Universal penalized regression (Elastic-net) model with differentially methylated promoters for oral cancer prediction.

BACKGROUND: DNA methylation showed notable potential to act as a diagnostic marker in many cancers. Many studies proposed DNA methylation biomarker in OSCC detection, while most of these studies are limited to specific cohorts or geographical location. However, the generalizability of DNA methylation as a diagnostic marker in oral cancer across different geographical locations is yet to be investigated. METHODS: We used genome-wide methylation data from 384 oral cavity cancer and normal tissues from TCGA HNSCC and eastern India. The common differentially methylated CpGs in these two cohorts were used to develop an Elastic-net model that can be used for the diagnosis of OSCC. The model was validated using 812 HNSCC and normal samples from different anatomical sites of oral cavity from seven countries. Droplet Digital PCR of methyl-sensitive restriction enzyme digested DNA (ddMSRE) was used for quantification of methylation and validation of the model with 22 OSCC and 22 contralateral normal samples. Additionally, pyrosequencing was used to validate the model using 46 OSCC and 25 adjacent normal and 21 contralateral normal tissue samples. RESULTS: With ddMSRE, our model showed 91% sensitivity, 100% specificity, and 95% accuracy in classifying OSCC from the contralateral normal tissues. Validation of the model with pyrosequencing also showed 96% sensitivity, 91% specificity, and 93% accuracy for classifying the OSCC from contralateral normal samples, while in case of adjacent normal samples we found similar sensitivity but with 20% specificity, suggesting the presence of early disease methylation signature at the adjacent normal samples. Methylation array data of HNSCC and normal tissues from different geographical locations and different anatomical sites showed comparable sensitivity, specificity, and accuracy in detecting oral cavity cancer with across. Similar results were also observed for different stages of oral cavity cancer. CONCLUSIONS: Our model identified crucial genomic regions affected by DNA methylation in OSCC and showed similar accuracy in detecting oral cancer across different geographical locations. The high specificity of this model in classifying contralateral normal samples from the oral cancer compared to the adjacent normal samples suggested applicability of the model in early detection.

Enhanced control over size, areal density, and shape of substrate-supported Au and Ag nanoparticles by solid-state dewetting and alloying.

The ability to manipulate the dimensions, areal density, and form of substrate-supported Au and Ag nanoparticles (NPs) is highly desirable for utilizing their plasmonic properties in biosensing, photovoltaics, and nanophotonic applications. The transformation of thin films into the substrate-supported nanostructures by solid-state dewetting (SSD), provides an avenue to manipulate the dimensional aspects of nanostructures simply and cost-effectively on a large scale. However, spontaneous agglomeration of the film produces randomly distributed and non-uniform nanostructures that must be controlled. Here, we have systematically studied the effect of annealing temperature, between 200 °C and 750 °C, on the dewetting morphology evolution of Au, Ag, and Au-Ag bilayer ultrathin films sputter deposited on thec-plane (0001) sapphire substrates. Regardless of the film thickness, Ag films dewet faster than Au films and produce spherical NPs, compared to faceted Au NPs, with broader size distribution. Whereas, by the SSD of Au-Ag bilayer ultrathin films, highly spherical and monodisperse AuAg bimetallic NPs can be fabricated. Furthermore, we have shown the possibility of fabricating the AuAg bimetallic NPs of varying compositions by adjusting the thickness of individual layers, thus enabling us to smoothly tune the spectral location of plasmonic resonance within the visible range.

Evolution and co-evolution: insights into the divergence of plant heat shock factor genes.

The Heat Shock Factor (Hsf) genes are widely distributed across the plant kingdom regulating the plant response to various abiotic stresses. In addition to natural selection, breeding and accelerated selection changed the structure and function of Hsf genes. 1076 Hsf genes from 30 genera from primitive algae to the most advanced plant species and major crop plants were used for phylogenetic analysis. The interspecific divergence was studied with 11 members of genus Oryza while intraspecific divergence was studied with sesame pan-genome adapted to diverse ecological niches. B2 genes in eudicots and monocots originated separately while A1 gave rise to the recently evolved Class-C genes and land colonization happened with evolution of A1 genes. An increase in the number of lineages in the Oryza clade with the evolution of AA genome indicated independent domestication and positive selection was observed in > 53% of loci whereas the highly conserved homologues were under purifying selection. The paralogous genes under positive selection exhibited more domain changes for diversified function and increased fitness. A significant co-evolving cluster involving amino acids Phenylalanine, Lysine and Valine played crucial role in maintaining hydrophobic core along with highly conserved Tryptophan residues. A mutation of Glutamic acid to Glutamine was observed in A8 genes of Lamiales affecting protein solvency. Breeding resulted in accumulation of mutations reducing the hydrophobicity of proteins and a further reduction in protein aggregation. This study identify genome duplications, non-neutral selection and co-evolving residues as causing drastic changes in the conserved domain of Hsf proteins. Supplementary information: The online version contains supplementary material available at 10.1007/s12298-022-01183-7.

Effect of Mo and space holder content on microstructure, mechanical and corrosion properties in Ti6AlxMo based alloy for bone implant.

The porous alloys of Ti6Al(3-15)Mo were developed to replace the fractured bone; the alloy consists of 6 wt% of Al which was taken as α the phase stabilizer and (3-15) wt% Mo with an increment of 3 wt% was taken as ß phase stabilizer. The porosity of these fabricated porous alloys was controlled by adjusting volume% of the ammonium bicarbonate (SH). These porous samples were characterized in terms of their microstructure, compressive strength, elastic modulus, energy absorption, ion release and corrosion rate in simulated body fluid (SBF) and these properties are compared with the existing alloys and human bone. The fabricated porous samples were characterized, and the obtained results were analysed as a function of Mo concentration and the volume% of space holder content. Three phases were found in the microstructure: α, α2 and ß phase of titanium. Increase in Mo content from 3 to 15 wt% has increased the volume fraction of ß phase from 7.45% to 64.09% and Kirkendall pores also are observed to be increased with increase in Mo content. α and α2 phase was differentiated by the TEM and phase map of EBSD images. The plateau stress, elastic modulus and energy absorption are observed to be decreased, and the densification strain is observed to be increased with the addition of Mo and SH content. The released ion concentration and corrosion rate are far below the tolerance limits of Ti, Al and Mo elements, in the static immersion test conducted in SBF solution.

Candidate screening of blast resistance donors for rice breeding.

Rice blast is one of the most serious diseases in the world. The use of resistant cultivars is the most preferred means to control this disease. Resistance often breaks down due to emergence of new races; hence identification of novel resistance donors is indispensable. In this study, a panel of 80 released varieties from National Rice Research Institute, Cuttack was genotyped with 36 molecular markers that were linked to 36 different blast resistance genes, to investigate the varietal genetic diversity and molecular marker-trait association with blast resistance. The polymorphism information content of 36 loci varied from 0.11 to 0.37 with an average of 0.34. The cluster analysis and population structure categorized the 80 National Rice Research Institute released varieties (NRVs) into three major genetic groups. The principal co-ordinate analysis displays the distribution of resistant and moderately resistant NRVs into different groups. Analysis of molecular variance result demonstrated maximum (97%) diversity within populations and minimum (3%) diversity between populations. Among tested markers, two markers (RM7364 and pi21_79-3) corresponding to the blast resistance genes (Pi56(t) and pi21) were significantly associated and explained a phenotypic variance of 4.9 to 5.1% with the blast resistance. These associated genes could be introgressed through marker-assisted to develop durable blast resistant rice varieties. The selected resistant NRVs could be good donors for the blast resistance in rice crop improvement research.

Correction: Blast resistance in Indian rice landraces: Genetic dissection by gene specific markers.

[This corrects the article DOI: 10.1371/journal.pone.0211061.].

Antibacterial and cytocompatibility study of modified Ti6Al4V surfaces through thermal annealing.

Silver coating of different thicknesses ranging from 5 to 20 nm was deposited on the Ti6Al4V substrate using DC sputtering followed by thermal annealing at 750 °C for 15 min in an ambient environment. The surface topography and elemental composition of annealed samples were analyzed using different characterization techniques. The silver ions (Ag+) concentration released from the modified titanium surface was calculated through inductive coupled plasma mass spectroscopy (ICP-MS). The plate counting method was used to quantify the bacteria-killing potential of modified titanium surface against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Fluoroquinolones-resistant Salmonella typhi (FRST) and Methicillin-resistant Staphylococcus aureus (MRSA) bacteria. The cell membrane integrity study of E. coli and S. aureus bacterium was done qualitatively using scanning electron microscopy and further confirmed with fluorescence microscopy. Due to thermal annealing, polygonal shaped oxide nanoparticles were formed on the titanium substrate. Moreover, the surface topography of modified titanium surface changes with the thickness of the silver film. In order to check the cytotoxic effect of modified titanium surface, mouse fibroblast cells (NIH3T3) were used for 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide (MTT) assay. The limited (<35 ppb) Ag+ ion release was noticed for 15 nm silver film which has shown the good bactericidal property and significant growth of fibroblast cells. This study proposes a simple and efficient method to enhance the antibacterial property of Ti6Al4V surfaces to avoid implant-related infection.

Blast resistance in Indian rice landraces: Genetic dissection by gene specific markers.

Understanding of genetic diversity is important to explore existing gene in any crop breeding program. Most of the diversity preserved in the landraces which are well-known reservoirs of important traits for biotic and abiotic stresses. In the present study, the genetic diversity at twenty-four most significant blast resistance gene loci using twenty-eight gene specific markers were investigated in landraces originated from nine diverse rice ecologies of India. Based on phenotypic evaluation, landraces were classified into three distinct groups: highly resistant (21), moderately resistant (70) and susceptible (70). The landraces harbour a range of five to nineteen genes representing blast resistance allele with the frequency varied from 4.96% to 100%. The cluster analysis grouped entire 161 landraces into two major groups. Population structure along with other parameters was also analyzed to understand the evolution of blast resistance gene in rice. The population structure analysis and principal coordinate analysis classified the landraces into two sub-populations. Analysis of molecular variance showed maximum (93%) diversity within the population and least (7%) between populations. Five markers viz; K3957, Pikh, Pi2-i, RM212and RM302 were strongly associated with blast disease with the phenotypic variance of 1.4% to 7.6%. These resistant landraces will serve as a valuable genetic resource for future genomic studies, host-pathogen interaction, identification of novel R genes and rice improvement strategies.

Abscopal effect of low-LET γ-radiation mediated through Rel protein signal transduction in a mouse model of nontargeted radiation response.

Ascertaining the ionizing radiation (IR)-induced bystander response and its preceding molecular regulation would increase our understanding of the mechanism of acute and delayed radiobiological effects. Recent evidence clearly prompted that radiation-induced nuclear factor kappa B (NF-κB) would play a key role in bystander responses in nontargeted cells. Accordingly, we investigated the orchestration of NF-κB signaling after IR in a nontargeted distant organ. Heart tissues from C57/BL6 mice either mock irradiated or exposed (limited to lower abdomen 1 cm diameter) to single-dose IR (SDR: 2 or 10 Gy) or fractionated IR (FIR, 2 Gy per day for 5 days) were examined for onset of abscopal NF-κB signal transduction, translated activity, downstream functional signaling and associated DNA damage. Radiation significantly induced NF-κB DNA binding activity in nontargeted heart. Transcriptional profiling showed that 51, 46 and 26 of 88 genes were significantly upregulated after 2 Gy, 10 Gy and FIR. Of these genes, 22 showed dose- and fractionation-independent upregulation. Immunohistochemistry revealed a robust increase in p65 and cMyc expression in distant heart after SDR and FIR. Immunoblotting revealed increased phosphorylation of p38 after 2 Gy and extracellular signal-regulated kinases 1/2 after 10 Gy in nontargeted heart. In addition, IR exposure significantly enhanced DNA fragmentation in nontargeted heart. Together, these data clearly indicated an induced abscopal response in distant organ after clinically relevant IR doses. More importantly, the results imply that orchestration of NF-κB signal transduction in nontargeted tissues may serve as an effector and could play a key role in induced abscopal responses.