MCV Truncated Large T antigen interacts with BRD4 in tumors.

Among Polyomaviridae family of viruses, Merkel Cell Polyomavirus (MCV) is the only human polyomavirus with convincing data supporting its classification as a direct causative agent of a human skin malignancy, Merkel Cell Carcinoma. Oncogenic transformation by MCV requires the integration of the viral genome into the human genome, truncation of the large T antigen (LT) to render the viral genome replication deficient and expression of small T antigen oncoprotein. The chromatin binding protein BRD4, was recently shown to transcriptionally regulate the expression of virus oncoproteins, thereby enhancing the tumorigenesis of virus-associated cancers, such as HPV associated cervical cancer. Previous work by Wang et al. revealed that BRD4 interacts with MCV full length LT during viral replication. In this study, we demonstrated that MCV truncated tumor LT antigen also interacts with BRD4 protein. We showed that the MCV tumor LT antigen and BRD4 protein complex co-localizes within the nucleus. Furthermore, we tested whether BRD4 protein transcriptionally regulates MCV Non Coding Control Region (NCCR), where we found that though full length LT and sT together, along with the BRD4 protein showed enhanced transcriptional activity whereas tumor truncated LT did not. These findings on the interactions of the MCV tumor truncated LT antigen with the BRD4 protein add to existing knowledge about interactions with LT and its role in tumorigenesis, and assist in efforts to more precisely define new therapy targets for this disease

An acridine derivative, [4,5-bis{(N-carboxy methyl imidazolium)methyl}acridine] dibromide, shows anti-TDP-43 aggregation effect in ALS disease models

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with aggregation of TAR DNA-binding protein-43 (TDP-43) in neuronal cells and manifests as motor neuron dysfunction & muscle atrophy. The carboxyl-terminal prion-like domain of TDP-43 can aggregate in vitro into toxic β-sheet rich amyloid-like structures. So far, treatment options for ALS are very limited and Riluzole, which targets glutamate receptors, is the only but highly ineffective drug. Therefore, great interest exists in developing molecules for ALS treatment. Here, we have examined certain derivatives of acridine containing same side chains at position 4 & 5, for inhibitory potential against TDP-43 aggregation. Among several acridine derivatives examined, AIM4, which contains polar carboxyl groups in the side arms, significantly reduces TDP-43-YFP aggregation in the powerful yeast model cell and also abolishes in vitro amyloid-like aggregation of carboxyl terminal domain of TDP-43, as observed by AFM imaging. Thus, AIM4 can be a lead molecule potentiating further therapeutic research for ALS

Distinguishing Lightweight Block Ciphers in Encrypted Images

Modern day lightweight block ciphers provide powerful encryption methods for securing IoT communication data. Tiny digital devices exchange private data which the individual users might not be willing to get disclosed. On the other hand, the adversaries try their level best to capture this private data. The first step towards this is to identify the encryption scheme. This work is an effort to construct a distinguisher to identify the cipher used in encrypting the traffic data. We try to establish a deep learning based method to identify the encryption scheme used from a set of three lightweight block ciphers viz. LBlock, PRESENT and SPECK. We make use of images from MNIST and fashion MNIST data sets for establishing the cryptographic distinguisher. Our results show that the overall classification accuracy depends firstly on the type of key used in encryption and secondly on how frequently the pixel values change in original input image

Interplay of Structural, Optical and Magnetic properties in Gd doped CeO2

In this research wok systematic investigation on the synthesis, characterization, optical and magnetic properties of Ce1-xGdxO2 (where x=0.02, 0.04, 0.06, and 0.10) synthesized using the Solid-state method. Structural, Optical and Magnetic properties of the samples were investigated by X-ray diffraction (XRD), UV-VIS-NIR spectroscopy and VSM. Fluorite structure is confirmed from the XRD measurement on Gd doped CeO2 samples. Magnetic studies showed that the Gd doped polycrystalline samples display room temperature ferromagnetism and the ferromagnetic ordering strengthens with the Gd concentration

Non-Markovian Decay of a Three Level Cascade Atom in a Structured Reservoir

We present a formalism that enables the study of the non-Markovian dynamics of a three-level ladder system in a single structured reservoir. The three-level system is strongly coupled to a bath of reservoir modes and two quantum excitations of the reservoir are expected. We show that the dynamics only depends on reservoir structure functions, which are products of the mode density with the coupling constant squared. This result may enable pseudomode theory to treat multiple excitations of a structured reservoir. The treatment uses Laplace transforms and an elimination of variables to obtain a formal solution. This can be evaluated numerically (with the help of a numerical inverse Laplace transform) and an example is given. We also compare this result with the case where the two transitions are coupled to two separate structured reservoirs (where the example case is also analytically solvable)

Magnetocaloric effect and piezoresponse of engineered ferroelectric-ferromagnetic heterostructures

This study reports the magnetocaloric effect (MCE) and piezoresponse of integrated ferroelectric-ferromagnetic heterostructures of PbZr0.52Ti0.48O3 (PZT) (5 nm)/Bi-Sr-Ca-Cu-2-O-x (BSCCO) (5 nm)/La0.67Sr0.33MnO3 (LSMO) (40 nm)/MgO (0 01). Magnetic and pizoresponse behavior of the heterostructures are found to be governed by magneto-electric coupling and induced lattice strains. In addition, a maximum MCE is studied using Maxwell equations from both Field Cooled (FC) and Zero Field Cooled (ZFC) magnetization data. Maximum MCE entropy change (vertical bar Delta s vertical bar) of 42.6 mJkg(-1)K(-1) (at 258 K) and 41.7 mJkg(-1)K(-1) (at 269 K) are found corresponding to FC and ZFC data, respectively. The variation in maximum entropy change and corresponding temperatures for FC and ZFC data revealed that the application of a magnetic field can significantly contribute towards tuning of the MCE. Interestingly, these multilayered structures are found to sustain MCE over a broad temperature range, which makes them attractive for improved solid-state energy conversion devices

Inhibition of kinase IKK β suppresses cellular abnormalities induced by the human papillomavirus oncoprotein HPV 18E6

Human papillomavirus (HPV) is the leading cause of cervical cancer and has been implicated in several other cancer types including vaginal, vulvar, penile, and oropharyngeal cancers. Despite the recent availability of a vaccine, there are still over 310,000 deaths each year worldwide. Current treatments for HPV-mediated cancers show limited efficacy, and would benefit from improved understanding of disease mechanisms. Recently, we developed a Drosophila ‘HPV 18 E6’ model that displayed loss of cellular morphology and polarity, junctional disorganization, and degradation of the major E6 target Magi; we further provided evidence that mechanisms underlying HPV E6-induced cellular abnormalities are conserved between humans and flies. Here, we report a functional genetic screen of the Drosophila kinome that identified IKKβ—a regulator of NF-κB—as an enhancer of E6-induced cellular defects. We demonstrate that inhibition of IKKβ reduces Magi degradation and that this effect correlates with hyperphosphorylation of E6. Further, the reduction in IKKβ suppressed the cellular transformation caused by the cooperative action of HPVE6 and the oncogenic Ras. Finally, we demonstrate that the interaction between IKKβ and E6 is conserved in human cells: inhibition of IKKβ blocked the growth of cervical cancer cells, suggesting that IKKβ may serve as a novel therapeutic target for HPV-mediated cancers

Theory of Pseudomodes in Quantum Optical Processes

This paper deals with non-Markovian behaviour in atomic systems coupled to a structured reservoir of quantum EM field modes, with particular relevance to atoms interacting with the field in high Q cavities or photonic band gap materials. In cases such as the former, we show that the pseudo mode theory for single quantum reservoir excitations can be obtained by applying the Fano diagonalisation method to a system in which the atomic transitions are coupled to a discrete set of (cavity) quasimodes, which in turn are coupled to a continuum set of (external) quasimodes with slowly varying coupling constants and continuum mode density. Each pseudomode can be identified with a discrete quasimode, which gives structure to the actual reservoir of true modes via the expressions for the equivalent atom-true mode coupling constants. The quasimode theory enables cases of multiple excitation of the reservoir to now be treated via Markovian master equations for the atom-discrete quasimode system. Applications of the theory to one, two and many discrete quasimodes are made. For a simple photonic band gap model, where the reservoir structure is associated with the true mode density rather than the coupling constants, the single quantum excitation case appears to be equivalent to a case with two discrete quasimodes