Outfitting COVID-19: An Effective Therapeutic Approach

Use of antisense oligonucleotides of the type 3'-(N)x-AAAUUUG-(N)x-5' against slippery sequence  and polynucleotides against pseudoknots forming sequences of SARS-CoV-2 RNA would block the first translation of ORF1a and ORF1b and hence dwindle the virus replication. It is easy to synthesize and deliver the antisense oligonucleotides to the target by directly injecting the nano formulation into the blood

Detecting galaxies in a large H{\sc i}~spectral cube

The upcoming Square Kilometer Array (SKA) is expected to produce humongous amount of data for undertaking H{\sc i}~science. We have developed an MPI-based {\sc Python} pipeline to deal with the large data efficiently with the present computational resources. Our pipeline divides such large H{\sc i}~21-cm spectral cubes into several small cubelets, and then processes them in parallel using publicly available H{\sc i}~source finder {\sc SoFiA-$2$}. The pipeline also takes care of sources at the boundaries of the cubelets and also filters out false and redundant detections. By comapring with the true source catalog, we find that the detection efficiency depends on the {\sc SoFiA-$2$} parameters such as the smoothing kernel size, linking length and threshold values. We find the optimal kernel size for all flux bins to be between $3$ to $5$ pixels and $7$ to $15$ pixels, respectively in the spatial and frequency directions. Comparing the recovered source parameters with the original values, we find that the output of {\sc SoFiA-$2$} is highly dependent on kernel sizes and a single choice of kernel is not sufficient for all types of H{\sc i}~galaxies. We also propose use of alternative methods to {\sc SoFiA-$2$} which can be used in our pipeline to find sources more robustly.Comment: 15 pages, 7 figures, Accepted for publication in the Special Issue of Journal of Astrophysics and Astronomy on "Indian Participation in the SKA'', comments are welcom

Monomeric and dimeric oxidomolybdenum(V and VI) complexes, cytotoxicity, and DNA interaction studies: molybdenum assisted C═N bond cleavage of salophen ligands

Four novel dimeric bis-μ-imido bridged metal–metal bonded oxidomolybdenum(V) complexes [MoV2O2L′21–4] (1–4) (where L′1–4 are rearranged ligands formed in situ from H2L1–4) and a new mononuclear dioxidomolybdenum(VI) complex [MoVIO2L5] (5) synthesized from salen type N2O2 ligands are reported. This rare series of imido- bridged complexes (1–4) have been furnished from rearranged H3L′1–4 ligands, containing an aromatic diimine (o-phenylenediamine) “linker”, where Mo assisted hydrolysis followed by −C═N bond cleavage of one of the arms of the ligand H2L1–4 took place. A monomeric molybdenum(V) intermediate species [MoVO(HL′1–4)(OEt)] (Id1–4) was generated in situ. The concomitant deprotonation and dimerization of two molybdenum(V) intermediate species (Id1–4) ultimately resulted in the formation of a bis-μ-imido bridge between the two molybdenum centers of [MoV2O2L′21–4] (1–4). The mechanism of formation of 1–4 has been discussed, and one of the rare intermediate monomeric molybdenum(V) species Id4 has been isolated in the solid state and characterized. The monomeric dioxidomolybdenum(VI) complex [MoVIO2L5] (5) was prepared from the ligand H2L5 where the aromatic “linker” was replaced by an aliphatic diimine (1,2-diaminopropane). All the ligands and complexes have been characterized by elemental analysis, IR, UV–vis spectroscopy, NMR, ESI- MS, and cyclic voltammetry, and the structural features of 1, 2, 4, and 5 have been solved by X-ray crystallography. The DNA binding and cleavage activity of 1–5 have been explored. The complexes interact with CT-DNA by the groove binding mode, and the binding constants range between 103 and 104 M–1. Fairly good photoinduced cleavage of pUC19 supercoiled plasmid DNA was exhibited by all the complexes, with 4 showing the most promising photoinduced DNA cleavage activity of ∼93%. Moreover, in vitro cytotoxic activity of all the complexes was evaluated by MTT assay, which reveals that the complexes induce cell death in MCF-7 (human breast adenocarcinoma) and HCT-15 (colon cancer) cell lines

Polyethylene/Polyhydroxyalkanoates-based Biocomposites and Bionanocomposites

The development of advanced polymer composite materials having superior mechanical properties has opened up new horizons in the field of science and engineering. Polyethylene (PE) is considered one of the most widely used thermoplastics in the world due to its excellent properties which have excellent chemical inertness, low coefficient of friction, toughness, near-zero moisture absorption, ease of processing and electrical properties. Polyhydroxyalkanoates (PHAs) are garnering increasing attention in the biodegradable polymer market because of their promising properties such as high biodegradability in different environments. This chapter covers polyethylene/polyhydroxyalkanoates-based biocomposites and bionanocomposites. It summarizes many of the recent research accomplishments in the area of PE/PHAs-based biocomposites and bionanocomposites such as state-of-the-art regarding different methods of their preparation. Also discussed are different characterization techniques and use of PE/PHAs-based biocomposites and bionanocomposites in biomedical, packaging, structural, military, coating, fire retardant, aerospace and optical applications, along with recycling and lifetime studies

DNA methylation regulates Microtubule-associated tumor suppressor 1 in human non-small cell lung carcinoma

Microtubule associated tumor suppressor 1 (MTUS1) has been recognized as a tumor suppressor gene in multiple cancers. However, the molecular mechanisms underlying the regulation of MTUS1 are yet to be investigated. This study aimed to clarify the significance of DNA methylation in silencing MTUS1 expression. We report that MTUS1 acts as tumor suppressor in non-small cell lung carcinoma (NSCLC). Analysis of in silica database and subsequent knockdown of DNMT1 suggested an inverse correlation between DNMT1 and mars]. function. Interestingly, increased methylation at MTUS1 promoter is associated with low expression of MTUS1. Treatment with DNA methyltransferases (DNMTs) inhibitor, 5-aza-2'-deoxycytidine (AZA) leads to both reduced promoter methylation accompanied with enrichment of H3K9Ac and enhanced MTUS1 expression. Remarkably, knockdown of MTUS1 showed increased proliferation and migration of NSCLC cells in contrast to diminished proliferation and migration, upon treatment with AZA. We concluded that low expression of MTUS1 correlates to DNA methylation and histone deacetylation in human NSCLC

Epigenetic silencing of genes enhanced by collective role of reactive oxygen species and MAPK signaling downstream ERK/Snail axis: Ectopic application of hydrogen peroxide repress CDH1 gene by enhanced DNA methyltransferase activity in human breast cancer

Loss of E-cadherin and epithelial to mesenchymal transition (EMT) are key steps in cancer progression. Reactive oxygen species (ROS) play significant roles in cellular physiology and homeostasis. Roles of E-cadherin (CDH1), EMT and ROS are intriguingly illustrated in many cancers without focusing their collective concert during cancer progression. We report that hydrogen peroxide (H2O2) treatment modulate CDH1 gene expression by epigenetic modification(s). Sublethal dosage of H2O2 treatment decrease E-cadherin, increase DNMT1, HDAC1, Snail, Slug and enrich H3K9me3 and H3K27me3 in the CDH1 promoter. The effect of H2O2 was attenuated by ROS scavengers; NAC, lupeol and beta-sitosterol. DNMT inhibitor, AZA prevented the H2O2 induced promoter-CpG-island methylation of CDH1. Treatment of cells with U0126 (inhibitor of ERK) reduced the expression of DNMT1, Snail and Slug, increased CDHL This implicates that CDH1 is synergistically repressed by histone methylation, DNA methylation and histone deacetylation mediated chromatin remodelling and activation of Snail and Slug through ERK pathway. Increased ROS leads to activation of epigenetic machineries and EMT activators Snail/Slug which in their course of action inactivates CDH1 gene and lack of E-cadherin protein promotes EMT in breast cancer cells. ROS and ERK signaling facilitate epigenetic silencing and support the fact that subtle increase of ROS above basal level act as key cell signaling molecules. Free radical scavengers, lupeol and beta-sitosterol may be tested for therapeutic intervention of breast cancer. This work broadens the amplitude of epigenome and open avenues for investigations on conjoint effects of canonical and intrinsic metabolite signaling and epigenetic modulations in cancer

Autophagy: cancer’s friend or foe?

The functional relevance of autophagy in tumor formation and progression remains controversial. Autophagy can promote tumor suppression during cancer initiation and protect tumors during progression. Autophagy-associated cell death may act as a tumor suppressor, with several autophagy-related genes deleted in cancers. Loss of autophagy induces genomic instability and necrosis with inflammation in mouse tumor models. Conversely, autophagy enhances survival of tumor cells subjected to metabolic stress and may promote metastasis by enhancing tumor cell survival under environmental stress. Unraveling the complex molecular regulation and multiple diverse roles of autophagy is pivotal in guiding development of rational and novel cancer therapies