Type 2 diabetes mellitus (T2DM) is no more a lifestyle disease of developed countries. It has emerged as a major health problem worldwide including developing countries. However, how diabetes could be detected at an early stage (prediabetes) to prevent the progression of disease is still unclear. Currently used biomarkers like glycated hemoglobin and assessment of blood glucose level have their own limitations. These classical markers can be detected when the disease is already established. Prognosis of disease at early stages and prediction of population at a higher risk require identification of specific markers that are sensitive enough to be detected at early stages of disease. Biomarkers which could predict the risk of disease in people will be useful for developing preventive/proactive therapies to those individuals who are at a higher risk of developing the disease. Recent studies suggested that the expression of biomolecules including microRNAs, proteins, and metabolites specifically change during the progression of T2DM and related complications, suggestive of disease pathology. Owing to their omnipresence in body fluids and their association with onset, progression, and pathogenesis of T2DM, these biomolecules can be potential biomarker for prognosis, diagnosis, and management of disease. In this article, we summarize biomolecules that could be potential biomarkers and their signature changes associated with T2DM and related complications during disease pathogenesis.
Correct termination of protein synthesis would be a critical step in translation of organellar open reading frames (ORFs) of the apicoplast and mitochondrion of the malaria parasite. We identify release factors (RFs) responsible for recognition of the UAA and UGA stop-codons of apicoplast ORFs and the sole UAA stop-codon that terminates translation from the three mitochondrial ORFs. A single nuclear-encoded canonical RF2, PfRF2Api , localizes to the apicoplast. It has a conserved tripeptide motif (SPF) for stop-codon recognition and is sufficient for peptidyl-tRNA hydrolysis (PTH) from both UAA and UGA. Two RF family proteins are targeted to the parasite mitochondrion; a canonical RF1, PfRF1Mit , with a variant codon-recognition motif (PxN instead of the conserved RF1 PxT) is the major peptidyl-hydrolase with specific recognition of the UAA codon relevant to mitochondrial ORFs. Mutation of the N residue of the PfRF1Mit PxN motif and two other conserved residues of the codon recognition domain lowers PTH activity from pre-termination ribosomes indicating their role in codon-recognition. The second RF imported by the mitochondrion is the non-canonical PfICT1 that functions as a dimer and mediates codon nonspecific peptide release. Our results help delineate a critical step in organellar translation in Plasmodium, which is an important target for anti-malarials.
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