Deferoxamine retinopathy: spectral domain-optical coherence tomography findings

BACKGROUND: To describe the spectral domain optical coherence tomography (SD-OCT) findings of a patient who developed pigmentary retinopathy following high-dose deferoxamine administration. CASE PRESENTATION: A 34-year-old man with thalassemia major complained of nyctalopia and decreased vision following high-dose intravenous deferoxamine to treat systemic iron overload. Fundus examination revealed multiple discrete hypo-pigmented lesions at the posterior pole and mid-peripheral retina. Recovery was partial following cessation of desferrioxamine six weeks later. A follow-up SD-OCT showed multiple accumulated hyper-reflective deposits primarily in the choroid, retina pigment epithelium (RPE), and inner segment and outer segment (IS/OS) junction. CONCLUSION: Deferoxamine retinopathy primarily targets the RPE–Bruch membrane–photoreceptor complex, extending from the peri-fovea to the peripheral retina with foveola sparing. An SD-OCT examination can serve as a simple, noninvasive tool for early detection and long-term follow-up

Deferoxamine retinopathy: spectral domain-optical coherence tomography findings

Al-Djamiʿ li Ibn al-BaïtharNumérisation effectuée à partir d'un document de substitution

VIRAL RNA ELEMENTS AND HOST GENES AFFECTING RNA RECOMBINATION IN TOMBUSVIRUSES

RNA recombination is a major factor driving viral evolution and contributing to new disease outbreaks. Therefore, understanding the mechanism of RNA recombination can help scientists to develop longer lasting antiviral strategies. Tombusviruses are one of the best model RNA viruses to study RNA virus recombination. My goals were to dissect the mechanism of tombusviral RNA recombination. To do so, in my thesis, I describe my results on the roles of (i) the viral replicase and the viral RNA templates; and (ii) the effect of host factors on tombusvirus recombination events. To study the mechanism of RNA recombination without the influence of selection pressure on the emerging recombinants, we developed an in vitro RNA recombination assay based on viral RNA templates and purified viral replicase preparations. Using this in vitro assay, we demonstrated that replicase driven template switching is the mechanism of recombination, whereas RNA ligation seems less likely to be a major mechanism. In addition, we also studied the role of RNA substrates, in more detail. Our results showed that viral replicase preferred to use functional RNA domains in the acceptor RNAs over random switching events. Host factors may also play important roles in RNA recombination. Using yeast as a model system for studying replication and recombination of a tombusvirus replicon, we identified 9 host genes affecting tombusvirus RNA recombination. Separate deletion of five of these genes enhanced generation of novel viral RNA recombinants. Further studies on one of these genes, XRN1, a 5-3 exoribonuclease, indicated that it might be involved in degradation of tombusvirus RNAs. Lack of Xrn1p resulted in accumulation of truncated (partially degraded) replicon RNAs, which became good templates for RNA recombination. To further study Xrn1p, we overexpressed Xrn4p of Arabidopsis thaliana, a functional analogue of the yeast Xrn1p, in Nicotiana benthamiana plants. After superinfecting the Xrn4p-overexpressing N. benthamiana with tombusvirus, truncated tombusvirus genomic and subgenomic RNA1 were observed. Some of the identified tombusvirus variants were infectious in protoplasts and could systemically infected N. benthamiana plants. Overall, this is the first report that a single host gene can affect rapid viral evolution and RNA recombination

The Nuclear Chaperone Nucleophosmin Escorts an Epstein-Barr Virus Nuclear Antigen to Establish Transcriptional Cascades for Latent Infection in Human B Cells

Epstein-Barr Virus (EBV) is an oncogenic γ-herpesvirus that capably establishes both latent and lytic modes of infection in host cells and causes malignant diseases in humans. Nuclear antigen 2 (EBNA2)-mediated transcription of both cellular and viral genes is essential for the establishment and maintenance of the EBV latency program in B lymphocytes. Here, we employed a protein affinity pull-down and LC-MS/MS analysis to identify nucleophosmin (NPM1) as one of the cellular proteins bound to EBNA2. Additionally, the specific domains that are responsible for protein-protein interactions were characterized as EBNA2 residues 300 to 360 and the oligomerization domain (OD) of NPM1. As in c-MYC, dramatic NPM1 expression was induced in EBV positively infected B cells after three days of viral infection, and both EBNA2 and EBNALP were implicated in the transactivation of the NPM1 promoter. Depletion of NPM1 with the lentivirus-expressed short-hairpin RNAs (shRNAs) effectively abrogated EBNA2-dependent transcription and transformation outgrowth of lymphoblastoid cells. Notably, the ATP-bound state of NPM1 was required to induce assembly of a protein complex containing EBNA2, RBP-Jκ, and NPM1 by stabilizing the interaction of EBNA2 with RBP-Jκ. In a NPM1-knockdown cell line, we demonstrated that an EBNA2-mediated transcription defect was fully restored by the ectopic expression of NPM1. Our findings highlight the essential role of NPM1 in chaperoning EBNA2 onto the latency-associated membrane protein 1 (LMP1) promoters, which is coordinated with the subsequent activation of transcriptional cascades through RBP-Jκ during EBV infection. These data advance our understanding of EBV pathology and further imply that NPM1 can be exploited as a therapeutic target for EBV-associated diseases

Assessing the quality of steady-state visual-evoked potentials for moving humans using a mobile electroencephalogram headset.

Recent advances in mobile electroencephalogram (EEG) systems, featuring non-prep dry electrodes and wireless telemetry, have enabled and promoted the applications of mobile brain-computer interfaces (BCIs) in our daily life. Since the brain may behave differently while people are actively situated in ecologically-valid environments versus highly-controlled laboratory environments, it remains unclear how well the current laboratory-oriented BCI demonstrations can be translated into operational BCIs for users with naturalistic movements. Understanding inherent links between natural human behaviors and brain activities is the key to ensuring the applicability and stability of mobile BCIs. This study aims to assess the quality of steady-state visual-evoked potentials (SSVEPs), which is one of promising channels for functioning BCI systems, recorded using a mobile EEG system under challenging recording conditions, e.g., walking. To systematically explore the effects of walking locomotion on the SSVEPs, this study instructed subjects to stand or walk on a treadmill running at speeds of 1, 2, and 3 mile (s) per hour (MPH) while concurrently perceiving visual flickers (11 and 12 Hz). Empirical results of this study showed that the SSVEP amplitude tended to deteriorate when subjects switched from standing to walking. Such SSVEP suppression could be attributed to the walking locomotion, leading to distinctly deteriorated SSVEP detectability from standing (84.87 ± 13.55%) to walking (1 MPH: 83.03 ± 13.24%, 2 MPH: 79.47 ± 13.53%, and 3 MPH: 75.26 ± 17.89%). These findings not only demonstrated the applicability and limitations of SSVEPs recorded from freely behaving humans in realistic environments, but also provide useful methods and techniques for boosting the translation of the BCI technology from laboratory demonstrations to practical applications

Be Stars in the Open Cluster NGC 6830

We report the discovery of 2 new Be stars, and re-identify one known Be star in the open cluster NGC 6830. Eleven H-alpha emitters were discovered using the H-alpha imaging photometry of the Palomar Transient Factory Survey. Stellar membership of the candidates was verified with photometric and kinematic information using 2MASS data and proper motions. The spectroscopic confirmation was carried out by using the Shane 3-m telescope at Lick observatory. Based on their spectral types, three H-alpha emitters were confirmed as Be stars with H-alpha equivalent widths > -10 Angstrom. Two objects were also observed by the new spectrograph SED-Machine on the Palomar 60 inch Telescope. The SED-Machine results show strong H-alpha emission lines, which are consistent with the results of the Lick observations. The high efficiency of the SED-Machine can provide rapid observations for Be stars in a comprehensive survey in the future.Comment: 11 pages, 8 figures, AJ in pres

The Enhanced metastatic potential of hepatocellular carcinoma (HCC) cells with sorafenib resistance

Acquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR) cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3) were first performed to confirm the resistance of cells. Migration and invasion assays, and immunoblotting analysis on the expression of epithelial to mesenchymal transition (EMT) regulatory proteins were performed to study the metastatic potential of SorR cells. The expression of CD44 and CD133 were studied by flow cytometry and the gene expressions of pluripotency factors were studied by qPCR to demonstrate the enrichment of cancer stem cells (CSCs) in SorR cells. Control (CTL) and SorR cells were also injected orthotopically to the livers of NOD-SCID mice to investigate the development of lung metastasis. Increased expressions of ABCC1-3 were found in SorR cells. Enhanced migratory and invasive abilities of SorR cells were observed. The changes in expression of EMT regulatory proteins demonstrated an activation of the EMT process in SorR cells. Enriched proportion of CD44+ and CD44+CD133 + cells were also observed in SorR cells. All (8/8) mice injected with SorR cells demonstrated lung metastasis whereas only 1/8 mouse injected with CTL cells showed lung metastasis. HCC cells with sorafenib resistance demonstrated a higher metastatic potential, which may be due to the activated EMT process. Enriched CSCs were also demonstrated in the sorafenib resistant cells. This study suggests that advanced HCC patients with acquired sorafenib resistance may have enhanced tumor growth or distant metastasis, which raises the concern of long-term sorafenib treatment in advanced HCC patients who have developed resistance of sorafenib. © 2013 Chow et al.published_or_final_versio