poorly understood. We aimed at measuring the peripapillary capillary vessel density (VD) using optical coherence tomography angiography (OCT-A) at different stages of LHON. Prospective, cross-sectional, multicenter, observational study. Twenty-two LHON patients divided in 4 groups: unaffected mutation carriers (LHON-u); early subacute stage (LHON-e); late subacute stage (LHON-l); chronic stage (LHON-ch). OCT-A scans centered on the optic disc were obtained by spectral domain OCT system. VD, retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GC-IPL) thickness were compared between groups. Significant VD changes were detected in every sector (p<0.0001). In LHON-e, the VD was reduced in the temporal sector compared with LHON-u and in the temporal and inferotemporal sectors compared with controls. In LHON-l, VD was reduced in whole, temporal, superotemporal and inferotemporal sectors compared with LHON-u and controls. In LHON-ch, the VD was reduced in all sectors compared to the other groups. An asynchronous pattern emerged in the temporal sector with VD changes occurring earlier than RNFL thickness changes and together with GC-IPL thinning. Significant peripapillary miscrovascular changes were detected over the different stages of LHON. Studying the vascular network separately from fibers revealed that microvascular changes in the temporal sector preceded the changes of RNFL and mirrored the GC-IPL changes. Measurements of the peripapillary vascular network may become a useful biomarker to monitor the disease process, evaluate therapeutic efficacy and elucidate pathophysiology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluation of possible factors affecting contrast sensitivity function in patients with primary Sjögren's syndrome.

PubMed

Arikan, Sedat; Gokmen, Ferhat; Comez, Arzu Taskiran; Gencer, Baran; Kara, Selcuk; Akbal, Ayla

2015-01-01

The contrast sensitivity (CS) function in patients with primary Sjögren's syndrome (pSS) may be impaired either frequently as a result of dry eye diseases or rarely as a result of optic neuropathy. In this study, we aimed to evaluate the CS function in pSS patients as well as to assess corneal aberrations and thickness of the peripapillary retinal nerve fiber layer (pRNFL). Fourteen eyes of 14 pSS patients (pSS group) and 14 eyes of 14 healthy participants (control group) were subjected to assessment of CS at the spatial frequencies of 1.5, 3.0, 6.0, 12, and 18 cycles/degree (cpd) using a functional visual acuity contrast test (FACT); measurement of corneal high-order aberrations (HOAs) in terms of coma-like, spherical-like, and total HOAs using Scheimpflug corneal topography; and measurement of the thickness of both the macular ganglion cell-inner plexiform layer (mGCIPL) and pRNFL in all quadrants using optical coherence tomography. None of the participants were under treatment with artificial tears. The results of the CS test did not differ between the 2 groups at all spatial frequencies (p>0.05). In addition, there were no statistically significant differences between the 2 groups in terms of corneal HOAs (p>0.05) and thickness of mGCIPL (p>0.05). However, among all quadrants, only the inferior quadrant of pRNFL in pSS patients was statistically significantly thinner than that in the healthy participants (p=0.04). The CS function in pSS patients can be maintained with normal thickness of both pRNFL and mGCIPL and with lack of increased corneal HOAs, which may be present even in the absence of artificial tear usage.

The Evaluation of Anatomic and Functional Changes in Unilateral Moderate Amblyopic Eyes Using Optical Coherence Tomography and Pupil Cycle Time.

PubMed

Kusbeci, Tuncay; Karti, Omer; Karahan, Eyyup; Oguztoreli, Mustafa

2017-12-01

To investigate whether macular anatomic structure and afferent visual system function differ among amblyopic eyes, non-amblyopic fellow eyes, and controls, using spectral-domain optical coherence tomography (SD-OCT), and pupil cycle time (PCT). This observational, cross-sectional study included 30 patients with unilateral amblyopia and 30 healthy subjects. Optical coherence tomography (OCT) and pupil cycle time (PCT) were used to evaluate patients with unilateral amblyopia and were compared with their non-amblyopic fellow eyes and age- and gender-matched healthy eyes (30 participants). The amblyopic eyes were separated into two groups: anisometropic amblyopia (n = 16) and strabismic amblyopia (n = 14). OCT maps were used to calculate central macular thickness (CMT), retinal nerve fiber layer thickness (RNFLT), and ganglion cell-inner plexiform layer (GC-IPL) thickness. The average RNFLT, GC-IPL thickness, and CMT did not show any significant differences among the amblyopic eyes, non-amblyopic fellow eyes and controls (p > 0.05, Kruskal-Wallis test). Mean PCT was 773.57 ± 64 msn in strabismic eyes, 771.25 ± 58 msn in anisometropic eyes, 778.00 ± 72 msn in non-amblyopic fellow eyes, and 774.75 ± 69 msn in control eyes. The differences among the amblyopic eyes, its fellow and control eyes were not statistically significant (p > 0.05, Kruskal-Wallis test). In this study, we investigated morphological and functional differences among amblyopic eyes, non-amblyopic fellow eyes and controls by using SD-OCT and PCT. We did not find anatomical or functional changes in amblyopic eyes.

Rapamycin prevents N-methyl-D-aspartate-induced retinal damage through an ERK-dependent mechanism in rats.

PubMed

Ichikawa, Atsuko; Nakahara, Tsutomu; Kurauchi, Yuki; Mori, Asami; Sakamoto, Kenji; Ishii, Kunio

2014-06-01

Recent studies have demonstrated that inhibition of the mammalian target of rapamycin (mTOR) protects against neuronal injury, but the mechanisms underlying this protection are not fully understood. The present study investigates whether rapamycin, an inhibitor of the mTOR pathway, protects against N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity and whether the extracellular signal-regulated kinase (ERK) pathway contributes to this protective effect in rats. Significant cell loss in the ganglion cell layer and a reduction in thickness of the inner plexiform layer were observed 7 days after a single intravitreal injection of NMDA (200 nmol/eye). These NMDA-induced morphological changes were significantly reduced by rapamycin (20 nmol/eye). The number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells had increased 6 hr after NMDA injection, an effect that was significantly attenuated by rapamycin. The ERK inhibitor U0126 (1 nmol/eye) almost completely abolished rapamycin's inhibition of NMDA-induced apoptosis. Immunohistochemical studies showed that NMDA caused a time-dependent increase in levels of the phosphorylated form of the ribosomal protein S6 (pS6), a downstream indicator of mTOR activity. The increased pS6 levels were markedly decreased by rapamycin. Both NMDA and rapamycin increased the level of phosphorylated ERK (pERK) in Müller cells, and coinjection of both agents further increased pERK levels. These results suggest that rapamycin has a neuroprotective effect against NMDA-induced retinal neurotoxicity and that this effect could be patially mediated by activation of the ERK pathway in retinal Müller cells. Copyright © 2014 Wiley Periodicals, Inc.

Mutation of ATF6 causes autosomal recessive achromatopsia.

PubMed

Ansar, Muhammad; Santos-Cortez, Regie Lyn P; Saqib, Muhammad Arif Nadeem; Zulfiqar, Fareeha; Lee, Kwanghyuk; Ashraf, Naeem Mahmood; Ullah, Ehsan; Wang, Xin; Sajid, Sundus; Khan, Falak Sher; Amin-ud-Din, Muhammad; Smith, Joshua D; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Hameed, Abdul; Riazuddin, Saima; Ahmed, Zubair M; Ahmad, Wasim; Leal, Suzanne M

2015-09-01

Achromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3, CNGB3, GNAT2, PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1-q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Glyfs*8) was identified, which completely segregates with the ACHM phenotype within the family. The frameshift variant was absent in public variant databases, in 130 exomes from unrelated Pakistani individuals, and in 235 ethnically matched controls. The variant is predicted to result in a truncated protein that lacks the DNA binding and transmembrane domains and therefore affects the function of ATF6 as a transcription factor that initiates the unfolded protein response during endoplasmic reticulum (ER) stress. Immunolabeling with anti-ATF6 antibodies showed localization throughout the mouse neuronal retina, including retinal pigment epithelium, photoreceptor cells, inner nuclear layer, inner and outer plexiform layers, with a more prominent signal in retinal ganglion cells. In contrast to cytoplasmic expression of wild-type protein, in heterologous cells ATF6 protein with the p.Glu119Glyfs*8 variant is mainly confined to the nucleus. Our results imply that response to ER stress as mediated by the ATF6 pathway is essential for color vision in humans.

Probing the primordial universe with gravitational waves detectors

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

Wang, Yu-Tong; Cai, Yong; Liu, Zhi-Guo

The spectrum of primordial gravitational waves (GWs), especially its tilt n {sub T} , carries significant information about the primordial universe. Combining recent aLIGO and Planck2015+BK14 data, we find that the current limit is n {sub T} =0.016{sup +0.614}{sub −0.989} at 95% C.L. We also estimate the impacts of Einstein Telescope and LISA on constraining n {sub T} . Moreover, based on the effective field theory of cosmological perturbations, we make an attempt to confront some models of early universe scenarios, which produce blue-tilted GWs spectrum ( n {sub T} {sub >0}), with the corresponding datasets.

Primordial perturbations in a rainbow universe with running Newton constant

NASA Astrophysics Data System (ADS)

Brighenti, Francesco; Gubitosi, Giulia; Magueijo, Joao

2017-03-01

We compute the spectral index of primordial perturbations in a rainbow universe. We allow the Newton constant G to run at (super-) Planckian energies and we consider both vacuum and thermal perturbations. If the rainbow metric is the one associated to a generalized Horava-Lifshitz dispersion relation, we find that only when G tends asymptotically to 0 can one match the observed value of the spectral index and solve the horizon problem, both for vacuum and thermal perturbations. For vacuum fluctuations the observational constraints imply that the primordial universe expansion can be both accelerating or decelerating, while in the case of thermal perturbations only decelerating expansion is allowed.

Digging Deeper: Observing Primordial Gravitational Waves below the Binary-Black-Hole-Produced Stochastic Background.

PubMed

Regimbau, T; Evans, M; Christensen, N; Katsavounidis, E; Sathyaprakash, B; Vitale, S

2017-04-14

The merger rate of black hole binaries inferred from the detections in the first Advanced LIGO science run implies that a stochastic background produced by a cosmological population of mergers will likely mask the primordial gravitational wave background. Here we demonstrate that the next generation of ground-based detectors, such as the Einstein Telescope and Cosmic Explorer, will be able to observe binary black hole mergers throughout the Universe with sufficient efficiency that the confusion background can potentially be subtracted to observe the primordial background at the level of Ω_{GW}≃10^{-13} after 5 years of observation.

Mimas: Constraints on Origin and Evolution from Libration Data

NASA Astrophysics Data System (ADS)

Neveu, Marc; Rhoden, Alyssa R.

2016-10-01

In stark contrast with its neighbor moon Enceladus, Mimas is surprisingly geologically quiet, despite an orbital configuration prone to levels of tidal dissipation 30 times higher. While Mimas' lack of activity could be due to a stiff, frigid interior, libration data from the Cassini spacecraft suggest its interior is not homogeneous [1]. Here, we present 1-D models of Mimas' thermal and structural evolution under two accretion scenarios: primordial, undifferentiated formation in the Saturnian subnebula [2]; and late, layered formation from a debris ring created by the disruption of one or more previous moons [3]. In the primordial scenario, our simulations yield two possible outcomes. If tidal dissipation proceeds at levels higher than those obtained using an Andrade rheology [4], Mimas differentiates and an ocean persists until the present day. This should quickly circularize its orbit, but the current orbit is eccentric. In addition, Mimas lacks surface fractures that should result from strong tidal stresses in an ice shell atop an ocean [5]. If dissipation proceeds at lower levels obtained using a Maxwell rheology, it is too weak to drive differentiation; this does not match the observed libration [1]. In the late accretion scenario, Mimas forms already differentiated. As a result, even its deepest ice is within only 100 km of the frigid surface, and poorly insulated by overlying thermally conductive crystalline ice. Thus, all ice remains cold and poorly dissipative, even if dissipation is an order of magnitude above that provided by the Andrade rheology [4]. If Mimas' rocky core is slightly non-hydrostatic [1], this matches the observed libration. We conclude that Mimas' libration is compatible with a late origin from a debris ring, but not with primordial accretion. Consistent with findings from many authors (e.g. [6]), these models cannot produce an ocean on Enceladus unless its orbital eccentricity is higher than observed.References:[1] Tajeddine et al. (2014) Science 346, 322[2] Peale (1999) Annu Rev Astron Astrophys 37, 533[3] Charnoz et al. (2011) Icarus 216, 535[4] McCarthy & Cooper (2016) EPSL 443, 185[5] Rhoden et al., JGR: Planets, submitted[6] Roberts & Nimmo (2008) Icarus 194, 675

The survival of geochemical mantle heterogeneities

NASA Astrophysics Data System (ADS)

Albarede, F.

2004-12-01

The last decade witnessed major changes in our perception of the geochemical dynamics of the mantle. Data bases such as PETDB and GEOROC now provide highly constrained estimates of the geochemical properties of dominant rock types and of their statistics, while the new generation of ICP mass spectrometers triggered a quantum leap in the production of high-precision isotopic and elemental data. Such new advances offer a fresh view of mantle heterogeneities and their survival through convective mixing. A vivid example is provided by the new high-density coverage of the Mid-Atlantic ridge by nearly 500 Pb, Nd, and Hf isotopic data. This new data set demonstrates a rich harmonic structure which illustrates the continuing stretching and refolding of subducted plates by mantle convection. Just as for oceanic chemical variability, the survival of mantle geochemical heterogeneities though mantle circulation can be seen as a competition between stirring and renewal. The modern residence (renewal) times of the incompatible lithophile elements in the mantle calculated using data bases vary within a rather narrow range (4-9 Gy). The mantle is therefore not currently at geochemical steady-state and the effect of its primordial layering on modern mantle geochemistry is still strong. Up to 50 percent of incompatible lithophile elements may never have been extracted into the oceanic crust, which generalizes a conclusion reached previously for 40Ar. A balance between the buoyancy flux and viscous dissipation provides frame-independent estimates of the rates of mixing by mantle convection: primordial geochemical anomalies with initial length scales comparable to mantle depths of plate lengths are only marginally visible at the scale of mantle melting underneath mid-ocean ridges (≈~50~km). They may show up, however, in hot spot basalts and even more in melt inclusions. Up to 50 percent primordial material may be present in the mantle, but scattered throughout as small (<~10~km) domains, strongly sheared and refolded, and interlayered with younger recycled material. The exploration of the fine-scale geochemical structure of the mantle and the quest for preserved remnants of very old mantle arise as the strongest priorities of deep Earth geochemistry.

Renal tubular leakage complicating microcephalic osteodysplastic primordial dwarfism.

PubMed Central

Eason, J; Hall, C M; Trounce, J Q

1995-01-01

We describe a male infant with phenotypic and radiological features of microcephalic osteodysplastic primordial dwarfism type I/III. He showed severe osteoporosis and biochemical derangement owing to renal tubular leakage, which has not previously been reported in this condition. He died aged 5 months. Images PMID:7783178

Exploring the retinal connectome

PubMed Central

Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Shaw, Margaret V.; Yang, Jia-Hui; DeMill, David; Lauritzen, James S.; Lin, Yanhua; Rapp, Kevin D.; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross

2011-01-01

Purpose A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. Methods We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Results Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive axonal veto synapses. (3) Chains of conventional synapses were very common, with intercalated glycinergic-GABAergic chains and very long chains associated with starburst amacrine cells. Glycinergic amacrine cells clearly play a major role in ON-OFF crossover inhibition. (4) Molecular and excitation mapping clearly segregates ultrastructurally defined bipolar cell groups into different response clusters. (5) Finally, low-resolution electron or optical imaging cannot reliably map synaptic connections by process geometry, as adjacency without synaptic contact is abundant in the retina. Only direct visualization of synapses and gap junctions suffices. Conclusions Connectome assembly and analysis using conventional transmission electron microscopy is now practical for network discovery. Our surveys of volume RC1 demonstrate that previously studied systems such as the AII amacrine cell network involve more network motifs than previously known. The AII network, primarily considered a scotopic pathway, clearly derives ribbon synapse input from photopic ON and OFF cone bipolar cell networks and extensive photopic GABAergic amacrine cell inputs. Further, bipolar cells show extensive inputs and outputs along their axons, similar to multistratified nonmammalian bipolar cells. Physiologic evidence of significant ON-OFF channel crossover is strongly supported by our anatomic data, showing alternating glycine-to-GABA paths. Long chains of amacrine cell networks likely arise from homocellular GABAergic synapses between starburst amacrine cells. Deeper analysis of RC1 offers the opportunity for more complete descriptions of specific networks. PMID:21311605

Exploring the retinal connectome.

PubMed

Anderson, James R; Jones, Bryan W; Watt, Carl B; Shaw, Margaret V; Yang, Jia-Hui; Demill, David; Lauritzen, James S; Lin, Yanhua; Rapp, Kevin D; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross; Marc, Robert E

2011-02-03

A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈ 2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive axonal veto synapses. (3) Chains of conventional synapses were very common, with intercalated glycinergic-GABAergic chains and very long chains associated with starburst amacrine cells. Glycinergic amacrine cells clearly play a major role in ON-OFF crossover inhibition. (4) Molecular and excitation mapping clearly segregates ultrastructurally defined bipolar cell groups into different response clusters. (5) Finally, low-resolution electron or optical imaging cannot reliably map synaptic connections by process geometry, as adjacency without synaptic contact is abundant in the retina. Only direct visualization of synapses and gap junctions suffices. Connectome assembly and analysis using conventional transmission electron microscopy is now practical for network discovery. Our surveys of volume RC1 demonstrate that previously studied systems such as the AII amacrine cell network involve more network motifs than previously known. The AII network, primarily considered a scotopic pathway, clearly derives ribbon synapse input from photopic ON and OFF cone bipolar cell networks and extensive photopic GABAergic amacrine cell inputs. Further, bipolar cells show extensive inputs and outputs along their axons, similar to multistratified nonmammalian bipolar cells. Physiologic evidence of significant ON-OFF channel crossover is strongly supported by our anatomic data, showing alternating glycine-to-GABA paths. Long chains of amacrine cell networks likely arise from homocellular GABAergic synapses between starburst amacrine cells. Deeper analysis of RC1 offers the opportunity for more complete descriptions of specific networks.

Expression of GFP under the control of the RNA helicase VASA permits fluorescence-activated cell sorting isolation of human primordial germ cells.

PubMed

Tilgner, Katarzyna; Atkinson, Stuart P; Yung, Sun; Golebiewska, Anna; Stojkovic, Miodrag; Moreno, Ruben; Lako, Majlinda; Armstrong, Lyle

2010-01-01

The isolation of significant numbers of human primordial germ cells at several developmental stages is important for investigations of the mechanisms by which they are able to undergo epigenetic reprogramming. Only small numbers of these cells can be obtained from embryos of appropriate developmental stages, so the differentiation of human embryonic stem cells is essential to obtain sufficient numbers of primordial germ cells to permit epigenetic examination. Despite progress in the enrichment of human primordial germ cells using fluorescence-activated cell sorting (FACS), there is still no definitive marker of the germ cell phenotype. Expression of the widely conserved RNA helicase VASA is restricted to germline cells, but in contrast to species such as Mus musculus in which reporter constructs expressing green fluorescent protein (GFP) under the control of a Vasa promoter have been developed, such reporter systems are lacking in human in vitro models. We report here the generation and characterization of human embryonic stem cell lines stably carrying a VASA-pEGFP-1 reporter construct that expresses GFP in a population of differentiating human embryonic stem cells that show expression of characteristic markers of primordial germ cells. This population shows a different pattern of chromatin modifications to those obtained by FACS enrichment of Stage Specific Antigen one expressing cells in our previous publication.

Probing Seismically Melting Induced Mantle Heterogeneities in Thermal-chemical Convection Models

NASA Astrophysics Data System (ADS)

Heck, H. V.; Davies, H.; Nowacki, A.; Wookey, J. M.

2015-12-01

Two regions at the base of the Earth's mantle (the Large Low-Shear Velocity Provinces) pose a fundamental problem in understanding large-scale mantle dynamics and history. Are they dense piles of (possibly primordial) material separated from mantle circulation, or large-scale thermal features which are part of global mantle convection? Or some combination of the two? We use our numerical 3D spherical mantle convection code to perform simulations of the Earths mantle dynamical evolution. We drive the surface velocity of the model according to 200 Ma plate motion reconstructions, to arrive at Earth-like structures in the mantle at present day. Variations in bulk chemistry will be tracked in two ways: 1) by starting the calculations with a (primordial) dense layer at the base of the mantle, and 2) by tracking basalt fraction which is fractionated upon melting close to the surface. The resulting distribution of chemical heterogeneity and temperature will be converted to seismic velocities. This will be done with a thermodynamical database (Stixrude & Lithgow-Bertelloni, GJI, 2005, 2011), allowing us to compare the model with previous observations of triplications and waveform complexity near the margins of the LLSVPs. These observations have been taken as proof that strong chemical variations are present; our simulations can be used to show whether this is true, or if purely thermal convection can also cause these features. We simulate finite-frequency, 3D seismograms at ~5 s period and compare these with previous studies.

Multiple spinal nerve enlargement and SOS1 mutation: Further evidence of overlap between neurofibromatosis type 1 and Noonan phenotype.

PubMed

Santoro, C; Giugliano, T; Melone, M A B; Cirillo, M; Schettino, C; Bernardo, P; Cirillo, G; Perrotta, S; Piluso, G

2018-01-01

Neurofibromatosis type 1 (NF1) has long been considered a well-defined, recognizable monogenic disorder, with neurofibromas constituting a pathognomonic sign. This dogma has been challenged by recent descriptions of patients with enlarged nerves or paraspinal tumors, suggesting that neurogenic tumors and hypertrophic neuropathy may be a complication of Noonan syndrome with multiple lentigines (NSML) or RASopathy phenotype. We describe a 15-year-old boy, whose mother previously received clinical diagnosis of NF1 due to presence of bilateral cervical and lumbar spinal lesions resembling plexiform neurofibromas and features suggestive of NS. NF1 molecular analysis was negative in the mother. The boy presented with Noonan features, multiple lentigines and pectus excavatum. Next-generation sequencing analysis of all RASopathy genes identified p.Ser548Arg missense mutation in SOS1 in the boy, confirmed in his mother. Brain and spinal magnetic resonance imaging scans were negative in the boy. No heart involvement or deafness was observed in proband or mother. This is the first report of a SOS1 mutation associated with hypertrophic neuropathy resembling plexiform neurofibromas, a rare complication in Noonan phenotypes with mutations in RASopathy genes. Our results highlight the overlap between RASopathies, suggesting that NF1 diagnostic criteria need rethinking. Genetic analysis of RASopathy genes should be considered when diagnosis is uncertain. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Orbital/Peri-Orbital Plexiform Neurofibromas in Children with Neurofibromatosis type 1: Multi-disciplinary Recommendations for Care

PubMed Central

Avery, Robert A.; Katowitz, James A.; Fisher, Michael J.; Heidary, Gena; Dombi, Eva; Packer, Roger J.; Widemann, Brigitte C.

2016-01-01

Children and adults with Neurofibromatosis type 1 (NF1), a common autosomal dominant condition, manifest a variety of ophthalmologic conditions. Plexiform neurofibromas involving the eyelid, orbit, periorbital and facial structures (termed OPPN) can result in significant visual loss in children. Equally important, OPPNs can cause significant alteration in physical appearance secondary to proptosis, ptosis, and facial disfigurement, leading to social embarrassment and decreased self-esteem. Despite NF1 being a relatively common disease in which routine ophthalmologic examinations are required, no formal recommendations for clinical care of children with OPPNs exist. While medical and surgical interventions have been reported, there are no agreed upon criteria for when OPPN require therapy and which treatment produces the best outcome. Since a multi-disciplinary team of specialists (oculofacial plastics, pediatric ophthalmology, neuro-ophthalmology, medical genetics and neuro-oncology) direct management decisions, the absence of a uniform outcome measure that represents visual and or aesthetic sequelae complicates the design of evidence based studies and feasible clinical trials. In September 2013, a multi-disciplinary task force, composed of pediatric practitioners from tertiary care centers experienced in caring for children with OPPN, was convened to address the lack of clinical care guidelines for children with OPPN. This consensus statement provides recommendations for ophthalmologic monitoring and outlines treatment indications, forthcoming biologic therapy, while also discussing challenges to performing clinical trials in this complicated condition. PMID:27817916

Hypercellular round cell liposarcoma: A comprehensive cytomorphologic study and review of 8 cases.

PubMed

Chufal, Sanjay S; Chufal, Kundan S; Pant, Prabhat; Rizvi, Ghazala; Pandey, Hari S; Shahi, Kedar S

2017-01-01

Myxoid and round cell liposarcomas (RCL) are low and high-grade counterparts of a common subtype of liposarcomas (LPS), representing a histologic continuum. The aim was to study the cytomorphology of hypercellular RCL and to look for features that differentiate RCL from other sarcomas displaying round cells with myxoid change. Eight cases of hypercellular RCL were identified retrospectively in which round cell component constituted greater than 75% of the area. Cytomorphological features were studied in detail. Four cases were predominantly composed of round cells, out of which 2 were entirely composed of round cells. Myxoid metachromatic stroma was absent in 2 cases, while it was present in ample amounts in the remaining 6 cases. Spindle cells were completely absent in 5 cases and lipoblasts were observed in a single case of RCL. Plexiform vascular capillaries were seen in 4 cases. Adherence of neoplastic round cells around thin capillaries (ANAC) was observed in 7 cases. Plexiform capillary plexus and ANAC should be separately evaluated. The latter feature is the most consistent one, and is an important clue to the adipocytic nature of the neoplasm when hypercellular round cell areas are aspirated. Confident diagnosis of hypercellular RCL can be made on the basis of this feature. Lipoblasts, although specific, are seen in few cases. The rest of the features are nonspecific and useful only in combination.

Telomere erosion in NF1 tumorigenesis.

PubMed

Jones, Rhiannon E; Grimstead, Julia W; Sedani, Ashni; Baird, Duncan; Upadhyaya, Meena

2017-06-20

Neurofibromatosis type 1 (NF1; MIM# 162200) is a familial cancer syndrome that affects 1 in 3,500 individuals worldwide and is inherited in an autosomal dominant fashion. Malignant Peripheral Nerve Sheath Tumors (MPNSTs) represent a significant cause of morbidity and mortality in NF1 and currently there is no treatment or definite prognostic biomarkers for these tumors. Telomere shortening has been documented in numerous tumor types. Short dysfunctional telomeres are capable of fusion and it is considered that the ensuing genomic instability may facilitate clonal evolution and the progression to malignancy. To evaluate the potential role of telomere dysfunction in NF1-associated tumors, we undertook a comparative analysis of telomere length in samples derived from 10 cutaneous and 10 diffused plexiform neurofibromas, and 19 MPNSTs. Telomere length was determined using high-resolution Single Telomere Length Analysis (STELA). The mean Xp/Yp telomere length detected in MPNSTs, at 3.282 kb, was significantly shorter than that observed in both plexiform neurofibromas (5.793 kb; [p = 0.0006]) and cutaneous neurofibromas (6.141 kb; [p = 0.0007]). The telomere length distributions of MPNSTs were within the length-ranges in which telomere fusion is detected and that confer a poor prognosis in other tumor types. These data indicate that telomere length may play a role in driving genomic instability and clonal progression in NF1-associated MPNSTs.

Squeezed states in the theory of primordial gravitational waves

NASA Technical Reports Server (NTRS)

Grishchuk, Leonid P.

1992-01-01

It is shown that squeezed states of primordial gravitational waves are inevitably produced in the course of cosmological evolution. The theory of squeezed gravitons is very similar to the theory of squeezed light. Squeezed parameters and statistical properties of the expected relic gravity-wave radiation are described.

Cutaneous features associated with microcephalic osteodysplastic primordial dwarfism type II.

PubMed

Webber, Naomi; O'Toole, Edel A; Paige, David G; Rosser, Elisabeth

2008-01-01

We present an 18-month-old Pakistani girl who had short stature, craniofacial dysmorphism, and multiple café-au-lait spots. After consultation with the geneticists, microcephalic osteodysplastic primordial dwarfism type II was diagnosed (MIM210720). The presence of consanguinity in reported families is suggestive of autosomal recessive inheritance.

The Primordial Inflation Polarization Explorer (PIPER)

NASA Technical Reports Server (NTRS)

Kogut, Alan J.

2012-01-01

The Primordial Inflation Polarization Explorer (PIPER) is a balloon-borne instrument to measure the gravity-wave signature of primordial inflation through its distinctive imprint on the polarization of the cosmic microwave background. PIPER combines cold (1.5 K) optics, 5120 bolometric detectors, and rapid polarization modulation using VPM grids to achieve both high sensitivity and excellent control of systematic errors. A series of flights alternating between northern and southern hemisphere launch sites will produce maps in Stokes I, Q, U, and V parameters at frequencies 200, 270, 350, and 600 GHz (wavelengths 1500, 1100, 850, and 500 microns) covering 85% of the sky. We describe the PIPER instrument and discuss the current status and expected science returns from the mission.

Mutations in XRCC4 cause primordial dwarfism without causing immunodeficiency.

PubMed

Saito, Shinta; Kurosawa, Aya; Adachi, Noritaka

2016-08-01

In successive reports from 2014 to 2015, X-ray repair cross-complementing protein 4 (XRCC4) has been identified as a novel causative gene of primordial dwarfism. XRCC4 is indispensable for non-homologous end joining (NHEJ), the major pathway for repairing DNA double-strand breaks. As NHEJ is essential for V(D)J recombination during lymphocyte development, it is generally believed that abnormalities in XRCC4 cause severe combined immunodeficiency. Contrary to expectations, however, no overt immunodeficiency has been observed in patients with primordial dwarfism harboring XRCC4 mutations. Here, we describe the various XRCC4 mutations that lead to disease and discuss their impact on NHEJ and V(D)J recombination.

Primordial cosmology in mimetic born-infeld gravity

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

Bouhmadi-Lopez, Mariam; Chen, Che -Yu; Chen, Pisin

Here, the Eddington-inspired-Born-Infeld (EiBI) model is reformulated within the mimetic approach. In the presence of a mimetic field, the model contains non-trivial vacuum solutions which could be free of spacetime singularity because of the Born-Infeld nature of the theory. We study a realistic primordial vacuum universe and prove the existence of regular solutions, such as primordial inflationary solutions of de Sitter type or bouncing solutions. Besides, the linear instabilities present in the EiBI model are found to be avoidable for some interesting bouncing solutions in which the physical metric as well as the auxiliary metric are regular at the backgroundmore » level.« less

Primordial cosmology in mimetic born-infeld gravity

DOE PAGES

Bouhmadi-Lopez, Mariam; Chen, Che -Yu; Chen, Pisin

2017-11-29

Here, the Eddington-inspired-Born-Infeld (EiBI) model is reformulated within the mimetic approach. In the presence of a mimetic field, the model contains non-trivial vacuum solutions which could be free of spacetime singularity because of the Born-Infeld nature of the theory. We study a realistic primordial vacuum universe and prove the existence of regular solutions, such as primordial inflationary solutions of de Sitter type or bouncing solutions. Besides, the linear instabilities present in the EiBI model are found to be avoidable for some interesting bouncing solutions in which the physical metric as well as the auxiliary metric are regular at the backgroundmore » level.« less

Stochastic Gravitational-Wave Background due to Primordial Binary Black Hole Mergers.

PubMed

Mandic, Vuk; Bird, Simeon; Cholis, Ilias

2016-11-11

Recent Advanced LIGO detections of binary black hole mergers have prompted multiple studies investigating the possibility that the heavy GW150914 binary system was of primordial origin, and hence could be evidence for dark matter in the form of black holes. We compute the stochastic background arising from the incoherent superposition of such primordial binary black hole systems in the Universe and compare it to the similar background spectrum due to binary black hole systems of stellar origin. We investigate the possibility of detecting this background with future gravitational-wave detectors, and conclude that constraining the dark matter component in the form of black holes using stochastic gravitational-wave background measurements will be very challenging.

Organogenesis of heart-vascular system derived from mouse 2 cell stage embryos and from early embryonic stem cells in vitro.

PubMed

Ishiwata, Isamu; Tamagawa, Tomoharu; Tokieda, Yuko; Iguchi, Megumi; Sato, Kahei; Ishikawa, Hiroshi

2003-03-01

Regenerative medical treatment with embryonic stem cells (an ES cell) is a goal for organ transplantation. Structures that are tubular in nature (i.e. blood capillaries) were induced from early embryonic stem (EES) cells in vitro using embryotrophic factor (ETFs). In addition, cardiac muscle cells could be identified as well. However, differentiation of EES cells into a complete cardiovascular system was difficult because 3 germ layer primordial organs are directed embryologically in various ways and it is not possible to guide only cardiovascular organs. Thus, we introduced ETFs after the formation of an embryoid body and were successful in cloning cell clusters that beat, thus deriving only cardiovascular organs. The application of this to the treatment of various cardiovascular diseases is promising.

The role of impacting processes in the chemical evolution of the atmosphere of primordial Earth

NASA Technical Reports Server (NTRS)

Mukhin, Lev M.; Gerasimov, M. V.

1991-01-01

The role of impacting processes in the chemical evolution of the atmosphere of primordial Earth is discussed. The following subject areas are covered: (1) Earth's initial atmosphere; (2) continuous degassing; (3) impact processes and the Earth's protoatmosphere; and (4) the evolution of an impact-generated atmosphere.

Probing primordial features with future galaxy surveys

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

Ballardini, M.; Fedeli, C.; Moscardini, L.

2016-10-01

We study the capability of future measurements of the galaxy clustering power spectrum to probe departures from a power-law spectrum for primordial fluctuations. On considering the information from the galaxy clustering power spectrum up to quasi-linear scales, i.e. k < 0.1 h Mpc{sup −1}, we present forecasts for DESI, Euclid and SPHEREx in combination with CMB measurements. As examples of departures in the primordial power spectrum from a simple power-law, we consider four Planck 2015 best-fits motivated by inflationary models with different breaking of the slow-roll approximation. At present, these four representative models provide an improved fit to CMB temperaturemore » anisotropies, although not at statistical significant level. As for other extensions in the matter content of the simplest ΛCDM model, the complementarity of the information in the resulting matter power spectrum expected from these galaxy surveys and in the primordial power spectrum from CMB anisotropies can be effective in constraining cosmological models. We find that the three galaxy surveys can add significant information to CMB to better constrain the extra parameters of the four models considered.« less

Two- and Three-Dimensional Probes of Parity in Primordial Gravity Waves.

PubMed

Masui, Kiyoshi Wesley; Pen, Ue-Li; Turok, Neil

2017-06-02

We show that three-dimensional information is critical to discerning the effects of parity violation in the primordial gravity-wave background. If present, helical gravity waves induce parity-violating correlations in the cosmic microwave background (CMB) between parity-odd polarization B modes and parity-even temperature anisotropies (T) or polarization E modes. Unfortunately, EB correlations are much weaker than would be naively expected, which we show is due to an approximate symmetry resulting from the two-dimensional nature of the CMB. The detectability of parity-violating correlations is exacerbated by the fact that the handedness of individual modes cannot be discerned in the two-dimensional CMB, leading to a noise contribution from scalar matter perturbations. In contrast, the tidal imprints of primordial gravity waves fossilized into the large-scale structure of the Universe are a three-dimensional probe of parity violation. Using such fossils the handedness of gravity waves may be determined on a mode-by-mode basis, permitting future surveys to probe helicity at the percent level if the amplitude of primordial gravity waves is near current observational upper limits.

Primordial anisotropies in gauged hybrid inflation

NASA Astrophysics Data System (ADS)

Akbar Abolhasani, Ali; Emami, Razieh; Firouzjahi, Hassan

2014-05-01

We study primordial anisotropies generated in the model of gauged hybrid inflation in which the complex waterfall field is charged under a U(1)gauge field. Primordial anisotropies are generated either actively during inflation or from inhomogeneities modulating the surface of end of inflation during waterfall transition. We present a consistent δN mechanism to calculate the anisotropic power spectrum and bispectrum. We show that the primordial anisotropies generated at the surface of end of inflation do not depend on the number of e-folds and therefore do not produce dangerously large anisotropies associated with the IR modes. Furthermore, one can find the parameter space that the anisotropies generated from the surface of end of inflation cancel the anisotropies generated during inflation, therefore relaxing the constrains on model parameters imposed from IR anisotropies. We also show that the gauge field fluctuations induce a red-tilted power spectrum so the averaged power spectrum from the gauge field can change the total power spectrum from blue to red. Therefore, hybrid inflation, once gauged under a U(1) field, can be consistent with the cosmological observations.

The intrinsic B-mode polarisation of the Cosmic Microwave Background

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

Fidler, Christian; Pettinari, Guido W.; Crittenden, Robert

2014-07-01

We estimate the B-polarisation induced in the Cosmic Microwave Background by the non-linear evolution of density perturbations. Using the second-order Boltzmann code SONG, our analysis incorporates, for the first time, all physical effects at recombination. We also include novel contributions from the redshift part of the Boltzmann equation and from the bolometric definition of the temperature in the presence of polarisation. The remaining line-of-sight terms (lensing and time-delay) have previously been studied and must be calculated non-perturbatively. The intrinsic B-mode polarisation is present independent of the initial conditions and might contaminate the signal from primordial gravitational waves. We find thismore » contamination to be comparable to a primordial tensor-to-scalar ratio of r ≅ 10{sup −7} at the angular scale ℓ ≅ 100, where the primordial signal peaks, and r ≅ 5 × 10{sup −5} at ℓ ≅ 700, where the intrinsic signal peaks. Therefore, we conclude that the intrinsic B-polarisation from second-order effects is not likely to contaminate future searches of primordial gravitational waves.« less

RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans

PubMed Central

Shamseldin, Hanan; Alazami, Anas M.; Manning, Melanie; Hashem, Amal; Caluseiu, Oana; Tabarki, Brahim; Esplin, Edward; Schelley, Susan; Innes, A. Micheil; Parboosingh, Jillian S.; Lamont, Ryan; Majewski, Jacek; Bernier, Francois P.; Alkuraya, Fowzan S.

2015-01-01

Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963∗] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. PMID:26608784

Chameleon-photon mixing in a primordial magnetic field

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

Schelpe, Camilla A. O.

2010-08-15

The existence of a sizable, O(10{sup -10}-10{sup -9} G), cosmological magnetic field in the early Universe has been postulated as a necessary step in certain formation scenarios for the large-scale O({mu}G) magnetic fields found in galaxies and galaxy clusters. If this field exists then it may induce significant mixing between photons and axion-like particles (ALPs) in the early Universe. The resonant conversion of photons into ALPs in a primordial magnetic field has been studied elsewhere by Mirizzi, Redondo and Sigl (2009). Here we consider the nonresonant mixing between photons and scalar ALPs with masses much less than the plasma frequencymore » along the path, with specific reference to the chameleon scalar field model. The mixing would alter the intensity and polarization state of the cosmic microwave background (CMB) radiation. We find that the average modification to the CMB polarization modes is negligible. However the average modification to the CMB intensity spectrum is more significant and we compare this to high-precision measurements of the CMB monopole made by the far infrared absolute spectrophotometer on board the COBE satellite. The resulting 95% confidence limit on the scalar-photon conversion probability in the primordial field (at 100 GHz) is P{sub {gamma}{r_reversible}{phi}<}2.6x10{sup -2}. This corresponds to a degenerate constraint on the photon-scalar coupling strength, g{sub eff}, and the magnitude of the primordial magnetic field. Taking the upper bound on the strength of the primordial magnetic field derived from the CMB power spectra, B{sub {lambda}{<=}5}.0x10{sup -9} G, this would imply an upper bound on the photon-scalar coupling strength in the range g{sub eff} < or approx. 7.14x10{sup -13} GeV{sup -1} to g{sub eff} < or approx. 9.20x10{sup -14} GeV{sup -1}, depending on the power spectrum of the primordial magnetic field.« less

Closed System Step Etching of CI chondrite Ivuna reveals primordial noble gases in the HF-solubles

NASA Astrophysics Data System (ADS)

Riebe, My E. I.; Busemann, Henner; Wieler, Rainer; Maden, Colin

2017-05-01

We analyzed all the noble gases in HF-soluble phases in the CI chondrite Ivuna by in-vacuum gas release using the "Closed System Step Etching" (CSSE) technique, which allows for direct noble gas measurements of acid-soluble phases. The main motivation was to investigate if there are primordial noble gases in HF-soluble phases in Ivuna, something that has not been done before in CI chondrites, as most primordial noble gases are known to reside in HF-resistant phases. The first steps under mild etching released He, Ne, and Ar with solar-like elemental and isotopic compositions, confirming that Ivuna contains implanted solar wind (SW) noble gases acquired in the parent body regolith. The SW component released in some etch steps was elementally unfractionated. This is unusual as trapped SW noble gases are elementally fractionated in most meteoritic material. In the intermediate etch steps under slightly harsher etching, cosmogenic noble gases were more prominent than SW noble gases. The HF-soluble portion of Ivuna contained primordial Ne and Xe, that was most visible in the last etch steps after all cosmogenic and most SW gases had been released. The primordial Ne and Xe in the HF-solubles have isotopic and elemental ratios readily explained as a mixture of the two most abundant primordial noble gas components in Ivuna bulk samples: HL and Q. Only small fractions of the total HL and Q in Ivuna were released during CSSE analysis; ∼3% of 20NeHL and ∼4% of 132XeQ. HL is known to reside in nanodiamond-rich separates and Q-gases are most likely carried by a carbonaceous phase known as phase Q. Q-gases were likely released from an HF-soluble portion of phase Q. However, nanodiamonds might not be the source of the HL-gases released upon etching, since nanodiamond-rich separates are very HF-resistant and the less tightly bound nanodiamond component P3 was not detected.

Rapamycin Prevents cyclophosphamide-induced Over-activation of Primordial Follicle pool through PI3K/Akt/mTOR Signaling Pathway in vivo.

PubMed

Zhou, Linyan; Xie, Yanqiu; Li, Song; Liang, Yihua; Qiu, Qi; Lin, Haiyan; Zhang, Qingxue

2017-08-16

Primordial follicular depletion has thought to be a common adverse effect of chemotherapy especially for female of reproductive age. The study aimed to evaluate the protective effect of rapamycin on the primordial follicles and its potential mechanism for patients receiving chemotherapy. 8-week old BALB/c female mice were randomly assigned into four groups (control; rapamycin; cyclophosphamide; and rapamycin combined with cyclophosphamide). Hematoxylin staining, immunohistochemical, TUNEL, western blotting and ELISA were employed to assess inter-group differences using Student's t-test and Mann-Whitney test. Cyclophosphamide depleted the follicular reserve and induced the phosphorylation of the key proteins of PI3K/Akt/mTOR pathway in mice in a dose-dependent manner. Co-treatment with rapamycin significantly reduced primordial follicle loss at all cyclophosphamide dose groups and prevent the follicle growth wave caused by cyclophosphamide treatment (P < 0.05). TUNEL staining showed that no apoptosis occured in the primordial follicles in all groups and fewer apoptosis in large growing follicles were observed in ovaries from rapamycin + cyclophosphamide group compared to that received cyclophosphamide alone. Serum anti-Müllerian hormone (AMH) was significantly reduced in cyclophosphamide alone group, in contrast to the normal level in rapamycin + cyclophosphamide group. Compared to p-Akt/Akt and p-mtor/mtor, p-rps6/rps6 was significantly decreased in rapamycin + cyclophosphamide group (P < 0.05), indicating that rapamycin attenuated the increased level of phosphorylation of rpS6 after cyclophosphamide treatment. Rapamycin can prevent the primordial follicle activation induced by cyclophosphamide through PI3K/Akt/mTOR signaling pathway and thus plays a role in preserving the follicle pool. These results suggest that rapamycin may be an effective protection for ovarian function during chemotherapy, which means a new nonsurgical application for protection of ovarian reserve and prevention of POF.

[Fibrohistiocytic tumors of the skin: a heterogeneous group of superficially located mesenchymal neoplasms].

PubMed

Mentzel, T

2015-02-01

So-called fibrohistiocytic tumors of the skin comprise a heterogeneous spectrum of superficially located neoplasms that often show fibroblastic and/or myofibroblastic differentiation. In this review clinicopathologically important variants of dermatofibroma and dermatofibrosarcoma protuberans and their differential diagnoses are discussed in detail. In addition, the clinicopathological features of atypical fibroxanthoma, angiomatoid fibrous histiocytoma, plexiform fibrohistiocytic tumors and pleomorphic dermal sarcoma are presented. Entities that have to be considered in the differential diagnosis are also mentioned.

Osteodysplastic primordial dwarfism: report of a further patient with manifestations similar to those seen in patients with types I and III.

PubMed

Winter, R M; Wigglesworth, J; Harding, B N

1985-07-01

We describe a female infant with low birthweight osteodysplastic microcephalic dwarfism. The child has many manifestations in common with those seen in osteodysplastic primordial dwarfism types I and III. The classification of this heterogeneous group of disorders is discussed in the light of the above case.

Rewarming the Primordial Soup: Revisitations and Rediscoveries in Prebiotic Chemistry.

PubMed

Saladino, Raffaele; Šponer, Judit E; Šponer, Jiří; Di Mauro, Ernesto

2018-01-04

A short history of Campbell's primordial soup: In this essay we try to disclose some of the historical connections between the studies that have contributed to our current understanding of the emergence of catalytic RNA molecules and their components from an inanimate matter. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Gamma rays and energetic particles from primordial black holes

NASA Technical Reports Server (NTRS)

Halzen, F.; Zas, E.; Macgibbon, J. H.; Weekes, T. C.

1991-01-01

The standard model of quarks and leptons is used to discuss the signatures of black-hole evaporations. A firm bound on the primordial black hole abundance is obtained from MeV data. It is argued that the MeV bound can be improved by exploiting the new generation of TeV and PeV telescopes.

Formation of primordial black holes from non-Gaussian perturbations produced in a waterfall transition

NASA Astrophysics Data System (ADS)

Bugaev, Edgar; Klimai, Peter

2012-05-01

We consider the process of primordial black hole (PBH) formation originated from primordial curvature perturbations produced during waterfall transition (with tachyonic instability), at the end of hybrid inflation. It is known that in such inflation models, rather large values of curvature perturbation amplitudes can be reached, which can potentially cause a significant PBH production in the early Universe. The probability distributions of density perturbation amplitudes in this case can be strongly non-Gaussian, which requires a special treatment. We calculated PBH abundances and PBH mass spectra for the model and analyzed their dependence on model parameters. We obtained the constraints on the parameters of the inflationary potential, using the available limits on βPBH.

To Collapse or not to Collapse: The Life of a Primordial Black Hole

NASA Astrophysics Data System (ADS)

Craig, Robert; Bloomfield, Jolyon; Face, Stephen

2016-03-01

Primordial black holes offer insights into topics ranging from cosmological questions about inflationary models to astrophysical questions regarding supermassive black holes. Such insights depend on being able to predict the number density of black holes that form from primordial fluctuations. Traditionally this has been done by means of a ``rule-of-thumb'' developed by Carr in the 1980s, but recent numerical studies have shown that this predictor is a coarse tool at best. We present a two-parameter predictor with much more discrimination power that can be straightforwardly used to compute number densities. We also discuss challenges that face this type of prediction strategy, both analytically and numerically, and possible ways to circumvent them.

Preservation of Primordial Mantle in the Aftermath of a Giant Impact

NASA Astrophysics Data System (ADS)

Lock, S. J.; Stewart, S. T.; Mukhopadhyay, S.

2016-12-01

Terrestrial planets experience a number of giant impacts in the final stages of accretion. These highly energetic events force planets into hot, partially vaporized, and occasionally rapidly-rotating states. However, recent measurements of Xe and W isotopes in mantle plume-derived basalts imply that the terrestrial mantle was not homogenized during this violent stage of Earth's accretion. Understanding the physical structure of post-impact states is key for interpreting these primitive mantle signatures. Post-impact states are highly thermally stratified: the lowermost mantle has lower entropy than the rest of the mantle. Usually, the lowermost mantle is near the solidus or partially molten. The high-entropy portion of the mantle is super-liquidus, smoothly grading to a silicate vapor atmosphere. Here, we consider the competing processes acting on these distinct layers as the mantle establishes a single thermal gradient. If the whole mantle chemically mixed during cooling, then any pre-impact chemical signature would be erased. Previous work has neglected the critical time period between the highly vaporized post-impact state and a fully-condensed silicate body, i.e., a separated magma ocean and atmosphere. The post-impact structure cools rapidly by radiation from the photosphere, causing contraction of the body and redistribution of mass and angular momentum. One consequence of contraction is that the pressure in the mantle increases significantly (on the order of several to 10s GPa at the core mantle boundary) over 10s-1000s years. The increased pressure causes part of the mantle to solidify. Significantly, the timescale for pressure-induced freezing is shorter than the timescale for thermal equilibration between the low and high entropy mantle layers and the timescale for melt percolation (both >100s yrs). Therefore, pressure-induced freezing in the aftermath of a giant impact may be an important factor in preserving primordial Xe and W signatures in the lower mantle. Pressure-induced freezing of the lower mantle predicts a different chemistry than that produced by fractional crystallization of a magma ocean. The post-impact planet could inherit chemical signatures from portions of the mantles of the impacting bodies that did not re-equilibrate with the metal core or outgas volatiles.

Can a grain size-dependent viscosity help yielding realistic seismic velocities of LLSVPs?

NASA Astrophysics Data System (ADS)

Schierjott, J.; Cheng, K. W.; Rozel, A.; Tackley, P. J.

2017-12-01

Seismic studies show two antipodal regions of low shear velocity at the core-mantle boundary (CMB), one beneath the Pacific and one beneath Africa. These regions, called Large Low Shear Velocity Provinces (LLSVPs), are thought to be thermally and chemically distinct and thus have a different density and viscosity. Whereas there is some general consensus about the density of the LLSVPs the viscosity is still a very debated topic. So far, in numerical studies the viscosity is treated as either depth- and/or temperature- dependent but the potential grain size- dependence of the viscosity is neglected most of the time. In this study we use a self-consistent convection model which includes a grain size- dependent rheology based on the approach by Rozel et al. (2011) and Rozel (2012). Further, we consider a primordial layer and a time-dependent basalt production at the surface to dynamically form the present-day chemical heterogeneities, similar to earlier studies, e.g by Nakagawa & Tackley (2014). With this model we perform a parameter study which includes different densities and viscosities of the imposed primordial layer. We detect possible thermochemical piles based on different criterions, compute their average effective viscosity, density, rheology and grain size and investigate which detecting criterion yields the most realistic results. Our preliminary results show that a higher density and/or viscosity of the piles is needed to keep them at the core-mantle boundary (CMB). Relatively to the ambient mantle grain size is high in the piles but due to the temperature at the CMB the viscosity is not remarkably different than the one of ordinary plumes. We observe that grain size is lower if the density of the LLSVP is lower than the one of our MORB material. In that case the average temperature of the LLSVP is also reduced. Interestingly, changing the reference viscosity is responsible for a change in the average viscosity of the LLSVP but not for a different average grain size. Finally, we compare the numerical results with seismological observations by computing 1D seismic velocity profiles (p-wave, shear-wave and bulk velocities) inside and outside our detected piles using thermodynamic data calculated from Perple_X .

Composition of the low seismic velocity E' layer at the top of Earth's core

NASA Astrophysics Data System (ADS)

Badro, J.; Brodholt, J. P.

2017-12-01

Evidence for a layer (E') at the top of the outer core has been available since the '90s and while different studies suggest slightly different velocity contrasts and thicknesses, the common observation is that the layer has lower velocities than the bulk outer core (PREM). Although there are no direct measurements on the density of this layer, dynamic stability requires it to be less dense than the bulk outer core under those same pressure and temperature conditions. Using ab initio simulations on Fe-Ni-S-C-O-Si liquids we constrain the origin and composition of the low-velocity layer E' at the top of Earth's outer core. We find that increasing the concentration of any light-element always increases velocity and so a low-velocity and low-density layer (for stability) cannot be made by simply increasing light element concentration. This rules out barodiffusion or upwards sedimentation of a light phase for its origin. However, exchanging elements can—depending on the elements exchanged—produce such a layer. We evaluate three possibilities. Firstly, crystallization of a light phase from a core containing more than one light element may make such a layer, but only if the crystalizing phase is very Fe-rich, which is at odds with available phase diagrams at CMB conditions. Secondly, the E' layer may result from incomplete mixing of an early Earth core with a late impactor, depending on the light element compositions of the impactor and Earth's core, but such a primordial stratification is neither supported by dynamical models of the core nor thermodynamic models of core merger after the giant impact. The last and most plausible scenario is core-mantle chemical interaction; using thermodynamic models for metal-silicate partitioning of silicon and oxygen at CMB conditions, we show that a reaction between the core and an FeO-rich basal magma ocean can enrich the core in oxygen while depleting it in silicon, in relative amounts that produce a light and slow layer consistent with seismological observations.

Retinal Connectomics: Towards Complete, Accurate Networks

PubMed Central

Marc, Robert E.; Jones, Bryan W.; Watt, Carl B.; Anderson, James R.; Sigulinsky, Crystal; Lauritzen, Scott

2013-01-01

Connectomics is a strategy for mapping complex neural networks based on high-speed automated electron optical imaging, computational assembly of neural data volumes, web-based navigational tools to explore 1012–1015 byte (terabyte to petabyte) image volumes, and annotation and markup tools to convert images into rich networks with cellular metadata. These collections of network data and associated metadata, analyzed using tools from graph theory and classification theory, can be merged with classical systems theory, giving a more completely parameterized view of how biologic information processing systems are implemented in retina and brain. Networks have two separable features: topology and connection attributes. The first findings from connectomics strongly validate the idea that the topologies complete retinal networks are far more complex than the simple schematics that emerged from classical anatomy. In particular, connectomics has permitted an aggressive refactoring of the retinal inner plexiform layer, demonstrating that network function cannot be simply inferred from stratification; exposing the complex geometric rules for inserting different cells into a shared network; revealing unexpected bidirectional signaling pathways between mammalian rod and cone systems; documenting selective feedforward systems, novel candidate signaling architectures, new coupling motifs, and the highly complex architecture of the mammalian AII amacrine cell. This is but the beginning, as the underlying principles of connectomics are readily transferrable to non-neural cell complexes and provide new contexts for assessing intercellular communication. PMID:24016532

Transgenic mice expressing cyan fluorescent protein as a reporter strain to detect the effects of rotenone toxicity on retinal ganglion cells.

PubMed

Hayworth, C R; Rojas, J C; Gonzalez-Lima, F

2008-01-01

This is the first study using a reporter transgenic model to investigate the effects of an environmental toxin on the retina. Rotenone is a widely used pesticide that inhibits mitochondrial complex I and produces neurotoxicity. Previous studies demonstrated the time course and dose response of rotenone toxicity on retinal ganglion cells (RGC). However, previous analyses of rotenone-induced retinotoxicity provided little detail of the optic nerve axons and cellular pathology. These limitations were successfully surmounted by using a transgenic mouse line shown to express cyan fluorescent protein (CFP) in neurons, including RGC, under regulatory elements of the human the thy1.1 promoter (thy-CFP). Data showed that CFP expression is limited to RGC and their processes in the retina of thy-CFP mice. Eyes exposed to the pesticide rotenone displayed marked alterations in RGC morphology, inner plexiform layer, optic disc, and optic nerves. After 24 h, the number of CFP-labeled RGC was reduced 50%. Correlated with a loss of RGC bodies was an approximate 50% reduction in CFP fluorescence intensity at the optic disc. The findings showed that rotenone-induced degeneration of RGC and their processes can be visualized with exquisite detail in thy-CFP mice, and that this approach may provide a novel and effective way to monitor the association between environmental toxins and neurodegeneration in living animals.

Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa.

PubMed

Beltran, William A; Cideciyan, Artur V; Lewin, Alfred S; Iwabe, Simone; Khanna, Hemant; Sumaroka, Alexander; Chiodo, Vince A; Fajardo, Diego S; Román, Alejandro J; Deng, Wen-Tao; Swider, Malgorzata; Alemán, Tomas S; Boye, Sanford L; Genini, Sem; Swaroop, Anand; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

2012-02-07

Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment.

Diversity and wiring variability of visual local neurons in the Drosophila medulla M6 stratum

PubMed Central

Chin, An-Lun; Lin, Chih-Yung; Fu, Tsai-Feng; Dickson, Barry J; Chiang, Ann-Shyn

2014-01-01

Local neurons in the vertebrate retina are instrumental in transforming visual inputs to extract contrast, motion, and color information and in shaping bipolar-to-ganglion cell transmission to the brain. In Drosophila, UV vision is represented by R7 inner photoreceptor neurons that project to the medulla M6 stratum, with relatively little known of this downstream substrate. Here, using R7 terminals as references, we generated a 3D volume model of the M6 stratum, which revealed a retinotopic map for UV representations. Using this volume model as a common 3D framework, we compiled and analyzed the spatial distributions of more than 200 single M6-specific local neurons (M6-LNs). Based on the segregation of putative dendrites and axons, these local neurons were classified into two families, directional and nondirectional. Neurotransmitter immunostaining suggested a signal routing model in which some visual information is relayed by directional M6-LNs from the anterior to the posterior M6 and all visual information is inhibited by a diverse population of nondirectional M6-LNs covering the entire M6 stratum. Our findings suggest that the Drosophila medulla M6 stratum contains diverse LNs that form repeating functional modules similar to those found in the vertebrate inner plexiform layer. J. Comp. Neurol. 522:3795–3816, 2014. © 2014 Wiley Periodicals, Inc. PMID:24782245

Tracing Primordial Protein Evolution through Structurally Guided Stepwise Segment Elongation*

PubMed Central

Watanabe, Hideki; Yamasaki, Kazuhiko; Honda, Shinya

2014-01-01

The understanding of how primordial proteins emerged has been a fundamental and longstanding issue in biology and biochemistry. For a better understanding of primordial protein evolution, we synthesized an artificial protein on the basis of an evolutionary hypothesis, segment-based elongation starting from an autonomously foldable short peptide. A 10-residue protein, chignolin, the smallest foldable polypeptide ever reported, was used as a structural support to facilitate higher structural organization and gain-of-function in the development of an artificial protein. Repetitive cycles of segment elongation and subsequent phage display selection successfully produced a 25-residue protein, termed AF.2A1, with nanomolar affinity against the Fc region of immunoglobulin G. AF.2A1 shows exquisite molecular recognition ability such that it can distinguish conformational differences of the same molecule. The structure determined by NMR measurements demonstrated that AF.2A1 forms a globular protein-like conformation with the chignolin-derived β-hairpin and a tryptophan-mediated hydrophobic core. Using sequence analysis and a mutation study, we discovered that the structural organization and gain-of-function emerged from the vicinity of the chignolin segment, revealing that the structural support served as the core in both structural and functional development. Here, we propose an evolutionary model for primordial proteins in which a foldable segment serves as the evolving core to facilitate structural and functional evolution. This study provides insights into primordial protein evolution and also presents a novel methodology for designing small sized proteins useful for industrial and pharmaceutical applications. PMID:24356963

RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans.

PubMed

Shamseldin, Hanan; Alazami, Anas M; Manning, Melanie; Hashem, Amal; Caluseiu, Oana; Tabarki, Brahim; Esplin, Edward; Schelley, Susan; Innes, A Micheil; Parboosingh, Jillian S; Lamont, Ryan; Majewski, Jacek; Bernier, Francois P; Alkuraya, Fowzan S

2015-12-03

Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963(∗)] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A HYPOTHESIS FOR THE COLOR BIMODALITY OF JUPITER TROJANS

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

Wong, Ian; Brown, Michael E., E-mail: iwong@caltech.edu

One of the most enigmatic and hitherto unexplained properties of Jupiter Trojans is their bimodal color distribution. This bimodality is indicative of two sub-populations within the Trojans, which have distinct size distributions. In this paper, we present a simple, plausible hypothesis for the origin and evolution of the two Trojan color sub-populations. In the framework of dynamical instability models of early solar system evolution, which suggest a common primordial progenitor population for both Trojans and Kuiper Belt objects, we use observational constraints to assert that the color bimodalities evident in both minor body populations developed within the primordial population priormore » to the onset of instability. We show that, beginning with an initial composition of rock and ices, location-dependent volatile loss through sublimation in this primordial population could have led to sharp changes in the surface composition with heliocentric distance. We propose that the depletion or retention of H{sub 2}S ice on the surface of these objects was the key factor in creating an initial color bimodality. Objects that retained H{sub 2}S on their surfaces developed characteristically redder colors upon irradiation than those that did not. After the bodies from the primordial population were scattered and emplaced into their current positions, they preserved this primordial color bimodality to the present day. We explore predictions of the volatile loss model—in particular, the effect of collisions within the Trojan population on the size distributions of the two sub-populations—and propose further experimental and observational tests of our hypothesis.« less

The subdiaphragmatic part of the phrenic nerve - morphometry and connections to autonomic ganglia.

PubMed

Loukas, Marios; Du Plessis, Maira; Louis, Robert G; Tubbs, R Shane; Wartmann, Christopher T; Apaydin, Nihal

2016-01-01

Few anatomical textbooks offer much information concerning the anatomy and distribution of the phrenic nerve inferior to the diaphragm. The aim of this study was to identify the subdiaphragmatic distribution of the phrenic nerve, the presence of phrenic ganglia, and possible connections to the celiac plexus. One hundred and thirty formalin-fixed adult cadavers were studied. The right phrenic nerve was found inferior to the diaphragm in 98% with 49.1% displaying a right phrenic ganglion. In 22.8% there was an additional smaller ganglion (right accessory phrenic ganglion). The remaining 50.9% had no grossly identifiable right phrenic ganglion. Most (65.5% of specimens) exhibited plexiform communications with the celiac ganglion, aorticorenal ganglion, and suprarenal gland. The left phrenic nerve inferior to the diaphragm was observed in 60% of specimens with 19% containing a left phrenic ganglion. No accessory left phrenic ganglia were observed. The left phrenic ganglion exhibited plexiform communications to several ganglia in 71.4% of specimens. Histologically, the right phrenic and left phrenic ganglia contained large soma concentrated in their peripheries. Both phrenic nerves and ganglia were closely related to the diaphragmatic crura. Surgically, sutures to approximate the crura for repair of hiatal hernias must be placed above the ganglia in order to avoid iatrogenic injuries to the autonomic supply to the diaphragm and abdomen. These findings could also provide a better understanding of the anatomy and distribution of the fibers of that autonomic supply. © 2015 Wiley Periodicals, Inc.

Imatinib mesylate (Glivec) inhibits Schwann cell viability and reduces the size of human plexiform neurofibroma in a xenograft model.

PubMed

Demestre, Maria; Herzberg, Jan; Holtkamp, Nikola; Hagel, Christian; Reuss, David; Friedrich, Reinhard E; Kluwe, Lan; Von Deimling, Andreas; Mautner, Victor-F; Kurtz, Andreas

2010-05-01

Plexiform neurofibromas (PNF), one of the major features of neurofibromatosis type 1 (NF1), are characterized by complex cellular composition and mostly slow but variable growth patterns. In this study, we examined the effect of imatinib mesylate, a receptor tyrosine kinase inhibitor, on PNF-derived Schwann cells and PNF tumour growth in vitro and in vivo. In vitro, PNF-derived primary Schwann cells express platelet-derived growth factors receptors (PDGFR) alpha and beta, both targets of imatinib, and cell viability was reduced by imatinib mesylate, with 50% inhibition concentration (IC(50)) of 10 microM. For in vivo studies, PNF tumour fragments xenografted onto the sciatic nerve of athymic nude mice were first characterized. The tumours persisted for at least 63 days and maintained typical characteristics of PNFs such as complex cellular composition, low proliferation rate and angiogenesis. A transient enlargement of the graft size was due to inflammation by host cells. Treatment with imatinib mesylate at a daily dose of 75 mg/kg for 4 weeks reduced the graft size by an average of 80% (n = 8), significantly different from the original sizes within the group and from sizes of the grafts in 11 untreated mice in the control group (P < 0.001). We demonstrated that grafting human PNF tumour fragments into nude mice provides an adequate in vivo model for drug testing. Our results provide in vivo and in vitro evidence for efficacy of imatinib mesylate for PNF.

Primordial standing waves

NASA Astrophysics Data System (ADS)

Gubitosi, Giulia; Magueijo, João

2018-03-01

We consider the possibility that the primordial fluctuations (scalar and tensor) might have been standing waves at their moment of creation, whether or not they had a quantum origin. We lay down the general conditions for spatial translational invariance, and isolate the pieces of the most general such theory that comply with, or break translational symmetry. We find that, in order to characterize statistically translationally invariant standing waves, it is essential to consider the correlator ⟨c0(k )c0(k')⟩ in addition to the better known ⟨c0(k )c0†(k')⟩ [where c0(k ) are the complex amplitudes of traveling waves]. We then examine how the standard process of "squeezing" (responsible for converting traveling waves into standing waves while the fluctuations are outside the horizon) reacts to being fed primordial standing waves. For translationally invariant systems only one type of standing wave, with the correct temporal phase (the "sine wave"), survives squeezing. Primordial standing waves might therefore be invisible at late times—or not—depending on their phase. Theories with modified dispersion relations behave differently in this respect, since only standing waves with the opposite temporal phase survive at late times.

Primordial nucleosynthesis

PubMed Central

Schramm, David N.

1998-01-01

With the advent of the new extragalactic deuterium observations, Big Bang nucleosynthesis (BBN) is on the verge of undergoing a transformation. In the past, the emphasis has been on demonstrating the concordance of the BBN model with the abundances of the light isotopes extrapolated back to their primordial values by using stellar and galactic evolution theories. As a direct measure of primordial deuterium is converged upon, the nature of the field will shift to using the much more precise primordial D/H to constrain the more flexible stellar and galactic evolution models (although the question of potential systematic error in 4He abundance determinations remains open). The remarkable success of the theory to date in establishing the concordance has led to the very robust conclusion of BBN regarding the baryon density. This robustness remains even through major model variations such as an assumed first-order quark-hadron phase transition. The BBN constraints on the cosmological baryon density are reviewed and demonstrate that the bulk of the baryons are dark and also that the bulk of the matter in the universe is nonbaryonic. Comparison of baryonic density arguments from Lyman-α clouds, x-ray gas in clusters, and the microwave anisotropy are made. PMID:9419322

Primordial nucleosynthesis.

PubMed

Schramm, D N

1998-01-06

With the advent of the new extragalactic deuterium observations, Big Bang nucleosynthesis (BBN) is on the verge of undergoing a transformation. In the past, the emphasis has been on demonstrating the concordance of the BBN model with the abundances of the light isotopes extrapolated back to their primordial values by using stellar and galactic evolution theories. As a direct measure of primordial deuterium is converged upon, the nature of the field will shift to using the much more precise primordial D/H to constrain the more flexible stellar and galactic evolution models (although the question of potential systematic error in 4He abundance determinations remains open). The remarkable success of the theory to date in establishing the concordance has led to the very robust conclusion of BBN regarding the baryon density. This robustness remains even through major model variations such as an assumed first-order quark-hadron phase transition. The BBN constraints on the cosmological baryon density are reviewed and demonstrate that the bulk of the baryons are dark and also that the bulk of the matter in the universe is nonbaryonic. Comparison of baryonic density arguments from Lyman-alpha clouds, x-ray gas in clusters, and the microwave anisotropy are made.

A neural-network based estimator to search for primordial non-Gaussianity in Planck CMB maps

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

Novaes, C.P.; Bernui, A.; Ferreira, I.S.

2015-09-01

We present an upgraded combined estimator, based on Minkowski Functionals and Neural Networks, with excellent performance in detecting primordial non-Gaussianity in simulated maps that also contain a weighted mixture of Galactic contaminations, besides real pixel's noise from Planck cosmic microwave background radiation data. We rigorously test the efficiency of our estimator considering several plausible scenarios for residual non-Gaussianities in the foreground-cleaned Planck maps, with the intuition to optimize the training procedure of the Neural Network to discriminate between contaminations with primordial and secondary non-Gaussian signatures. We look for constraints of primordial local non-Gaussianity at large angular scales in the foreground-cleanedmore » Planck maps. For the SMICA map we found f{sub NL} = 33 ± 23, at 1σ confidence level, in excellent agreement with the WMAP-9yr and Planck results. In addition, for the other three Planck maps we obtain similar constraints with values in the interval f{sub NL}  element of  [33, 41], concomitant with the fact that these maps manifest distinct features in reported analyses, like having different pixel's noise intensities.« less

Primordial non-Gaussianity and power asymmetry with quantum gravitational effects in loop quantum cosmology

NASA Astrophysics Data System (ADS)

Zhu, Tao; Wang, Anzhong; Kirsten, Klaus; Cleaver, Gerald; Sheng, Qin

2018-02-01

Loop quantum cosmology provides a resolution of the classical big bang singularity in the deep Planck era. The evolution, prior to the usual slow-roll inflation, naturally generates excited states at the onset of the slow-roll inflation. It is expected that these quantum gravitational effects could leave its fingerprints on the primordial perturbation spectrum and non-Gaussianity, and lead to some observational evidences in the cosmic microwave background. While the impact of the quantum effects on the primordial perturbation spectrum has been already studied and constrained by current data, in this paper we continue to study such effects but now on the non-Gaussianity of the primordial curvature perturbations. We present detailed and analytical calculations of the non-Gaussianity and show explicitly that the corrections due to the quantum effects are at the same magnitude of the slow-roll parameters in the observable scales and thus are well within current observational constraints. Despite this, we show that the non-Gaussianity in the squeezed limit can be enhanced at superhorizon scales and it is these effects that can yield a large statistical anisotropy on the power spectrum through the Erickcek-Kamionkowski-Carroll mechanism.

Medical management of moyamoya disease and recurrent stroke in an infant with Majewski osteodysplastic primordial dwarfism type II (MOPD II).

PubMed

Kılıç, Esra; Utine, Eda; Unal, Sule; Haliloğlu, Göknur; Oğuz, Kader Karli; Cetin, Mualla; Boduroğlu, Koray; Alanay, Yasemin

2012-10-01

We report an infant diagnosed with Majewski osteodysplastic primordial dwarfism type II at age 8 months, who experienced cerebrovascular morbidities related to this entity. Molecular analysis identified c.2609+1 G>A, intron 14, homozygous splice site mutation in the pericentrin gene. At age 18 months, she developed recurrent strokes and hemiparesis. Brain magnetic resonance imaging and magnetic resonance angiography showed abnormal gyral pattern, cortical acute infarcts, bilateral stenosis of the internal carotid arteries and reduced flow on the cerebral arteries, consistent with moyamoya disease. In Majewski osteodysplastic primordial dwarfism type II, life expectancy is reduced because of high risk of stroke secondary to cerebral vascular anomalies (aneurysms, moyamoya disease). Periodic screening for vascular events is recommended in individuals with Majewski osteodysplastic primordial dwarfism type II every 12-18 months following diagnosis. Our patient was medically managed with low molecular weight heparin followed with aspirin prophylaxis, in addition to carbamazepine and physical rehabilitation. We report an infant with moyamoya disease and recurrent stroke presenting 10 months after diagnosis (at age 18 months), and discuss the outcome of nonsurgical medical management. The presented case is the second youngest case developing stroke and moyamoya disease.

Are cometary nuclei primordial rubble piles?

NASA Technical Reports Server (NTRS)

Weissman, P. R.

1986-01-01

Whipple's icy conglomerate model for the cometary nucleus has had considerable sucess in explaining a variety of cometary phenomena such as gas production rates and nongravitational forces. However, as discussed here, both observational evidence and theoretical considerations suggest that the cometary nucleus may not be a well-consolidated single body, but may instead be a loosely bound agglomeration of smaller fragments, weakly bonded and subject to occasional or even frequent disruptive events. The proposed model is analogous to the 'rubble pile' model suggested for the larger main-belt asteroids, although the larger cometary fragments are expected to be primordial condensations rather than collisionally derived debris as in the asteroid case. The concept of cometary nuclei as primordial rubble piles is proposed as a modification of the basic Whipple model, not as a replacement for it.

Microcephalic Osteodysplastic Primordial Dwarfism, Type II: a Clinical Review.

PubMed

Bober, Michael B; Jackson, Andrew P

2017-04-01

This review will provide an overview of the microcephalic primordial dwarfism (MPD) class of disorders and provide the reader comprehensive clinical review with suggested care guidelines for patients with microcephalic osteodysplastic primordial dwarfism, type II (MOPDII). Over the last 15 years, significant strides have been made in the diagnosis, natural history, and management of MOPDII. MOPDII is the most common and well described form of MPD. The classic features of the MPD group are severe pre- and postnatal growth retardation, with marked microcephaly. In addition to these features, individuals with MOPDII have characteristic facies, skeletal dysplasia, abnormal dentition, and an increased risk for cerebrovascular disease and insulin resistance. Biallelic loss-of-function mutations in the pericentrin gene cause MOPDII, which is inherited in an autosomal recessive manner.

Influence of optic disc size on the diagnostic performance of macular ganglion cell complex and peripapillary retinal nerve fiber layer analyses in glaucoma.

PubMed

Cordeiro, Daniela Valença; Lima, Verônica Castro; Castro, Dinorah P; Castro, Leonardo C; Pacheco, Maria Angélica; Lee, Jae Min; Dimantas, Marcelo I; Prata, Tiago Santos

2011-01-01

To evaluate the influence of optic disc size on the diagnostic accuracy of macular ganglion cell complex (GCC) and conventional peripapillary retinal nerve fiber layer (pRNFL) analyses provided by spectral domain optical coherence tomography (SD-OCT) in glaucoma. Eighty-two glaucoma patients and 30 healthy subjects were included. All patients underwent GCC (7 × 7 mm macular grid, consisting of RNFL, ganglion cell and inner plexiform layers) and pRNFL thickness measurement (3.45 mm circular scan) by SD-OCT. One eye was randomly selected for analysis. Initially, receiver operating characteristic (ROC) curves were generated for different GCC and pRNFL parameters. The effect of disc area on the diagnostic accuracy of these parameters was evaluated using a logistic ROC regression model. Subsequently, 1.5, 2.0, and 2.5 mm(2) disc sizes were arbitrarily chosen (based on data distribution) and the predicted areas under the ROC curves (AUCs) and sensitivities were compared at fixed specificities for each. Average mean deviation index for glaucomatous eyes was -5.3 ± 5.2 dB. Similar AUCs were found for the best pRNFL (average thickness = 0.872) and GCC parameters (average thickness = 0.824; P = 0.19). The coefficient representing disc area in the ROC regression model was not statistically significant for average pRNFL thickness (-0.176) or average GCC thickness (0.088; P ≥ 0.56). AUCs for fixed disc areas (1.5, 2.0, and 2.5 mm(2)) were 0.904, 0.891, and 0.875 for average pRNFL thickness and 0.834, 0.842, and 0.851 for average GCC thickness, respectively. The highest sensitivities - at 80% specificity for average pRNFL (84.5%) and GCC thicknesses (74.5%) - were found with disc sizes fixed at 1.5 mm(2) and 2.5 mm(2). Diagnostic accuracy was similar between pRNFL and GCC thickness parameters. Although not statistically significant, there was a trend for a better diagnostic accuracy of pRNFL thickness measurement in cases of smaller discs. For GCC analysis, an inverse effect was observed.

The primate fovea: Structure, function and development.

PubMed

Bringmann, Andreas; Syrbe, Steffen; Görner, Katja; Kacza, Johannes; Francke, Mike; Wiedemann, Peter; Reichenbach, Andreas

2018-03-30

A fovea is a pitted invagination in the inner retinal tissue (fovea interna) that overlies an area of photoreceptors specialized for high acuity vision (fovea externa). Although the shape of the vertebrate fovea varies considerably among the species, there are two basic types. The retina of many predatory fish, reptilians, and birds possess one (or two) convexiclivate fovea(s), while the retina of higher primates contains a concaviclivate fovea. By refraction of the incoming light, the convexiclivate fovea may function as image enlarger, focus indicator, and movement detector. By centrifugal displacement of the inner retinal layers, which increases the transparency of the central foveal tissue (the foveola), the primate fovea interna improves the quality of the image received by the central photoreceptors. In this review, we summarize ‒ with the focus on Müller cells of the human and macaque fovea ‒ data regarding the structure of the primate fovea, discuss various aspects of the optical function of the fovea, and propose a model of foveal development. The "Müller cell cone" of the foveola comprises specialized Müller cells which do not support neuronal activity but may serve optical and structural functions. In addition to the "Müller cell cone", structural stabilization of the foveal morphology may be provided by the 'z-shaped' Müller cells of the fovea walls, via exerting tractional forces onto Henle fibers. The spatial distribution of glial fibrillary acidic protein may suggest that the foveola and the Henle fiber layer are subjects to mechanical stress. During development, the foveal pit is proposed to be formed by a vertical contraction of the centralmost Müller cells. After widening of the foveal pit likely mediated by retracting astrocytes, Henle fibers are formed by horizontal contraction of Müller cell processes in the outer plexiform layer and the centripetal displacement of photoreceptors. A better understanding of the molecular, cellular, and mechanical factors involved in the developmental morphogenesis and the structural stabilization of the fovea may help to explain the (patho-) genesis of foveal hypoplasia and macular holes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Revisiting Black Holes as Dark Matter

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2017-02-01

Could dark matter be made of intermediate-mass black holes formed in the beginning of the universe? A recent study takes a renewed look at this question.Galactic LurkersThe nature of dark matter has long been questioned, but the recent discovery of gravitational waves by the Laser Interferometer Gravitational-Wave Observatory (LIGO) has renewed interest in the possibility that dark matter could consist of primordial black holes in the mass range of 101000 solar masses.The relative amounts of the different constituents of the universe. Dark matter makes up roughly 27%. [ESA/Planck]According to this model, the extreme density of matter present during the universes early expansion led to the formation of a large number of intermediate-mass black holes. These black holes now hide in the halos of galaxies, constituting the mass that weve measured dynamically but remains unseen.LIGOs first gravitational-wave detection revealed the merger of two black holes that were both tens of solar masses in size. If primordial black holes are indeed a major constituent of dark matter, then LIGOs detection is consistent with what we would expect to find: occasional mergers of the intermediate-mass black holes that formed in the early universe and now lurk in galactic halos.Quasar MicrolensingTheres a catch, however. If there truly were a large number of intermediate-mass primordial black holes hiding in galactic halos, they wouldnt go completely unnoticed: we would see signs of their presence in the gravitational microlensing of background quasars. Unseen primordial black holes in a foreground galaxy could cause an image of a background quasar to briefly brighten which would provide us with clear evidence of such black holes despite our not being able to detect them directly.A depiction of quasar microlensing (click for a closer look!). The microlensing object in the foreground galaxy could be a star (as depicted), a primordial black hole, or any other compact object. [NASA/Jason Cowan (Astronomy Technology Center)]A team of scientists led by Evencio Mediavilla (Institute of Astrophysics of the Canaries, University of La Laguna) has now used our observations of quasar microlensing to place constraints on the amount of dark matter that could be made up of intermediate-mass primordial black holes.Poor Outlook for Primordial Black HolesMediavilla and collaborators used simulations to estimate the effects of a distribution of masses on light from distant quasars, and they then compared their results to microlensing magnification measurements from 24 gravitationally lensed quasars. In this way, they were able to determine both the abundance and masses of possible objects causing the quasar microlensing effects we see.The authors find that the observations constrain the mass of the possible microlensing objects to be between 0.05 and 0.45 solar masses not at all the intermediate-mass black holes postulated. Whats more, they find that the lensing objects make up 20% of the total matter, which is barely more than expected for normal stellar matter. This suggests that normal stars are doing the majority of the quasar microlensing, not a large population of intermediate-mass black holes.What does this mean for primordial black holes as dark matter? Black holes in the range of 10200 stellar masses are unlikely to account for much (if any) dark matter, Mediavilla and collaborators conclude which means that LIGOs detection of gravitational waves likely came from two black holes collapsed from stars, not primordial black holes.CitationE. Mediavilla et al 2017 ApJL 836 L18. doi:10.3847/2041-8213/aa5dab

Immortalization of canine adipose-derived mesenchymal stem cells and their seminiferous tubule transplantation.

PubMed

Fang, Jia; Wei, Yudong; Teng, Xin; Zhao, Shanting; Hua, Jinlian

2018-04-01

Adipose-derived mesenchymal stem cells (ADSCs) are proven to provide good effects in numerous tissue engineering application and other cell-based therapies. However, the difficulty in the proliferation of ADSCs, known as the "Hayflick limit" in vitro, limits their clinical application. Here, we immortalized canine ADSCs (cADSCs) with SV40 gene and transplanted them into busulfan-induced seminiferous tubules of infertile mice. The proliferation of these immortalized cells was improved significantly. Then, cellular differentiation assays showed that the immortalized cADSCs could differentiate into three-germ-layer cells, osteogenesis, chondrogenesis, adipogenesis phenotypes, and primordial germ cell-like cells (PGCLCs). In addition, the immortalized cADSCs can proliferate in the busulfan-induced seminiferous tubules of infertile mice. These findings confirmed that the immortalized cADSCs maintain the criteria of cADSCs. © 2017 Wiley Periodicals, Inc.

The Moon is a Planet Too: Lunar Science and Robotic Exploration

NASA Technical Reports Server (NTRS)

Cohen, Barbara A.

2009-01-01

This slide presentation reviews some of what is known about the moon, and draws parallels between the moon and any other terrestrial planet. The Moon is a cornerstone for all rocky planets The Moon is a terrestrial body, formed and evolved similarly to Earth, Mars, Mercury, Venus, and large asteroids The Moon is a differentiated body, with a layered internal structure (crust, mantle, and core) The Moon is a cratered body, preserving a record of bombardment history in the inner solar system The Moon is an active body, experiencing moonquakes, releasing primordial heat, conducting electricity, sustaining bombardment, and trapping volatile molecules Lunar robotic missions provide early science return to obtain important science and engineering objectives, rebuild a lunar science community, and keep our eyes on the Moon. These lunar missions, both past and future are reviewed.

Progress of the Study of Neutron Interactions with 7Be

NASA Astrophysics Data System (ADS)

Kading, Emily E.; Gai, Moshe; Seiffert, Christoph; Stora, Thierry; Halfon, Shlomi; Paul, Michael; US-Israel-Switzerland Collaboration

2014-09-01

Big Bang Nucleosynthesis (BBN) is today a parameter-free theory. It correctly predicts the abundance relative to hydrogen, of primordial deuterium, helium, and helion but over predicts the relative abundance of primordial 7Li which is primarily (95%) the byproduct of the decay of 7Be. This has been dubbed as the primordial 7Li problem. We are proposing to study the interaction of neutrons with 7Be in order to understand the direct destruction of the primordial 7Be. The experiment being proposed will be performed at the SARAF facility in Israel using the LiLiT neutron generator and an implanted 7Be target produced at ISOLDE from a 7Be sample produced at the PSI. An implantation set up was constructed and tested at ISOLDE using 35 keV 10B. The implanted 10B targets were tested using the intense CERN Pu-Be source. For the first generation measurement of the 7Be(n, α) reaction we plan to use CR-39 plastic track detectors to detect the emanating alpha-particles (and protons). Such detectors were tested in our lab using alpha-source and we are developing the use of these detectors for our measurement. Future experiments will utilize a split gas ionization chamber and silicon detectors. We will review the progress of this research project. Big Bang Nucleosynthesis (BBN) is today a parameter-free theory. It correctly predicts the abundance relative to hydrogen, of primordial deuterium, helium, and helion but over predicts the relative abundance of primordial 7Li which is primarily (95%) the byproduct of the decay of 7Be. This has been dubbed as the primordial 7Li problem. We are proposing to study the interaction of neutrons with 7Be in order to understand the direct destruction of the primordial 7Be. The experiment being proposed will be performed at the SARAF facility in Israel using the LiLiT neutron generator and an implanted 7Be target produced at ISOLDE from a 7Be sample produced at the PSI. An implantation set up was constructed and tested at ISOLDE using 35 keV 10B. The implanted 10B targets were tested using the intense CERN Pu-Be source. For the first generation measurement of the 7Be(n, α) reaction we plan to use CR-39 plastic track detectors to detect the emanating alpha-particles (and protons). Such detectors were tested in our lab using alpha-source and we are developing the use of these detectors for our measurement. Future experiments will utilize a split gas ionization chamber and silicon detectors. We will review the progress of this research project. Supported in part by the USDOE Grant Number DE-FG02-94ER40870 and the US-Israel Binational Science Foundation Grant Number 2012098.

Observational constraints on the primordial curvature power spectrum

NASA Astrophysics Data System (ADS)

Emami, Razieh; Smoot, George F.

2018-01-01

CMB temperature fluctuation observations provide a precise measurement of the primordial power spectrum on large scales, corresponding to wavenumbers 10‑3 Mpc‑1 lesssim k lesssim 0.1 Mpc‑1, [1-7, 11]. Luminous red galaxies and galaxy clusters probe the matter power spectrum on overlapping scales (0.02 Mpc‑1 lesssim k lesssim 0.7 Mpc‑1 [10, 12-20]), while the Lyman-alpha forest reaches slightly smaller scales (0.3 Mpc‑1 lesssim k lesssim 3 Mpc‑1 [22]). These observations indicate that the primordial power spectrum is nearly scale-invariant with an amplitude close to 2 × 10‑9, [5, 23-28]. These observations strongly support Inflation and motivate us to obtain observations and constraints reaching to smaller scales on the primordial curvature power spectrum and by implication on Inflation. We are able to obtain limits to much higher values of k lesssim 105 Mpc‑1 and with less sensitivity even higher k lesssim 1019‑ 1023 Mpc‑1 using limits from CMB spectral distortions and other limits on ultracompact minihalo objects (UCMHs) and Primordial Black Holes (PBHs). PBHs are one of the known candidates for the Dark Matter (DM). Due to their very early formation, they could give us valuable information about the primordial curvature perturbations. These are complementary to other cosmological bounds on the amplitude of the primordial fluctuations. In this paper, we revisit and collect all the published constraints on both PBHs and UCMHs. We show that unless one uses the CMB spectral distortion, PBHs give us a very relaxed bounds on the primordial curvature perturbations. UCMHs, on the other hand, are very informative over a reasonable k range (3 lesssim k lesssim 106 Mpc‑1) and lead to significant upper-bounds on the curvature spectrum. We review the conditions under which the tighter constraints on the UCMHs could imply extremely strong bounds on the fraction of DM that could be PBHs in reasonable models. Failure to satisfy these conditions would lead to over production of the UCMHs which is inconsistent with the observations. Therefore, we can almost rule out PBH within their overlap scales with the UCMHs. We compare the UCMH bounds coming from those experiments which are sensitive to the nature of the DM, such as γ-rays, Neutrinos and Reionization, with those which are insensitive to the type of the DM, e.g. the pulsar-timing as well as CMB spectral distortion. We explicitly show that they lead to comparable results which are independent of the type of DM. These bounds however do depend on the required initial density perturbation, i.e. δmin. It could be either a constant or a scale-dependent function. As we will show, the constraints differ by three orders of magnitude depend on our choice of required initial perturbations.

Baryogenesis in extended inflation. 2: Baryogenesis via primordial black holes

NASA Technical Reports Server (NTRS)

Barrow, John D.; Copeland, Edmund J.; Kolb, Edward W.; Liddle, Andrew R.

1990-01-01

Baryogenesis at the end of extended inflation is studied. Extended inflation is brought to an end by the collisions of bubble walls surrounding regions of true vacuum, a process which produces particles well out of thermal equilibrium. The possibility that the wall collisions may provide a significant density of primordial black holes is considered and their possible role in generating a baryon asymmetry is examined.

Primordial large-scale electromagnetic fields from gravitoelectromagnetic inflation

NASA Astrophysics Data System (ADS)

Membiela, Federico Agustín; Bellini, Mauricio

2009-04-01

We investigate the origin and evolution of primordial electric and magnetic fields in the early universe, when the expansion is governed by a cosmological constant Λ0. Using the gravitoelectromagnetic inflationary formalism with A0 = 0, we obtain the power of spectrums for large-scale magnetic fields and the inflaton field fluctuations during inflation. A very important fact is that our formalism is naturally non-conformally invariant.

The Observational Determination of the Primordial Helium Abundance: a Y2K Status Report

NASA Astrophysics Data System (ADS)

Skillman, Evan D.

I review observational progress and assess the current state of the determination of the primordial helium abundance, Yp. At present there are two determinations with non-overlapping errors. My impression is that the errors have been under-estimated in both studies. I review recent work on errors assessment and give suggestions for decreasing systematic errors in future studies.

Giant Impacts and Earth's Primordial Atmosphere

NASA Astrophysics Data System (ADS)

Agnor, C.; Asphaug, E.

2002-09-01

Estimates of Earth's accretion timescale based on modeling (e.g. Wetherill 1990) and isotopic evidence (Halliday and Porcelli 2000) indicate that the Earth formed in 25-100 Myr. At least a portion of this accretion took place in the presence of the solar nebula. While the problem of nailing down the nebular lifetime remains open, observations of dust disks surrounding young stars and meteoritic evidence suggest that the gas disk existed and was involved in making planetary material for 10 Myr (e.g. Podosek & Cassen 1994, Trilling et al. 2001). The persistence of a remnant of the nebula's original gas disk during terrestrial planet accretion is certainly plausible. The existence of this remnant nebula has dynamical (Agnor & Ward 2002, Kominami & Ida 2002) and geochemical (Porcelli & Pepin 2000) implications for terrestrial planet formation. Nakazawa et al. (1985) explored the structure of Earth's primordial atmosphere as the solar nebula was dissipating. They found that even for low surface densities of nebular gas ( σ gas ~ 1 g cm-2 or ~0.1% of the minimum mass nebula), Earth can capture a significant primordial atmosphere directly from the nebula (i.e. total mass up to a few lunar masses, or ~ 105 times the current atmosphere). Such a massive primordial atmosphere may have played a dynamical role in the formation of the Moon (e.g. models of lunar capture have employed aerodynamic drag in Earth's atmosphere as the primary mechanism for reducing the Moon's orbital energy, Nakazawa et al. 1983). Conversely, the formation of the Moon may have played a role in removing Earth's primordial atmosphere. Giant impacts have been suggested as one possible mechanism that could accomplish global atmospheric removal (Ahrens 1993). We are using smooth particle hydrodynamics (SPH) to model the removal of Earth's primordial atmosphere via giant impact. We employ initial conditions similar to recent works on lunar formation (e.g. Canup & Asphaug 2001) but also include ideal gas atmospheres on the colliding bodies. In addition to exploring the hydrodynamics and efficiency of atmospheric removal via giant impact, we also examine the influence of Earth's protoatmosphere on the ejecta velocity distribution and formation of the proto-lunar disk.

The Last Gasp of Gas Giant Planet Formation: A Spitzer Study of the 5 Myr Old Cluster NGC 2362

NASA Astrophysics Data System (ADS)

Currie, Thayne; Lada, Charles J.; Plavchan, Peter; Robitaille, Thomas P.; Irwin, Jonathan; Kenyon, Scott J.

2009-06-01

Expanding upon the Infrared Array Camera (IRAC) survey from Dahm & Hillenbrand, we describe Spitzer IRAC and Multiband Imaging Photometer for Spitzer observations of the populous, 5 Myr old open cluster NGC 2362. We analyze the mid-IR colors of cluster members and compared their spectral energy distributions (SEDs) to star+circumstellar disk models to constrain the disk morphologies and evolutionary states. Early/intermediate-type confirmed/candidate cluster members either have photospheric mid-IR emission or weak, optically thin IR excess emission at λ >= 24 μm consistent with debris disks. Few late-type, solar/subsolar-mass stars have primordial disks. The disk population around late-type stars is dominated by disks with inner holes (canonical "transition disks") and "homologously depleted" disks. Both types of disks represent an intermediate stage between primordial disks and debris disks. Thus, in agreement with previous results, we find that multiple paths for the primordial-to-debris disk transition exist. Because these "evolved primordial disks" greatly outnumber primordial disks, our results undermine standard arguments in favor of a lsim105 yr timescale for the transition based on data from Taurus-Auriga. Because the typical transition timescale is far longer than 105 yr, these data also appear to rule out standard ultraviolet photoevaporation scenarios as the primary mechanism to explain the transition. Combining our data with other Spitzer surveys, we investigate the evolution of debris disks around high/intermediate-mass stars and investigate timescales for giant planet formation. Consistent with Currie et al., the luminosity of 24 μm emission in debris disks due to planet formation peaks at ≈10-20 Myr. If the gas and dust in disks evolve on similar timescales, the formation timescale for gas giant planets surrounding early-type, high/intermediate-mass (gsim1.4 M sun) stars is likely 1-5 Myr. Most solar/subsolar-mass stars detected by Spitzer have SEDs that indicate their disks may be actively leaving the primordial disk phase. Thus, gas giant planet formation may also occur by ~5 Myr around solar/subsolar-mass stars as well.

DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers

PubMed Central

Isagawa, Takayuki; Nagae, Genta; Shiraki, Nobuaki; Fujita, Takanori; Sato, Noriko; Ishikawa, Shumpei; Kume, Shoen; Aburatani, Hiroyuki

2011-01-01

Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes. PMID:22016810

DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.

PubMed

Isagawa, Takayuki; Nagae, Genta; Shiraki, Nobuaki; Fujita, Takanori; Sato, Noriko; Ishikawa, Shumpei; Kume, Shoen; Aburatani, Hiroyuki

2011-01-01

Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes.

Halolike Phenomenon Around a Café au Lait Spot Superimposed on a Mongolian Spot.

PubMed

Neri, Iria; Lambertini, Martina; Tengattini, Vera; Rivalta, Beatrice; Patrizi, Annalisa

2017-05-01

An 8-month-old Caucasian infant with neurofibromatosis type 1 presented with a congenital plexiform neurofibroma and multiple café au lait spots. A pale area surrounded one of the café au lait spots located on the left gluteus in the area of dermal melanocytosis. This halolike phenomenon results from the disappearance of the Mongolian spot around the café au lait spots, revealing normal pigmented skin. This sign has been described rarely in the literature and the pathogenic mechanism is unclear. © 2017 Wiley Periodicals, Inc.

Cell Autonomous Phosphoinositide 3-Kinase Activation in Oocytes Disrupts Normal Ovarian Function Through Promoting Survival and Overgrowth of Ovarian Follicles

PubMed Central

Ebbert, Katherine; Cordeiro, Marilia H.; Romero, Megan; Zhu, Jie; Serna, Vanida Ann; Whelan, Kelly A.; Woodruff, Teresa K.

2015-01-01

In this study, we explored the effects of oocytic phosphoinositide 3-kinase (PI3K) activation on folliculogensis by generating transgenic mice, in which the oocyte-specific Cre-recombinase induces the expression of constitutively active mutant PI3K during the formation of primordial follicles. The ovaries of neonatal transgenic (Cre+) mice showed significantly reduced apoptosis in follicles, which resulted in an excess number of follicles per ovary. Thus, the elevation of phosphatidylinositol (3,4,5)-trisphosphate levels within oocytes promotes the survival of follicles during neonatal development. Despite the increase in AKT phosphorylation, primordial follicles in neonatal Cre+ mice remained dormant demonstrating a nuclear accumulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). These primordial follicles containing a high level of nuclear PTEN persisted in postpubertal females, suggesting that PTEN is the dominant factor in the maintenance of female reproductive lifespan through the regulation of primordial follicle recruitment. Although the oocytic PI3K activity and PTEN levels were elevated, the activation of primordial follicles and the subsequent accumulation of antral follicles with developmentally competent oocytes progressed normally in prepubertal Cre+ mice. However, mature Cre+ female mice were anovulatory. Because postnatal day 50 Cre+ mice released cumulus-oocyte complexes with developmentally competent oocytes in response to super-ovulation treatment, the anovulatory phenotype was not due to follicular defects but rather endocrine abnormalities, which were likely caused by the excess number of overgrown follicles. Our current study has elucidated the critical role of oocytic PI3K activity in follicular function, as well as the presence of a PTEN-mediated mechanism in the prevention of immature follicle activation. PMID:25594701

Primordial binary populations in low-density star clusters as seen by Chandra: globular clusters versus old open clusters

NASA Astrophysics Data System (ADS)

van den Berg, Maureen C.

2015-08-01

The binaries in the core of a star cluster are the energy source that prevents the cluster from experiencing core collapse. To model the dynamical evolution of a cluster, it is important to have constraints on the primordial binary content. X-ray observations of old star clusters are very efficient in detecting the close interacting binaries among the cluster members. The X-ray sources in star clusters are a mix of binaries that were dynamically formed and primordial binaries. In massive, dense star clusters, dynamical encounters play an important role in shaping the properties and numbers of the binaries. In contrast, in the low-density clusters the impact of dynamical encounters is presumed to be very small, and the close binaries detected in X-rays represent a primordial population. The lowest density globular clusters have current masses and central densities similar to those of the oldest open clusters in our Milky Way. I will discuss the results of studies with the Chandra X-ray Observatory that have nevertheless revealed a clear dichotomy: far fewer (if any at all) X-ray sources are detected in the central regions of the low-density globular clusters compared to the number of secure cluster members that have been detected in old open clusters (above a limiting X-ray luminosity of typically 4e30 erg/s). The low stellar encounter rates imply that dynamical destruction of binaries can be ignored at present, therefore an explanation must be sought elsewhere. I will discuss several factors that can shed light on the implied differences between the primordial close binary populations in the two types of star clusters.

S100A8, An Oocyte-Specific Chemokine, Directs the Migration of Ovarian Somatic Cells During Mouse Primordial Follicle Assembly.

PubMed

Teng, Zhen; Wang, Chao; Wang, Yijing; Huang, Kun; Xiang, Xi; Niu, Wanbao; Feng, Lizhao; Zhao, Lihua; Yan, Hao; Zhang, Hua; Xia, Guoliang

2015-12-01

In the mammalian ovaries, the primordial follicle pool determines the reproductive capability over the lifetime of a female. The primordial follicle is composed of two cell members, namely the oocyte and the pre-granulosa cells that encircle the oocyte. However, it is unclear what factors are involved in the reorganization of the two distinct cells into one functional unit. This study was performed to address this issue. Firstly, in an in vitro reconstruction system, dispersed ovarian cells from murine fetal ovaries at 19.0 days post coitum (dpc) reassembled into follicle-like structures, independent of the physical distance between the cells, implying that either oocytes or ovarian somatic cells (OSCs) were motile. We then carried out a series of transwell assay experiments, and determined that it was in fact 19.0 dpc OSCs (as opposed to oocytes), which exhibited a significant chemotactic response to both fetal bovine serum and oocytes themselves. We observed that S100A8, a multi-functional chemokine, may participate in the process as it is mainly expressed in oocytes within the cysts/plasmodia. S100A8 significantly promoted the number of migrating OSCs by 2.5 times in vitro, of which 66.9% were FOXL2 protein-positive cells, implying that the majority of motile OSCs were pre-granulosa cells. In addition, an S100A8-specific antibody inhibited the formation of follicle-like reconstruction cell mass in vitro. And, the primordial follicle formation was reduced when S100a8-specific siRNA was applied onto in vitro cultured 17.5 dpc ovary. Therefore, S100A8 could be a chemokine of oocyte origin, which attracts OSCs to form the primordial follicles. © 2015 Wiley Periodicals, Inc.

AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy.

PubMed

Kano, Motohiro; Sosulski, Amanda E; Zhang, LiHua; Saatcioglu, Hatice D; Wang, Dan; Nagykery, Nicholas; Sabatini, Mary E; Gao, Guangping; Donahoe, Patricia K; Pépin, David

2017-02-28

The ovarian reserve represents the stock of quiescent primordial follicles in the ovary which is gradually depleted during a woman's reproductive lifespan, resulting in menopause. Müllerian inhibiting substance (MIS) (or anti-Müllerian hormone/AMH), which is produced by granulosa cells of growing follicles, has been proposed as a negative regulator of primordial follicle activation. Here we show that long-term parenteral administration of superphysiological doses of MIS, using either an adeno-associated virus serotype 9 (AAV9) gene therapy vector or recombinant protein, resulted in a complete arrest of folliculogenesis in mice. The ovaries of MIS-treated mice were smaller than those in controls and did not contain growing follicles but retained a normal ovarian reserve. When mice treated with AAV9/MIS were paired with male breeders, they exhibited complete and permanent contraception for their entire reproductive lifespan, disrupted vaginal cycling, and hypergonadotropic hypogonadism. However, when ovaries from AAV9-MIS-treated mice were transplanted orthotopically into normal recipient mice, or when treatment with the protein was discontinued, folliculogenesis resumed, suggesting reversibility. One of the important causes of primary ovarian insufficiency is chemotherapy-induced primordial follicle depletion, which has been proposed to be mediated in part by increased activation. To test the hypothesis that MIS could prevent chemotherapy-induced overactivation, mice were given carboplatin, doxorubicin, or cyclophosphamide and were cotreated with AAV9-MIS, recombinant MIS protein, or vehicle controls. We found significantly more primordial follicles in MIS-treated animals than in controls. Thus treatment with MIS may provide a method of contraception with the unique characteristic of blocking primordial follicle activation that could be exploited to prevent the primary ovarian insufficiency often associated with chemotherapy.

AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy

PubMed Central

Kano, Motohiro; Sosulski, Amanda E.; Zhang, LiHua; Saatcioglu, Hatice D.; Wang, Dan; Nagykery, Nicholas; Sabatini, Mary E.; Gao, Guangping; Donahoe, Patricia K.; Pépin, David

2017-01-01

The ovarian reserve represents the stock of quiescent primordial follicles in the ovary which is gradually depleted during a woman’s reproductive lifespan, resulting in menopause. Müllerian inhibiting substance (MIS) (or anti-Müllerian hormone/AMH), which is produced by granulosa cells of growing follicles, has been proposed as a negative regulator of primordial follicle activation. Here we show that long-term parenteral administration of superphysiological doses of MIS, using either an adeno-associated virus serotype 9 (AAV9) gene therapy vector or recombinant protein, resulted in a complete arrest of folliculogenesis in mice. The ovaries of MIS-treated mice were smaller than those in controls and did not contain growing follicles but retained a normal ovarian reserve. When mice treated with AAV9/MIS were paired with male breeders, they exhibited complete and permanent contraception for their entire reproductive lifespan, disrupted vaginal cycling, and hypergonadotropic hypogonadism. However, when ovaries from AAV9-MIS–treated mice were transplanted orthotopically into normal recipient mice, or when treatment with the protein was discontinued, folliculogenesis resumed, suggesting reversibility. One of the important causes of primary ovarian insufficiency is chemotherapy-induced primordial follicle depletion, which has been proposed to be mediated in part by increased activation. To test the hypothesis that MIS could prevent chemotherapy-induced overactivation, mice were given carboplatin, doxorubicin, or cyclophosphamide and were cotreated with AAV9-MIS, recombinant MIS protein, or vehicle controls. We found significantly more primordial follicles in MIS-treated animals than in controls. Thus treatment with MIS may provide a method of contraception with the unique characteristic of blocking primordial follicle activation that could be exploited to prevent the primary ovarian insufficiency often associated with chemotherapy. PMID:28137855

Origin of the lunar highlands Mg-suite: An integrated petrology, geochemistry, chronology, and remote sensing perspective

DOE PAGES

Shearer, C. K.; Elardo, S. M.; Petro, N. E.; ...

2014-12-23

The Mg-suite represents an enigmatic episode of lunar highlands magmatism that presumably represents the first stage of crustal building following primordial differentiation. This review examines the mineralogy, geochemistry, petrology, chronology, and the planetary-scale distribution of this suite of highlands plutonic rocks, presents models for their origin, examines petrogenetic relationships to other highlands rocks, and explores the link between this style of magmatism and early stages of lunar differentiation. Of the models considered for the origin of the parent magmas for the Mg-suite, the data best fit a process in which hot (solidus temperature at ≥2 GPa = 1600 to 1800more » °C) and less dense (r ~3100 kg/m3) early lunar magma ocean cumulates rise to the base of the crust during cumulate pile overturn. Some decompressional melting would occur, but placing a hot cumulate horizon adjacent to the plagioclase-rich primordial crust and KREEP-rich lithologies (at temperatures of <1300 °C) would result in the hybridization of these divergent primordial lithologies, producing Mg-suite parent magmas. As urKREEP (primeval KREEP) is not the “petrologic driver” of this style of magmatism, outside of the Procellarum KREEP Terrane (PKT), Mg-suite magmas are not required to have a KREEP signature. Evaluation of the chronology of this episode of highlands evolution indicates that Mg-suite magmatism was initiated soon after primordial differentiation (<10 m.y.). Alternatively, the thermal event associated with the mantle overturn may have disrupted the chronometers utilized to date the primordial crust. Petrogenetic relationships between the Mg-suite and other highlands suites (e.g., alkali-suite and magnesian anorthositic granulites) are consistent with both fractional crystallization processes and melting of distinctly different hybrid sources.« less

Zearalenone exposure impairs ovarian primordial follicle formation via down-regulation of Lhx8 expression in vitro

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

Zhang, Guo-Liang

Zearalenone (ZEA) is an estrogenic mycotoxin mainly produced as a secondary metabolite by numerous species of Fusarium. Previous work showed that ZEA had a negative impact on domestic animals with regard to reproduction. The adverse effects and the mechanisms of ZEA on mammalian ovarian folliculogenesis remain largely unknown, particularly its effect on primordial follicle formation. Thus, we investigated the biological effects of ZEA exposure on murine ovarian germ cell cyst breakdown and primordial follicle assembly. Our results demonstrated that newborn mouse ovaries exposed to 10 or 30 μM ZEA in vitro had significantly less germ cell numbers compared to themore » control group. Moreover, the presence of ZEA in vitro increased the numbers of TUNEL and γH2AX positive cells within mouse ovaries and the ratio of mRNA levels of the apoptotic genes Bax/Bcl-2. Furthermore, ZEA exposure reduced the mRNA of oocyte specific genes such as LIM homeobox 8 (Lhx8), newborn ovary homeobox (Nobox), spermatogenesis and oogenesis helix-loop-helix (Sohlh2), and factor in the germline alpha (Figlα) in a dose dependent manner. Exposure to ZEA led to remarkable changes in the Lhx8 3′-UTR DNA methylation dynamics in oocytes and severely impaired folliculogenesis in ovaries after transplantation under the kidney capsules of immunodeficient mice. In conclusion, ZEA exposure impairs mouse primordial follicle formation in vitro. - Highlights: • First time to evaluate the impact of ZEA on primordial follicle formation • ZEA exposure increases oocyte apoptosis and delays germ cell cyst breakdown. • ZEA exposure impairs the expression of LHX8 by affecting its DNA methylation.« less

Effects of ordinary and superconducting cosmic strings on primordial nucleosynthesis

NASA Technical Reports Server (NTRS)

Hodges, Hardy M.; Turner, Michael S.

1988-01-01

A precise calculation is done of the primordial nucleosynthesis constraint on the energy per length of ordinary and superconducting cosmic strings. A general formula is provided for the constraint on the string tension for ordinary strings. Using the current values for the various parameters that describe the evolution of loops, the constraint for ordinary strings is G mu less than 2.2 x 10 to the minus 5 power. Our constraint is weaker than previously quoted limits by a factor of approximately 5. For superconducting loops, with currents generated by primordial magnetic fields, the constraint can be less or more stringent than this limit, depending on the strength of the magnetic field. It is also found in this case that there is a negligible amount of entropy production if the electromagnetic radiation from strings thermalizes with the radiation background.

Loop corrections to primordial fluctuations from inflationary phase transitions

NASA Astrophysics Data System (ADS)

Wu, Yi-Peng; Yokoyama, Jun'ichi

2018-05-01

We investigate loop corrections to the primordial fluctuations in the single-field inflationary paradigm from spectator fields that experience a smooth transition of their vacuum expectation values. We show that when the phase transition involves a classical evolution effectively driven by a negative mass term from the potential, important corrections to the curvature perturbation can be generated by field perturbations that are frozen outside the horizon by the time of the phase transition, yet the correction to tensor perturbation is naturally suppressed by the spatial derivative couplings between spectator fields and graviton. At one-loop level, the dominant channel for the production of primordial fluctuations comes from a pair-scattering of free spectator fields that decay into the curvature perturbations, and this decay process is only sensitive to field masses comparable to the Hubble scale of inflation.

Precision measures of the primordial deuterium abundance.

NASA Astrophysics Data System (ADS)

Cooke, R. J.; Pettini, M.; Jorgenson, R. A.; Murphy, M. T.; Steidel, C. C.

Near-pristine damped Lyman-alpha systems (DLAs) are the ideal environments to measure the primordial abundance of deuterium. In this conference report, I summarise our ongoing research programme to obtain the most precise determination of the primordial deuterium abundance from five high redshift DLAs. From this sample, we derive (D/H)_p = (2.53±0.04)×105, corresponding to a baryon density 100 Omega_b ,0 h2 = 2.202±0.046 assuming the standard model of Big Bang Nucleosynthesis. This value is in striking agreement with that measured from the temperature fluctuations imprinted on the cosmic microwave background. Although we find no strong evidence for new physics beyond the standard model, this line of research shows great promise in the near-future, when the next generation 30+ m telescopes equipped with echelle spectrographs come online.

Chiral primordial blue tensor spectra from the axion-gauge couplings

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

Obata, Ippei, E-mail: obata@tap.scphys.kyoto-u.ac.jp

We suggest the new feature of primordial gravitational waves sourced by the axion-gauge couplings, whose forms are motivated by the dimensional reduction of the form field in the string theory. In our inflationary model, as an inflaton we adopt two types of axion, dubbed the model-independent axion and the model-dependent axion, which couple with two gauge groups with different sign combination each other. Due to these forms both polarization modes of gauge fields are amplified and enhance both helicies of tensor modes during inflation. We point out the possibility that a primordial blue-tilted tensor power spectra with small chirality aremore » provided by the combination of these axion-gauge couplings, intriguingly both amplitudes and chirality are potentially testable by future space-based gravitational wave interferometers such as DECIGO and BBO project.« less

The Primordial Entropy of Jupiter

NASA Astrophysics Data System (ADS)

Cumming, Andrew; Helled, Ravit; Venturini, Julia

2018-04-01

The formation history of giant planets determines their primordial structure and consequent evolution. We simulate various formation paths of Jupiter to determine its primordial entropy, and find that a common outcome is for proto-Jupiter to have non-convective regions in its interior. We use planet formation models to calculate how the entropy and post-formation luminosity depend on model properties such as the solid accretion rate and opacity, and show that the gas accretion rate and its time evolution play a key role in determining the entropy profile. The predicted luminosity of Jupiter shortly after formation varies by a factor of 2-3 for different choices of model parameters. We find that entropy gradients inside Jupiter persist for ˜10 Myr after formation. We suggest that these gradients should be considered together with heavy-element composition gradients when modeling Jupiter's evolution and internal structure.

Primordial soup was edible: abiotically produced Miller-Urey mixture supports bacterial growth.

PubMed

Xie, Xueshu; Backman, Daniel; Lebedev, Albert T; Artaev, Viatcheslav B; Jiang, Liying; Ilag, Leopold L; Zubarev, Roman A

2015-09-28

Sixty years after the seminal Miller-Urey experiment that abiotically produced a mixture of racemized amino acids, we provide a definite proof that this primordial soup, when properly cooked, was edible for primitive organisms. Direct admixture of even small amounts of Miller-Urey mixture strongly inhibits E. coli bacteria growth due to the toxicity of abundant components, such as cyanides. However, these toxic compounds are both volatile and extremely reactive, while bacteria are highly capable of adaptation. Consequently, after bacterial adaptation to a mixture of the two most abundant abiotic amino acids, glycine and racemized alanine, dried and reconstituted MU soup was found to support bacterial growth and even accelerate it compared to a simple mixture of the two amino acids. Therefore, primordial Miller-Urey soup was perfectly suitable as a growth media for early life forms.

The primordial entropy of Jupiter

NASA Astrophysics Data System (ADS)

Cumming, Andrew; Helled, Ravit; Venturini, Julia

2018-07-01

The formation history of giant planets determines their primordial structure and consequent evolution. We simulate various formation paths of Jupiter to determine its primordial entropy, and find that a common outcome is for proto-Jupiter to have non-convective regions in its interior. We use planet formation models to calculate how the entropy and post-formation luminosity depend on model properties such as the solid accretion rate and opacity, and show that the gas accretion rate and its time evolution play a key role in determining the entropy profile. The predicted luminosity of Jupiter shortly after formation varies by a factor of 2-3 for different choices of model parameters. We find that entropy gradients inside Jupiter persist for ˜10 Myr after formation. We suggest that these gradients should be considered together with heavy-element composition gradients when modelling Jupiter's evolution and internal structure.

Mars primordial crust: unique sites for investigating proto-biologic properties.

PubMed

Perry, Randall S; Hartmann, William K

2006-12-01

The Martian meteorite collection suggests that intact outcrops or boulder-scale fragments of the 4.5 Ga Martian crust exist within tens of meters of the present day surface of Mars. Mars may be the only planet where such primordial crust samples, representing the first 100 Ma of a planet's environment, are available. The primordial crust has been destroyed on Earth by plate tectonics and other geological phenomena and is buried on the Moon under hundreds or thousands of meters of megaregoltih. Early Mars appears to have been remarkably similar to early Earth, and samples of rock from the first few Ma or first 100 Ma may reveal "missing link" proto-biological forms that could shed light on the transition from abiotic organic chemistry to living cells. Such organic snapshots of nascent life are unlikely to be found on Earth.

Gravitational waves in cold dark matter

NASA Astrophysics Data System (ADS)

Flauger, Raphael; Weinberg, Steven

2018-06-01

We study the effects of cold dark matter on the propagation of gravitational waves of astrophysical and primordial origin. We show that the dominant effect of cold dark matter on gravitational waves from astrophysical sources is a small frequency dependent modification of the propagation speed of gravitational waves. However, the magnitude of the effect is too small to be detected in the near future. We furthermore show that the spectrum of primordial gravitational waves in principle contains detailed information about the properties of dark matter. However, depending on the wavelength, the effects are either suppressed because the dark matter is highly nonrelativistic or because it contributes a small fraction of the energy density of the universe. As a consequence, the effects of cold dark matter on primordial gravitational waves in practice also appear too small to be detectable.

Cosmological lepton asymmetry, primordial nucleosynthesis and sterile neutrinos

NASA Astrophysics Data System (ADS)

Abazajian, Kevork; Bell, Nicole F.; Fuller, George M.; Wong, Yvonne Y. Y.

2005-09-01

We study post weak decoupling coherent active-sterile and active-active matter-enhanced neutrino flavor transformation in the early Universe. We show that flavor conversion efficiency at Mikheyev-Smirnov-Wolfenstein resonances is likely to be high (adiabatic evolution) for relevant neutrino parameters and energies. However, we point out that these resonances cannot sweep smoothly and continuously with the expansion of the Universe. We show how neutrino flavor conversion in this way can leave both the active and sterile neutrinos with nonthermal energy spectra, and how, in turn, these distorted energy spectra can affect the neutron-to-proton ratio, primordial nucleosynthesis, and cosmological mass/closure constraints on sterile neutrinos. We demonstrate that the existence of a light sterile neutrino which mixes with active neutrinos can change fundamentally the relationship between the cosmological lepton numbers and the primordial nucleosynthesis He4 yield.

Non-local bias in the halo bispectrum with primordial non-Gaussianity

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

Tellarini, Matteo; Ross, Ashley J.; Wands, David

2015-07-01

Primordial non-Gaussianity can lead to a scale-dependent bias in the density of collapsed halos relative to the underlying matter density. The galaxy power spectrum already provides constraints on local-type primordial non-Gaussianity complementary those from the cosmic microwave background (CMB), while the bispectrum contains additional shape information and has the potential to outperform CMB constraints in future. We develop the bias model for the halo density contrast in the presence of local-type primordial non-Gaussianity, deriving a bivariate expansion up to second order in terms of the local linear matter density contrast and the local gravitational potential in Lagrangian coordinates. Nonlinear evolutionmore » of the matter density introduces a non-local tidal term in the halo model. Furthermore, the presence of local-type non-Gaussianity in the Lagrangian frame leads to a novel non-local convective term in the Eulerian frame, that is proportional to the displacement field when going beyond the spherical collapse approximation. We use an extended Press-Schechter approach to evaluate the halo mass function and thus the halo bispectrum. We show that including these non-local terms in the halo bispectra can lead to corrections of up to 25% for some configurations, on large scales or at high redshift.« less

Features in the primordial spectrum from WMAP: A wavelet analysis

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

Shafieloo, Arman; Souradeep, Tarun; Manimaran, P.

2007-06-15

Precise measurements of the anisotropies in the cosmic microwave background enable us to do an accurate study on the form of the primordial power spectrum for a given set of cosmological parameters. In a previous paper [A. Shafieloo and T. Souradeep, Phys. Rev. D 70, 043523 (2004).], we implemented an improved (error sensitive) Richardson-Lucy deconvolution algorithm on the measured angular power spectrum from the first year of WMAP data to determine the primordial power spectrum assuming a concordance cosmological model. This recovered spectrum has a likelihood far better than a scale invariant, or, 'best fit' scale free spectra ({delta}lnL{approx_equal}25 withmore » respect to the Harrison-Zeldovich spectrum, and, {delta}lnL{approx_equal}11 with respect to the power law spectrum with n{sub s}=0.95). In this paper we use the discrete wavelet transform (DWT) to decompose the local features of the recovered spectrum individually to study their effect and significance on the recovered angular power spectrum and hence the likelihood. We show that besides the infrared cutoff at the horizon scale, the associated features of the primordial power spectrum around the horizon have a significant effect on improving the likelihood. The strong features are localized at the horizon scale.« less

Big-bang nucleosynthesis revisited

NASA Technical Reports Server (NTRS)

Olive, Keith A.; Schramm, David N.; Steigman, Gary; Walker, Terry P.

1989-01-01

The homogeneous big-bang nucleosynthesis yields of D, He-3, He-4, and Li-7 are computed taking into account recent measurements of the neutron mean-life as well as updates of several nuclear reaction rates which primarily affect the production of Li-7. The extraction of primordial abundances from observation and the likelihood that the primordial mass fraction of He-4, Y(sub p) is less than or equal to 0.24 are discussed. Using the primordial abundances of D + He-3 and Li-7 we limit the baryon-to-photon ratio (eta in units of 10 exp -10) 2.6 less than or equal to eta(sub 10) less than or equal to 4.3; which we use to argue that baryons contribute between 0.02 and 0.11 to the critical energy density of the universe. An upper limit to Y(sub p) of 0.24 constrains the number of light neutrinos to N(sub nu) less than or equal to 3.4, in excellent agreement with the LEP and SLC collider results. We turn this argument around to show that the collider limit of 3 neutrino species can be used to bound the primordial abundance of He-4: 0.235 less than or equal to Y(sub p) less than or equal to 0.245.

Why Were Polysaccharides Necessary?

NASA Astrophysics Data System (ADS)

Tolstoguzov, Vladimir

2004-12-01

The main idea of this paper is that the primordial soup may be modelled by food systems whose structure-property relationship is based on non-specific interactions between denatured biopolymers. According to the proposed hypothesis, polysaccharides were the first biopolymers that decreased concentration of salts in the primordial soup, `compatibilised' and drove the joint evolution of proto-biopolymers. Synthesis of macromolecules within the polysaccharide-rich medium could have resulted in phase separation of the primordial soup and concentration of the polypeptides and nucleic acids in the dispersed phase particles. The concentration of proto-biopolymer mixtures favoured their cross-linking in hybrid supermacromolecules of conjugates. The cross-linking of proto-biopolymers could occur by hydrophobic, electrostatic interactions, H-bonds due to freezing aqueous mixed biopolymer dispersions and/or by covalent bonds due to the Maillard reaction. Cross-linking could have increased the local concentration of chemically different proto-biopolymers, fixed their relative positions and made their interactions reproducible. Attractive-repulsive interactions between cross-linked proto-biopolymer chains could develop pairing of the monomer units, improved chemical stability (against hydrolysis) and led to their mutual catalytic activity and coding. Conjugates could probably evolve to the first self-reproduced entities and then to specialized cellular organelles. Phase separation of the primordial soup with concentration of conjugates in the dispersed particles has probably resulted in proto-cells.

Sleep and pulmonary outcomes for clinical trials of airway plexiform neurofibromas in NF1.

PubMed

Plotkin, Scott R; Davis, Stephanie D; Robertson, Kent A; Akshintala, Srivandana; Allen, Julian; Fisher, Michael J; Blakeley, Jaishri O; Widemann, Brigitte C; Ferner, Rosalie E; Marcus, Carole L

2016-08-16

Plexiform neurofibromas (PNs) are complex, benign nerve sheath tumors that occur in approximately 25%-50% of individuals with neurofibromatosis type 1 (NF1). PNs that cause airway compromise or pulmonary dysfunction are uncommon but clinically important. Because improvement in sleep quality or airway function represents direct clinical benefit, measures of sleep and pulmonary function may be more meaningful than tumor size as endpoints in therapeutic clinical trials targeting airway PN. The Response Evaluation in Neurofibromatosis and Schwannomatosis functional outcomes group reviewed currently available endpoints for sleep and pulmonary outcomes and developed consensus recommendations for response evaluation in NF clinical trials. For patients with airway PNs, polysomnography, impulse oscillometry, and spirometry should be performed to identify abnormal function that will be targeted by the agent under clinical investigation. The functional group endorsed the use of the apnea hypopnea index (AHI) as the primary sleep endpoint, and pulmonary resistance at 10 Hz (R10) or forced expiratory volume in 1 or 0.75 seconds (FEV1 or FEV0.75) as primary pulmonary endpoints. The group defined minimum changes in AHI, R10, and FEV1 or FEV0.75 for response criteria. Secondary sleep outcomes include desaturation and hypercapnia during sleep and arousal index. Secondary pulmonary outcomes include pulmonary resistance and reactance measurements at 5, 10, and 20 Hz; forced vital capacity; peak expiratory flow; and forced expiratory flows. These recommended sleep and pulmonary evaluations are intended to provide researchers with a standardized set of clinically meaningful endpoints for response evaluation in trials of NF1-related airway PNs. © 2016 American Academy of Neurology.

Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension

PubMed Central

Edgar, Alasdair J; Chacón, Matilde R; Bishop, Anne E; Yacoub, Magdi H; Polak, Julia M

2006-01-01

Background To elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH) and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH). Methods Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test. Results We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P < 0.01) compared with the housekeeping gene glyceraldehydes-3-phosphate dehydrogenase. Conclusion Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively. PMID:16390543

Sirolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas: a neurofibromatosis Clinical Trials Consortium phase II study.

PubMed

Weiss, Brian; Widemann, Brigitte C; Wolters, Pamela; Dombi, Eva; Vinks, Alexander; Cantor, Alan; Perentesis, John; Schorry, Elizabeth; Ullrich, Nicole; Gutmann, David H; Tonsgard, James; Viskochil, David; Korf, Bruce; Packer, Roger J; Fisher, Michael J

2015-04-01

Plexiform neurofibromas (PNs) are benign peripheral nerve sheath tumors that arise in one-third of individuals with neurofibromatosis type 1 (NF1). They may cause significant disfigurement, compression of vital structures, neurologic dysfunction, and/or pain. Currently, the only effective management strategy is surgical resection. Converging evidence has demonstrated that the NF1 tumor suppressor protein, neurofibromin, negatively regulates activity in the mammalian Target of Rapamycin pathway. We employed a 2-strata clinical trial design. Stratum 1 included subjects with inoperable, NF1-associated progressive PN and sought to determine whether sirolimus safely and tolerably increases time to progression (TTP). Volumetric MRI analysis conducted at regular intervals was used to determine TTP relative to baseline imaging. The estimated median TTP of subjects receiving sirolimus was 15.4 months (95% CI: 14.3-23.7 mo), which was significantly longer than 11.9 months (P < .001), the median TTP of the placebo arm of a previous PN clinical trial with similar eligibility criteria. This study demonstrated that sirolimus prolongs TTP by almost 4 months in patients with NF1-associated progressive PN. Although the improvement in TTP is modest, given the lack of significant or frequent toxicity and the availability of few other treatment options, the use of sirolimus to slow the growth of progressive PN could be considered in select patients. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Status of the PAPPA experiment

NASA Technical Reports Server (NTRS)

Kogut, Alan

2006-01-01

The Primordial Anisotropy Polarization Pathfinder Array (PAPPA) is a balloonborne instrument to measure the polarization of the cosmic microwave background and search for the signature of primordial gravity waves. PAPPA uses a novel marriage of RF phase modulation and millimeter-wave bolometric detectors to produce a "polarimeter-on-a-chip" capable of simultaneously measuring the Stokes I, Q, and U parameters on the sky. I will discuss the current status and future plans for PAPPA.

Is High Primordial Deuterium Consistent with Galactic Evolution?

NASA Astrophysics Data System (ADS)

Tosi, Monica; Steigman, Gary; Matteucci, Francesca; Chiappini, Cristina

1998-05-01

Galactic destruction of primordial deuterium is inevitably linked through star formation to the chemical evolution of the Galaxy. The relatively high present gas content and low metallicity suggest only modest D destruction. In concert with deuterium abundances derived from solar system and/or interstellar observations, this suggests a primordial deuterium abundance in possible conflict with data from some high-redshift, low-metallicity QSO absorbers. We have explored a variety of chemical evolution models including infall of processed material and early, supernovae-driven winds with the aim of identifying models with large D destruction that are consistent with the observations of stellar-produced heavy elements. When such models are confronted with data, we reconfirm that only modest destruction of deuterium (less than a factor of 3) is permitted. When combined with solar system and interstellar data, these results favor the low deuterium abundances derived for the QSO absorbers by Tytler et al.

Nebula-based Primordial Atmospheres of Planets Around Solar-Like Stars Revised

NASA Astrophysics Data System (ADS)

Scherf, Manuel; Lammer, H.; Leitzinger, M.; Odert, P.; Güdel, M.; Hanslmeier, A.

2012-05-01

At the beginning of a planetary system, in the stage of the stellar nebula and the growing-phase of the planets, planetesimals and Earth-like proto-planets accumulate a remarkable amount of gas, mainly consisting of hydrogen and helium. The mass of such a primordial atmosphere was first estimated for the proto-Earth by Hayashi et al. (1979), with up to 1026 g accumulated within 106 years. Furthermore it is commonly expected that these primordial atmospheres will be completely dissipated due to irradiation of the stellar EUV-flux during the first 108 years. Recent observations of young solar-like stars indicate that the efficiency and effect of the EUV-flux after the nebula disappeared, was highly overestimated by previous studies. We show that parts of these dense hydrogen/helium-gas envelopes may sustain this early active stage of a young star. Implications on the habitability are also discussed.

Testing the Standard Model with the Primordial Inflation Explorer

NASA Technical Reports Server (NTRS)

Kogut, Alan J.

2011-01-01

The Primordial Inflation Explorer is an Explorer-class mission to measure the gravity-wave signature of primordial inflation through its distinctive imprint on the linear polarization of the cosmic microwave background. PIXIE uses an innovative optical design to achieve background-limited sensitivity in 400 spectral channels spanning 2.5 decades in frequency from 30 GHz to 6 THz (1 cm to 50 micron wavelength). The principal science goal is the detection and characterization of linear polarization from an inflationary epoch in the early universe, with tensor-to-scalar ratio r < 10A{-3) at 5 standard deviations. The rich PIXIE data set will also constrain physical processes ranging from Big Bang cosmology to the nature of the first stars to physical conditions within the interstellar medium of the Galaxy. I describe the PIXIE instrument and mission architecture needed to detect the inflationary signature using only 4 semiconductor bolometers.

Inflation, Reionization, and All That: The Primordial Inflation Explorer

NASA Technical Reports Server (NTRS)

Kogut, Alan J.

2011-01-01

The Primordial Inflation Explorer is an Explorer-class mission to measure the gravity-wave signature of primordial inflation through its distinctive imprint on the linear polarization of the cosmic microwave background. PIXIE uses an innovative optical design to achieve background-limited sensitivity in 400 spectral channels spanning 2.5 decades in frequency from 30 GHz to 6 THz (1 cm to 50 micron wavelength). The principal science goal is the detection and characterization of linear polarization from an inflationary epoch in the early universe, with tensor-to-scalar ratio r less than l0^{-3) at 5 standard deviations. The rich PIXIE data set will also constrain physical processes ranging from Big Bang cosmology to the nature of the first stars to physical conditions within the interstellar medium of the Galaxy. I describe the PIXIE instrument and mission architecture needed to detect the inflationary signature using only 4 semiconductor bolometers.

The Primordial Inflation Explorer

NASA Technical Reports Server (NTRS)

Kogut, Alan J.

2012-01-01

The Primordial Inflation Explorer is an Explorer-class mission to measure the gravity-wave signature of primordial inflation through its distinctive imprint on the linear polarization of the cosmic microwave background. PIXIE uses an innovative optical design to achieve background-limited sensitivity in 400 spectral channels spanning 2.5 decades in frequency from 30 GHz to 6 THz (1 cm to 50 micron wavelength). The principal science goal is the detection and characterization of linear polarization from an inflationary epoch in the early universe, with tensor-to-scalar ratio r < 10(exp -3) at 5 standard deviations. The rich PIXIE data set will also constrain physical processes ranging from Big Bang cosmology to the nature of the first stars to physical conditions within the interstellar medium of the Galaxy. I describe the PIXIE instrument and mission architecture needed to detect the inflationary signature using only 4 semiconductor bolometers.

Inflation, Reionization, and All That: The Primordial Inflation Explorer

NASA Technical Reports Server (NTRS)

Kogut, Alan J.

2012-01-01

The Primordial Inflation Explorer is an Explorer-class mission to measure the gravity-wave signature of primordial inflation through its distinctive imprint on the linear polarization of the cosmic microwave background. PIXIE uses an innovative optical design to achieve background-limited sensitivity in 400 spectral channels spanning 2.5 decades in frequency from 30 GHz to 6 THz (1 cm to 50 micron wavelength). The principal science goal is the detection and characterization of linear polarization from an inflationary epoch in the early universe, with tensor-to-scalar ratio r < 10(exp -3) at 5 standard deviations. The rich PIXIE data set will also constrain physical processes ranging from Big Bang cosmology to the nature of the first stars to physical conditions within the interstellar medium of the Galaxy. I describe the PIXIE instrument and mission architecture needed to detect the inflationary signature using only 4 semiconductor bolometers.

Generically large nongaussianity in small multifield inflation

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

Bramante, Joseph

If forthcoming measurements of cosmic photon polarization restrict the primordial tensor-to-scalar ratio to r<0.01, small field inflation will be a principal candidate for the origin of the universe. Here we show that small multifield inflation, without the hybrid mechanism, typically results in large squeezed nongaussianity. Small multifield potentials contain multiple flat field directions, often identified with the gauge invariant field directions in supersymmetric potentials. We find that unless these field directions have equal slopes, large nongaussianity arises. After identifying relevant differences between large and small two-field potentials, we demonstrate that the latter naturally fulfill the Byrnes-Choi-Hall large nongaussianity conditions. Computationsmore » of the primordial power spectrum, spectral index, and squeezed bispectrum, reveal that small two-field models which otherwise match observed primordial perturbations, produce excludably large nongaussianity if the inflatons’ field directions have unequal slopes.« less

Generically large nongaussianity in small multifield inflation

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

Bramante, Joseph, E-mail: josephbramante@gmail.com

If forthcoming measurements of cosmic photon polarization restrict the primordial tensor-to-scalar ratio to r < 0.01, small field inflation will be a principal candidate for the origin of the universe. Here we show that small multifield inflation, without the hybrid mechanism, typically results in large squeezed nongaussianity. Small multifield potentials contain multiple flat field directions, often identified with the gauge invariant field directions in supersymmetric potentials. We find that unless these field directions have equal slopes, large nongaussianity arises. After identifying relevant differences between large and small two-field potentials, we demonstrate that the latter naturally fulfill the Byrnes-Choi-Hall large nongaussianity conditions. Computationsmore » of the primordial power spectrum, spectral index, and squeezed bispectrum, reveal that small two-field models which otherwise match observed primordial perturbations, produce excludably large nongaussianity if the inflatons' field directions have unequal slopes.« less

The possible influence of L-histidine on the origin of the first peptides on the primordial Earth.

PubMed

Reiner, Hannes; Plankensteiner, Kristof; Fitz, Daniel; Rode, Bernd Michael

2006-06-01

One of the most unsettled problems of prebiotic evolution and the origin of life is the explanation why one enantiomeric form of biomolecules prevailed. In the experiments presented in this paper, the influence of L-histidine on the peptide formation in the Salt-Induced Peptide Formation (SIPF) reaction of the enantiomeric forms of valine, proline, serine, lysine, and tryptophan, and the catalytic effects in this first step toward the first building blocks of proteins on the primordial earth were investigated. In the majority of the produced dipeptides, a remarkable increase of yields was shown, and the preference of the L-amino acids in the peptide formation in most cases cannot be denied. In summary, our data provide further experimental evidence for the plausibility of the SIPF reaction and point at a possible important role of L-histidine in the chemical evolution on the primordial Earth.

Shapes and features of the primordial bispectrum

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

Gong, Jinn-Ouk; Palma, Gonzalo A.; Sypsas, Spyros, E-mail: jinn-ouk.gong@apctp.org, E-mail: gpalmaquilod@ing.uchile.cl, E-mail: s.sypsas@gmail.com

If time-dependent disruptions from slow-roll occur during inflation, the correlation functions of the primordial curvature perturbation should have scale-dependent features, a case which is marginally supported from the cosmic microwave background (CMB) data. We offer a new approach to analyze the appearance of such features in the primordial bispectrum that yields new consistency relations and justifies the search of oscillating patterns modulated by orthogonal and local templates. Under the assumption of sharp features, we find that the cubic couplings of the curvature perturbation can be expressed in terms of the bispectrum in two specific momentum configurations, for example local andmore » equilateral. This allows us to derive consistency relations among different bispectrum shapes, which in principle could be tested in future CMB surveys. Furthermore, based on the form of the consistency relations, we construct new two-parameter templates for features that include all the known shapes.« less

Primordial germ cell biology at the beginning of the XXI century.

PubMed

De Felici, Massimo

2009-01-01

At the XIV Workshop on the Development and Function of the Reproductive Organs held at the Congress Centre of the University of Rome Tor Vergata, Monteporzio Catone, Rome, Italy, the introduction to the first session entitled Mammalian primordial germ cells dedicated to the memory of Anne McLaren, was the occasion for a concise review of the state of art of research on the biology of primordial germ cells (PGCs). This great, unforgettable scientist, who died in a car accident in July 2007, dedicated most of her studies to this field over the last 25 years. Topics briefly reviewed in this Meeting Report are: 1) how the germ line is determined; 2) what are the mechanisms underlying PGC migration; 3) to what extent PGC survival, proliferation and differentiation are cell autonomous or environmentally controlled processes and 4) how the potential for totipotency is retained in PGCs.

Introduction to big bang nucleosynthesis and modern cosmology

NASA Astrophysics Data System (ADS)

Mathews, Grant J.; Kusakabe, Motohiko; Kajino, Toshitaka

Primordial nucleosynthesis remains as one of the pillars of modern cosmology. It is the testing ground upon which many cosmological models must ultimately rest. It is our only probe of the universe during the important radiation-dominated epoch in the first few minutes of cosmic expansion. This paper reviews the basic equations of space-time, cosmology, and big bang nucleosynthesis. We also summarize the current state of observational constraints on primordial abundances along with the key nuclear reactions and their uncertainties. We summarize which nuclear measurements are most crucial during the big bang. We also review various cosmological models and their constraints. In particular, we analyze the constraints that big bang nucleosynthesis places upon the possible time variation of fundamental constants, along with constraints on the nature and origin of dark matter and dark energy, long-lived supersymmetric particles, gravity waves, and the primordial magnetic field.

Neglecting primordial non-Gaussianity threatens future cosmological experiment accuracy

NASA Astrophysics Data System (ADS)

Camera, Stefano; Carbone, Carmelita; Fedeli, Cosimo; Moscardini, Lauro

2015-02-01

Future galaxy redshift surveys aim at probing the clustering of the cosmic large-scale structure with unprecedented accuracy, thus complementing cosmic microwave background experiments in the quest to deliver the most precise and accurate picture ever of our Universe. Analyses of such measurements are usually performed within the context of the so-called vanilla Λ CDM model—the six-parameter phenomenological model which, for instance, emerges from best fits against the recent data obtained by the Planck satellite. Here, we show that such an approach is prone to subtle systematics when the Gaussianity of primordial fluctuations is concerned. In particular, we demonstrate that, if we neglect even a tiny amount of primordial non-Gaussianity—fully consistent with current limits—we shall introduce spurious biases in the reconstruction of cosmological parameters. This is a serious issue that must be properly accounted for in view of accurate (as well as precise) cosmology.

Primordial helium abundance determination using sulphur as metallicity tracer

NASA Astrophysics Data System (ADS)

Fernández, Vital; Terlevich, Elena; Díaz, Angeles I.; Terlevich, Roberto; Rosales-Ortega, F. F.

2018-05-01

The primordial helium abundance YP is calculated using sulphur as metallicity tracer in the classical methodology (with YP as an extrapolation of Y to zero metals). The calculated value, YP, S = 0.244 ± 0.006, is in good agreement with the estimate from the Planck experiment, as well as, determinations in the literature using oxygen as the metallicity tracer. The chemical analysis includes the sustraction of the nebular continuum and of the stellar continuum computed from simple stellar population synthesis grids. The S+2 content is measured from the near infrared [SIII]λλ9069Å, 9532Å lines, while an ICF(S3 +) is proposed based on the Ar3 +/Ar2 + fraction. Finally, we apply a multivariable linear regression using simultaneously oxygen, nitrogen and sulphur abundances for the same sample to determine the primordial helium abundance resulting in YP - O, N, S = 0.245 ± 0.007.