RNA, the earliest genetic and catalytic molecule, has a relatively delicate and labile chemical structure, when compared to DNA. It is prone to be damaged by alkali, heat, nucleases, or stress conditions. One mechanism to protect RNA or DNA from damage is through site-specific methylation. Here, we propose that RNA methylation began prior to DNA methylation in the early forms of life evolving on Earth. In this article, the biochemical properties of some RNA methyltransferases (MTases), such as 2′-O-MTases (Rlml/RlmN), spOUT MTases and the NSun2 MTases are dissected for the insight they provide on the transition from an RNA world to our present RNA/DNA/protein world.
More than 2 billion people are infected with helminth parasites across the globe. The burgeoning drug resistance against current anthelmintics in parasitic worms of humans and livestock requires urgent attention to tackle these recalcitrant worms. This review focuses on the advancements made in the area of helminth drug target discovery especially from the last few couple of decades. It highlights various approaches made in this field and enlists the potential drug targets currently being pursued to target economically important helminth species both from human as well as livestock to combat disease pathology of schistosomiasis, onchocerciasis, lymphatic filariasis, and other important macroparasitic diseases. Research in the helminths study is trending to identify potential and druggable targets through genomic, proteomic, biochemical, biophysical, in vitro experiments, and in vivo experiments in animal models. The availability of major helminths genome sequences and the subsequent availability of genome-scale functional datasets through in silico search and prioritization are expected to guide the experimental work necessary for target-based drug discovery. Organized and documented list of drug targets from various helminths of economic importance have been systematically covered in this review for further exploring their use and applications, which can give physicians and veterinarians effective drugs in hand to enable them control worm infections.
Development of a vaccine to prevent or reduce parasite development in lymphatic filariasis would be a complementary approach to existing chemotherapeutic tools. Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an attractive vaccine target due to its absence in mammals, prevalence in the major life stages of the parasite and immunoreactivity with human bancroftian antibodies, especially from endemic normal subjects. We have recently reported on the cloning, expression, purification and biochemical characterization of this vital enzyme of B. malayi. In the present study, immunoprophylactic evaluation of Bm-TPP was carried out against B. malayi larval challenge in a susceptible host Mastomys coucha and the protective ability of the recombinant protein was evaluated by observing the adverse effects on microfilarial density and adult worm establishment. Immunization caused 78.4% decrease in microfilaremia and 71.04% reduction in the adult worm establishment along with sterilization of 70.06% of the recovered live females. The recombinant protein elicited a mixed Th1/Th2 type of protective immune response as evidenced by the generation of both pro- and anti-inflammatory cytokines IL-2, IFN-γ, TNF-α, IL-4 and an increased production of antibody isotypes IgG1, IgG2a, IgG2b and IgA. Thus immunization with Bm-TPP conferred considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccine candidate against lymphatic filariasis (LF).
Discerning monozygotic twins, precisely predicting the age of human beings and most importantly interpreting human behavior remains a big challenge in forensic science. Modern advances in the field of epigenetics especially analysis of DNA methylation pattern can certainly help to identify and discriminate various single-source DNA samples such as bodily fluids collected from the crime scene. In this review, cytosine methylation analysis of DNA has been methodologically discussed with a broad range of applications in forensic science such as identifying single or mixed body fluid, discriminating monozygotic twins, age prediction, addiction/behavioral prediction as well as race/ethnicity identification. With the advances of next-generation sequencing techniques, blooming of DNA methylation datasets and together with standard epigenetic protocols, the prospect of investigating and solving these critical issues in forensic science is highly promising in the court of law.
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