Search Results (4)

Cancer cohorts are now known to be associated with increased rates of clonal hematopoiesis (CH). We sort to characterize the hematopoietic compartment of patients with melanoma and non-small cell lung cancer (NSCLC) given our recent population level analysis reporting evolving rates of secondary leukemias. The advent of immune checkpoint blockade (ICB) has dramatically changed our understanding of cancer biology and has altered the standards of care for patients. However, the impact of ICB on hematopoietic myeloid clonal expansion remains to be determined. We studied if exposure to ICB therapy affects hematopoietic clonal architecture and if their evolution contributed to altered hematopoiesis. Blood samples from patients with melanoma and NSCLC (n = 142) demonstrated a high prevalence of CH. Serial samples (or post ICB exposure samples; n = 25) were evaluated in melanoma and NSCLC patients. Error-corrected sequencing of a targeted panel of genes recurrently mutated in CH was performed on peripheral blood genomic DNA. In serial sample analysis, we observed that mutations in DNMT3A and TET2 increased in size with longer ICB exposures in the melanoma cohort. We also noted that patients with larger size DNMT3A mutations with further post ICB clone size expansion had longer durations of ICB exposure. All serial samples in this cohort showed a statistically significant change in VAF from baseline. In the serial sample analysis of NSCLC patients, we observed similar epigenetic expansion, although not statistically significant. Our study generates a hypothesis for two important questions: (a) Can DNMT3A or TET2 CH serve as predictors of a response to ICB therapy and serve as a novel biomarker of response to ICB therapy? (b) As ICB-exposed patients continue to live longer, the myeloid clonal expansion may portend an increased risk for subsequent myeloid malignancy development. Until now, the selective pressure of ICB/T-cell activating therapies on hematopoietic stem cells were less known and we report preliminary evidence of clonal expansion in epigenetic modifier genes (also referred to as inflammatory CH genes). Full article

This in vitro research aimed to evaluate the Tensile Bond Strength of Poly Ether Ether Ketone and Zirconia copings using resin cement with or without Visio.link adhesive. From commercially available Zirconia and PEEK, blocks were machined milled using (CAD)/(CAM) to obtain 20 Zirconia and 20 PEEK copings. These specimens were sandblasted using 110 μm of alumina. The two main groups (20 Zirconia and 20 PEEK copings) were divided further into 4 subgroups, GROUP 1 (n = 10) PEEK substructure with self-adhesive resin cement without pretreatment, and GROUP 2 (n = 10) PEEK substructure with self-adhesive resin cement pre-treated with Visio.link adhesive. GROUP 3 (n = 10) Zirconia copings with self-adhesive resin cement without pretreatment. GROUP 4 (n = 10) Zirconia copings with self-adhesive resin cement pre-treated with Visio.link adhesive. Universal testing machine was used to evaluate the tensile bond strength of these copings. The results were analyzed using SPSS software Version 25.0 (SPSS Inc., Chicago, IL, USA). One-way ANOVA and independent t-test were used to compare the mean scores. Statistically significant increase was observed in Tensile Bond Strength of samples when Visio.link adhesive was used. Tensile Bond Strength of PEEK copings and Zirconia copings with Visio.link adhesive is considerably greater than PEEK copings and Zirconia copings without adhesive. The mean Tensile Bond Strength of Zirconia (with or without adhesive) is less as compared to Tensile Bond Strength of PEEK (with or without adhesive), but the difference is not statistically significant. Full article

Rice is a global food grain crop for more than one-third of the human population and a source for food and nutritional security. Rice production is subjected to various stresses; blast disease caused by Magnaporthe oryzae is one of the major biotic stresses that has the potential to destroy total crop under severe conditions. In the present review, we discuss the importance of rice and blast disease in the present and future global context, genomics and molecular biology of blast pathogen and rice, and the molecular interplay between rice–M. oryzae interaction governed by different gene interaction models. We also elaborated in detail on M. oryzae effector and Avr genes, and the role of noncoding RNAs in disease development. Further, rice blast resistance QTLs; resistance (R) genes; and alleles identified, cloned, and characterized are discussed. We also discuss the utilization of QTLs and R genes for blast resistance through conventional breeding and transgenic approaches. Finally, we review the demonstrated examples and potential applications of the latest genome-editing tools in understanding and managing blast disease in rice. Full article

The history of DNA sequencing dates back to 1970s. During this period the two first generation nucleotide sequencing techniques were developed. Subsequently, Sanger's dideoxy method of sequencing gained popularity over Maxam and Gilbert's chemical method of sequencing. However, in the last decade, we have observed revolutionary changes in DNA sequencing technologies leading to the emergence of next-generation sequencing (NGS) techniques. NGS technologies have enhanced the throughput and speed of sequencing combined with bringing down the overall cost of the process over a time. The major applications of NGS technologies being genome sequencing and resequencing, transcriptomics, metagenomics in relation to plant-microbe interactions, exon and genome capturing, development of molecular markers and evolutionary studies. In this review, we present a broader picture of evolution of NGS tools, its various applications in crop plants, and future prospects of the technology for crop improvement. Full article