Role of a 19S Proteasome Subunit- PSMD10(Gankyrin) in Neurogenesis of Human Neuronal Progenitor Cells

PSMD10(Gankyrin), a proteasome assembly chaperone, is a widely known oncoprotein which aspects many hall mark properties of cancer. However, except proteasome assembly chaperon function its role in normal cell function remains unknown. To address this issue, we induced PSMD10(Gankyrin) overexpression in HEK293 cells and the resultant large-scale changes in gene expression profile were analyzed. We constituted networks from microarray data of these differentially expressed genes and carried out extensive topological analyses. The overrecurring yet consistent theme that appeared throughout analysis using varied network metrics is that all genes and interactions identified as important would be involved in neurogenesis and neuronal development. Intrigued we tested the possibility that PSMD10(Gankyrin) may be strongly associated with cell fate decisions that commit neural stem cells to differentiate into neurons. Overexpression of PSMD10(Gankyrin) in human neuronal progenitor cells facilitated neuronal differentiation via beta-catenin Ngn1 pathway. Here for the first time we provide preliminary and yet compelling experimental evidence for the involvement of a potential oncoprotein - PSMD10(Gankyrin), in neuronal differentiation

Corrigendum to “Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules” [FEBS Open Bio 4 (2014) 571–583]

10.1016/j.fob.2015.06.010FEBS Open Bio5731-73

In-orbit Performance of UVIT on ASTROSAT

We present the in-orbit performance and the first results from the ultra-violet Imaging telescope (UVIT) on ASTROSAT. UVIT consists of two identical 38cm coaligned telescopes, one for the FUV channel (130-180nm) and the other for the NUV (200-300nm) and VIS (320-550nm) channels, with a field of view of 28 $arcmin$. The FUV and the NUV detectors are operated in the high gain photon counting mode whereas the VIS detector is operated in the low gain integration mode. The FUV and NUV channels have filters and gratings, whereas the VIS channel has filters. The ASTROSAT was launched on 28th September 2015. The performance verification of UVIT was carried out after the opening of the UVIT doors on 30th November 2015, till the end of March 2016 within the allotted time of 50 days for calibration. All the on-board systems were found to be working satisfactorily. During the PV phase, the UVIT observed several calibration sources to characterise the instrument and a few objects to demonstrate the capability of the UVIT. The resolution of the UVIT was found to be about 1.4 - 1.7 $arcsec$ in the FUV and NUV. The sensitivity in various filters were calibrated using standard stars (white dwarfs), to estimate the zero-point magnitudes as well as the flux conversion factor. The gratings were also calibrated to estimate their resolution as well as effective area. The sensitivity of the filters were found to be reduced up to 15\% with respect to the ground calibrations. The sensitivity variation is monitored on a monthly basis. UVIT is all set to roll out science results with its imaging capability with good resolution and large field of view, capability to sample the UV spectral region using different filters and capability to perform variability studies in the UV.Comment: 10 pages, To appear in SPIE conference proceedings, SPIE conference paper, 201

UBQLN2 mediates autophagy-independent protein aggregate clearance by the proteasome

Clearance of misfolded and aggregated proteins is central to cell survival. Here, we describe a new pathway for maintaining protein homeostasis mediated by the proteasome shuttle factor UBQLN2. The 26S proteasome degrades polyubiquitylated substrates by recognizing them through stoichiometrically bound ubiquitin receptors, but substrates are also delivered by reversibly bound shuttles. We aimed to determine why these parallel delivery mechanisms exist and found that UBQLN2 acts with the HSP70-HSP110 disaggregase machinery to clear protein aggregates via the 26S proteasome. UBQLN2 recognizes client-bound HSP70 and links it to the proteasome to allow for the degradation of aggregated and misfolded proteins. We further show that this process is active in the cell nucleus, where another system for aggregate clearance, autophagy, does not act. Finally, we found that mutations in UBQLN2, which lead to neurodegeneration in humans, are defective in chaperone binding, impair aggregate clearance, and cause cognitive deficits in mice

Pressure injectors for radiologists: A review and what is new

Pressure Injectors are used routinely in diagnostic and interventional radiology. Advances in medical science and technology have made it is imperative for both diagnostic as well as interventional radiologists to have a thorough understanding of the various aspects of pressure injectors. Further, as many radiologists may not be fully conversant with injections into ports, central lines and PICCs, it is important to familiarize oneself with the same. It is also important to follow stringent operating protocols during the use of pressure injectors to prevent complications such as contrast extravastion, sepsis and air embolism. This article aims to update existing knowledge base in this respect

Imaging and interventions in idiopathic intracranial hypertension: A pictorial essay

Intracranial hypertension is a syndrome of elevated intracranial pressure that can be primary or secondary. The primary form, now termed idiopathic intracranial hypertension (IIH), was in the past a disease of exclusion and imaging played a limited role of excluding organic causes of raised intracranial pressure. However imaging markers have been described with patients with IIH at the orbit, sella and cerebral venous system. We wish to reiterate the characteristic imaging features of this poorly understood disease and also emphasise that stenting of the transverse sinus in select cases of IIH is an efficacious option

Dry imaging cameras

Dry imaging cameras are important hard copy devices in radiology. Using dry imaging camera, multiformat images of digital modalities in radiology are created from a sealed unit of unexposed films. The functioning of a modern dry camera, involves a blend of concurrent processes, in areas of diverse sciences like computers, mechanics, thermal, optics, electricity and radiography. Broadly, hard copy devices are classified as laser and non laser based technology. When compared with the working knowledge and technical awareness of different modalities in radiology, the understanding of a dry imaging camera is often superficial and neglected. To fill this void, this article outlines the key features of a modern dry camera and its important issues that impact radiology workflow

Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules

AbstractPSMD9 (Proteasome Macropain non-ATPase subunit 9), a proteasomal assembly chaperone, harbors an uncharacterized PDZ-like domain. Here we report the identification of five novel interacting partners of PSMD9 and provide the first glimpse at the structure of the PDZ-domain, including the molecular details of the interaction. We based our strategy on two propositions: (a) proteins with conserved C-termini may share common functions and (b) PDZ domains interact with C-terminal residues of proteins. Screening of C-terminal peptides followed by interactions using full-length recombinant proteins, we discovered hnRNPA1 (an RNA binding protein), S14 (a ribosomal protein), CSH1 (a growth hormone), E12 (a transcription factor) and IL6 receptor as novel PSMD9-interacting partners. Through multiple techniques and structural insights, we clearly demonstrate for the first time that human PDZ domain interacts with the predicted Short Linear Sequence Motif (SLIM) at the C-termini of the client proteins. These interactions are also recapitulated in mammalian cells. Together, these results are suggestive of the role of PSMD9 in transcriptional regulation, mRNA processing and editing, hormone and receptor activity and protein translation. Our proof-of-principle experiments endorse a novel and quick method for the identification of putative interacting partners of similar PDZ-domain proteins from the proteome and for discovering novel functions

Synthetic Uncleavable Ubiquitinated Proteins Dissect Proteasome Deubiquitination and Degradation, and Highlight Distinctive Fate of Tetraubiquitin

Various hypotheses have been proposed regarding how chain length, linkage type, position on substrate, and susceptibility to deubiquitinases (DUBs) affect processing of different substrates by proteasome. Here we report a new strategy for the chemical synthesis of ubiquitinated proteins to generate a set of well-defined conjugates bearing an oxime bond between the chain and the substrate. We confirmed that this isopeptide replacement is resistant to DUBs and to shaving by proteasome. Analyzing products generated by proteasomes ranked how chain length governed degradation outcome. Our results support that (1) the cleavage of the proximal isopeptide bond is not a prerequisite for proteasomal degradation, (2) by overcoming trimming at the proteasome, tetraUb is a fundamentally different signal than shorter chains, and (3) the tetra-ubiquitin chain can be degraded with the substrate. Together these results highlight the usefulness of chemistry to dissect the contribution of proteasome-associated DUBs and the complexity of the degradation process