Diabetic Retinopathy- Brief Overview

Diabetic retinopathy (DR) is a major complication of diabetes, which affects over 90 million people worldwide. Lifetime occurrence of DR is over 90% and 50-60% for Type I diabetes mellitus (T1DM) and T2DM, respectively. Such a high prevalence makes DR a leading cause of blindness in working aged people and a major public health issue in developed countries. In the inaugural issue, this editorial provides a brief overview of the salient features of DR, including risk factors, diagnosis, pathobiology, molecular and cellular mechanisms, and therapeutics. Aspects of DR that are critically important, but not commonly known, will also be discussed

7-Ketocholesterol Induces Autophagy in Vascular Smooth Muscle Cells through Nox4 and Atg4B

Oxidized lipoproteins stimulate autophagy in advanced atherosclerotic plaques. However, the mechanisms underlying autophagy induction and the role of autophagy in atherogenesis remain to be determined. This study was designed to investigate the mechanisms by which 7-ketocholesterol (7-KC), a major component of oxidized lipoproteins, induces autophagy. This study was also designed to determine the effect of autophagy induction on apoptosis, a central event in the development of atherosclerosis. Exposure of human aortic smooth muscle cells to 7-KC increased autophagic flux. Autophagy induction was suppressed by treating the cells with either a reactive oxygen species scavenger or an antioxidant. Administration of 7-KC concomitantly up-regulated Nox4 expression, increased intracellular hydrogen peroxide levels, and inhibited autophagy-related gene 4B activity. Catalase overexpression to remove hydrogen peroxide or Nox4 knockdown with siRNA reduced intracellular hydrogen peroxide levels, restored autophagy-related gene 4B activity, and consequently attenuated 7-KC–induced autophagy. Moreover, inhibition of autophagy aggravated both endoplasmic reticulum (ER) stress and cell death in response to 7-KC. In contrast, up-regulation of autophagic activity by rapamycin had opposite effects. Finally, activation of autophagy by chronic rapamycin treatment attenuated ER stress, apoptosis, and atherosclerosis in apolipoprotein E knockout (ApoE−/−) mouse aortas. In conclusion, we demonstrate that up-regulation of autophagy is a cellular protective response that attenuates 7-KC–induced cell death in human aortic smooth muscle cells

Stability of a Long Noncoding Viral RNA Depends on a 9-nt Core Element at the RNA 5' End to Interact with Viral ORF57 and Cellular PABPC1

Kaposi sarcoma-associated herpesvirus (KSHV) ORF57, also known as Mta (mRNA transcript accumulation), enhances viral intron-less transcript accumulation and promotes splicing of intron-containing viral RNA transcripts. In this study, we identified KSHV PAN, a long non-coding polyadenylated nuclear RNA as a main target of ORF57 by a genome-wide CLIP (cross-linking and immunoprecipitation) approach. KSHV genome lacking ORF57 expresses only a minimal amount of PAN. In cotransfection experiments, ORF57 alone increased PAN expression by 20-30-fold when compared to vector control. This accumulation function of ORF57 was dependent on a structured RNA element in the 5' PAN, named MRE (Mta responsive element), but not much so on an ENE (expression and nuclear retention element) in the 3' PAN previously reported by other studies. We showed that the major function of the 5' PAN MRE is increasing the RNA half-life of PAN in the presence of ORF57. Further mutational analyses revealed a core motif consisting of 9 nucleotides in the MRE-II , which is responsible for ORF57 interaction and function. The 9-nt core in the MRE-II also binds cellular PABPC1, but not the E1B-AP5 which binds another region of the MRE-II. In addition, we found that PAN RNA is partially exportable in the presence of ORF57. Together, our data provide compelling evidence as to how ORF57 functions to accumulate a non-coding viral RNA in the course of virus lytic infection

Decomposing Star Formation and Active Galactic Nucleus with Spitzer Mid-Infrared Spectra: Luminosity Functions and Co-Evolution

We present Spitzer 7-38um spectra for a 24um flux limited sample of galaxies at z~0.7 in the COSMOS field. The detailed high-quality spectra allow us to cleanly separate star formation (SF) and active galactic nucleus (AGN) in individual galaxies. We first decompose mid-infrared Luminosity Functions (LFs). We find that the SF 8um and 15um LFs are well described by Schechter functions. AGNs dominate the space density at high luminosities, which leads to the shallow bright-end slope of the overall mid-infrared LFs. The total infrared (8-1000um) LF from 70um selected galaxies shows a shallower bright-end slope than the bolometrically corrected SF 15um LF, owing to the intrinsic dispersion in the mid-to-far-infrared spectral energy distributions. We then study the contemporary growth of galaxies and their supermassive black holes (BHs). Seven of the 31 Luminous Infrared Galaxies with Spitzer spectra host luminous AGNs, implying an AGN duty cycle of 23+/-9%. The time-averaged ratio of BH accretion rate and SF rate matches the local M_BH-M_bulge relation and the M_BH-M_host relation at z ~ 1. These results favor co-evolution scenarios in which BH growth and intense SF happen in the same event but the former spans a shorter lifetime than the latter. Finally, we compare our mid-infrared spectroscopic selection with other AGN identification methods and discuss candidate Compton-thick AGNs in the sample. While only half of the mid-infrared spectroscopically selected AGNs are detected in X-ray, ~90% of them can be identified with their near-infrared spectral indices.Comment: ApJ Accepted. emulateapj style. 16 pages, 9 figures, 4 table

Acceleration of on-axis and ring-shaped electron beams in wakefields driven by Laguerre-Gaussian pulses

The acceleration of electron beams with multiple transverse structures in wakefields driven by Laguerre-Gaussian pulses has been studied through three-dimensional (3D) particle-in-cell simulations. Under different laser-plasma conditions, the wakefield shows different transverse structures. In general cases, the wakefield shows a donut-like structure and it accelerates the ring-shaped hollow electron beam. When a lower plasma density or a smaller laser spot size is used, besides the donut-like wakefield, a central bell-like wakefield can also be excited. The wake sets in the center of the donut-like wake. In this case, both a central on-axis electron beam and a ring-shaped electron beam are simultaneously accelerated. Further, reducing the plasma density or laser spot size leads to an on-axis electron beam acceleration only. The research is beneficial for some potential applications requiring special pulse beam structures, such as positron acceleration and collimation

Acceleration and evolution of a hollow electron beam in wakefields driven by a Laguerre-Gaussian laser pulse

We show that a ring-shaped hollow electron beam can be injected and accelerated by using a Laguerre-Gaussian laser pulse and ionization-induced injection in a laser wakefield accelerator. The acceleration and evolution of such a hollow, relativistic electron beam are investigated through three-dimensional particle-in-cell simulations. We find that both the ring size and the beam thickness oscillate during the acceleration. The beam azimuthal shape is angularly dependent and evolves during the acceleration. The beam ellipticity changes resulting from the electron angular momenta obtained from the drive laser pulse and the focusing forces from the wakefield. The dependence of beam ring radius on the laser-plasma parameters (e.g., laser intensity, focal size, and plasma density) is studied. Such a hollow electron beam may have potential applications for accelerating and collimating positively charged particles

Study of a homogeneous QSO sample: relations between the QSO and its host galaxy

We analyse a sample of 69 QSOs which have been randomly selected in a complete sample of 104 QSOs (R<18, 0.142 < z < 0.198). 60 have been observed with the NTT/SUSI2 at La Silla, through two filters in the optical band (WB#655 and V#812), and the remaining 9 are taken from archive databases. The filter V#812 contains the redshifted Hbeta and forbidden [OIII] emission lines, while WB#655 covers a spectral region devoid of emission lines, thus measuring the QSO and stellar continua. The contributions of the QSO and the host are separated thanks to the MCS deconvolution algorithm, allowing a morphological classification of the host, and the computation of several parameters such as the host and nucleus absolute V-magnitude, distance between the luminosity center of the host and the QSO, and colour of the host and nucleus. We define a new asymmetry coefficient, independent of any galaxy models and well suited for QSO host studies. The main results from this study are: (i) 25% of the total number of QSO hosts are spirals, 51% are ellipticals and 60% show signs of interaction; (ii) Highly asymmetric systems tend to have a higher gas ionization level (iii) Elliptical hosts contain a substantial amount of ionized gas, and some show off-nuclear activity. These results agree with hierarchical models merger driven evolution.Comment: accepted for publication in MNRAS, 19 pages, 22 figures, 8 table