The spectrum of eye disease in hospitalized adults living with HIV, 1995-2010.

Eye disease is a well-documented complication of HIV infection. Opportunistic infections generally comprised the majority of pre-antiretroviral therapy (ART) eye complications. With the introduction of ART, opportunistic infections diminished. However, early ART regimens were cumbersome regarding side effects and pill burden, making patient compliance difficult. Newer ART regimens are better tolerated and consist of fewer pills, theoretically making compliance easier and therapy more effective. The aim of this chart review study is to examine eye disease epidemiology in HIV patients as ART has evolved. We reviewed 222 admissions at Thomas Jefferson University Hospitals for 188 patients. These cases were divided into two groups. The first group was comprised of patients admitted from 1995 through 2003, while the second group consisted of patients admitted from 2003 to 2010. Eye disease epidemiology was compared between the two groups. Our study did note a significant decrease in eye diseases caused by opportunistic infections in the 2003-2010 patient group. Noninfectious eye disease is a significant complication in this group

Type I feline coronavirus spike glycoprotein fails to recognize aminopeptidase N as a functional receptor on feline cell lines

There are two types of feline coronaviruses that can be distinguished by serology and sequence analysis. Type I viruses, which are prevalent in the field but are difficult to isolate and propagate in cell culture, and type II viruses, which are less prevalent but replicate well in cell culture. An important determinant of coronavirus infection, in vivo and in cell culture, is the interaction of the virus surface glycoprotein with a cellular receptor. It is generally accepted that feline aminopeptidase N can act as a receptor for the attachment and entry of type II strains, and it has been proposed that the same molecule acts as a receptor for type I viruses. However, the experimental data are inconclusive. The aim of the studies reported here was to provide evidence for or against the involvement of feline aminopeptidase N as a receptor for type I feline coronaviruses. Our approach was to produce retroviral pseudotypes that bear the type I or type II feline coronavirus surface glycoprotein and to screen a range of feline cell lines for the expression of a functional receptor for attachment and entry. Our results show that type I feline coronavirus surface glycoprotein fails to recognize feline aminopeptidase N as a functional receptor on three continuous feline cell lines. This suggests that feline aminopeptidase N is not a receptor for type I feline coronaviruses. Our results also indicate that it should be possible to use retroviral pseudotypes to identify and characterize the cellular receptor for type I feline coronaviruses

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

An analysis on the variability of the tilapia lake virus (TiLV) whole genome to aid in detection and treatment target

Tilapia is one of the most important farmed fish worldwide for its affordability, marketability, adaptability, and hardiness in resisting disease. However, huge losses of cultured tilapia in an Israeli tilapia farm led to the discovery of the tilapia lake virus (TiLV) in 2014. It has since spread to four (4) continents and sixteen (16) countries, causing a huge threat to the global tilapia aquaculture industry for its high mortality rates reaching up to 90%. As a novel virus, much of its basic foundation is still unknown, including its genetic information and variability that has led to its rapid spread. Thus, the study aims to learn about the genetic variability of the TiLV genome to aid in detection and treatment target. An evaluation on the genomic variability was conducted through MEGA11 on twenty-two (22) TiLV genomes collected from eight (8) countries over a decade. It was found through pairwise distance estimation that segments 9 and 10 of the TiLV genome have remained largely conserved, making it a good target for virus detection. Four (4) primers each for both segments were chosen out of seventy-one (71) designed primers through NCBI Primer-BLAST with a GC% content between 50-60 and specificity for selected strains of well-supported nodes in the segments’ phylogenetic tree (lnL = -1116.19 and -1162.96, bootstrap valuesremoved). For the treatment target, the most conserved regions could not be fully evaluated due to the unknown properties of the hypothetical proteins, so the relatively conserved segment 1 coding for the putative PB1 gene was determined as the best treatment target. It was also found that the nucleotide frequency of a strain from Israel collected in 2011 (Til-4-2011) displayed a vastly different pattern compared to the rest of the sequences. The findings of this study are significant as it was able to establish certain genetic information that was previously lacking, including the genetic variation between the segments to determine the most conserved and varied regions, as well as the nucleotide compositions between the different strains. Geographical origin was also found to play a role in the reassortment of the virus as well-supported clades tended to come from the same region

In Vitro Studies of Steriodogenic Factor-1 Sumoylation, a Post-translational Modification Critical for Adrenal and Gonadal Development

Steroidogenic Factor-1 (SF-1) is a constitutively active nuclear hormone receptor, thus its post-translational modifications play an even more important role in its regulation. SF-1 is sumoylated at two sites, K119 and K194 of which the former has been shown to determine SF-1 binding specificity to sumo-sensitive response elements. The basic enzymology behind sumoylation of SF-1 K119 sumoylation is not fully understood nor optimized with the reaction taking well over 8 hours while still not reaching completion. Similarly, sensitive visualization assays are not currently available in order to facilitate kinetic studies of this in vitro reaction. This graduate work focuses on sumoylation of the SF-1 DBD with the goal of developing a more robust and sensitive in vitro system in order to assay new potential SF-1 binding sequences and apply the revamped protocol to other sumoylation substrates. Our work demonstrates that the rate-limiting step of the enzymatic reaction is the loading of the E2 enzyme, Ubc9, and pre-loading this enzyme prior to incubation with substrate dramatically enhances the rate of sumoylation. Finally, we attempt to determine how the putative E3 ligase, PIASγ, functions to enhance SF-1 sumoylation in vitro

An automated client tracking and file management system for National Telecommunications Commission Regional Office Number 4

An automated customized application for the Licensing Section of the National Telecommunications Commission (NTC) of Region IV is presented and developed using the Foxpro programming tool. The analysis and detailed description of the system, as well as the complete code listings are presented in the study. The system aims to minimize the errors that are encountered in NTC Region IV by personnel with regards to data integrity, data corruption, data loss, and generation of reports