MiR-24 Tumor Suppressor Activity Is Regulated Independent of p53 and through a Target Site Polymorphism

MicroRNAs (miRNAs) are predicted to regulate approximately 30% of all human genes; however, only a few miRNAs have been assigned their targets and specific functions. Here we demonstrate that miR-24, a ubiquitously expressed miRNA, has an anti-proliferative effect independent of p53 function. Cell lines with differential p53 status were used as a model to study the effects of miR-24 on cell proliferation, cell cycle control, gene regulation and cellular transformation. Overexpression of miR-24 in six different cell lines, independent of p53 function, inhibited cell proliferation and resulted in G2/S cell cycle arrest. MiR-24 over expression in cells with wt-p53 upregulated TP53 and p21 protein; however, in p53-null cells miR-24 still induced cell cycle arrest without the involvement of p21. We show that miR-24 regulates p53-independent cellular proliferation by regulating an S-phase enzyme, dihydrofolate reductase (DHFR) a target of the chemotherapeutic drug methotrexate (MTX). Of interest, we found that a miR-24 target site polymorphism in DHFR 3′ UTR that results in loss of miR-24-function and high DHFR levels in the cell imparts a growth advantage to immortalized cells and induces neoplastic transformation. Of clinical significance, we found that miR-24 is deregulated in human colorectal cancer tumors and a subset of tumors has reduced levels of miR-24. A novel function for miR-24 as a p53-independent cell cycle inhibitory miRNA is proposed

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Translational Modulation of Proteins Expressed from Bicistronic Vectors

Bicistronic vectors are useful tools for exogenous expression of two gene products from a single promoter element; however, reduced expression of protein from the second cistron compared with the first cistron is a common limitation to this approach. To overcome this limitation, we explored use of dihydrofolate reductase (DHFR) complementary DNA encoded in bicistronic vectors to induce a second protein of interest by methotrexate (MTX) treatment. Previous studies have demonstrated that levels of DHFR protein and DHFR fusion protein can be induced translationally following MTX treatment of cells. We demonstrated that in response to MTX treatment, DHFR partner protein in a bicistronic construct is induced for longer periods of time when compared with endogenous DHFR and DHFR fusion protein, in vitro and in vivo. Using rapamycin pretreatment followed by MTX treatment, we also devised a strategy to modulate levels of two proteins expressed from a bicistronic construct in a cap-independent manner. To our knowledge, this is the first report demonstrating that levels of proteins in DHFR-based bicistronic constructs can be induced and modulated using MTX and rapamycin treatment

WALOP-South: A wide-field one-shot linear optical polarimeter for PASIPHAE survey

WALOP (Wide-Area Linear Optical Polarimeter)-South, to be mounted on the 1m SAAO telescope in South Africa, is first of the two WALOP instruments currently under development for carrying out the PASIPHAE survey. Scheduled for commissioning in the year 2021, the WALOP instruments will be used to measure the linear polarization of around 106 stars in the SDSS-r broadband with 0.1 % polarimetric accuracy, covering 4000 square degrees in the Galactic polar regions. The combined capabilities of one-shot linear polarimetry, high polarimetric accuracy (< 0.1 %) and polarimetric sensitivity (< 0.05 %), and a large field of view (FOV) of 35 35 arcminutes make WALOP-South a unique astronomical instrument. In a single exposure, it is designed to measure the Stokes parameters I, q and u in the SDSS-r broadband and narrowband filters between 500-700 nm. During each measurement, four images of the full field corresponding to the polarization angles of 0°, 45°, 90° and 135° will be imaged on four detectors and carrying out differential photometry on these images will yield the Stokes parameters. Major challenges in designing WALOP-South instrument include- (a) in the optical design, correcting for the spectral dispersion introduced by large split angle Wollaston Prisms used as polarization analyzers as well as aberrations from the wide field, and (b) making an optomechanical design adherent to the tolerances required to obtain good imaging and polarimetric performance under all temperature conditions as well as telescope pointing positions. We present the optical and optomechanical design for WALOP-South which overcomes these challenges

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Not AvailableSoils in the hot, arid topical regions are low in organic matter and fertility and are structurally poor. Consequently, these soils suffer on account of poor physical, chemical, and biological soil quality traits, leading to miserably low crop yields. Long-term use of conjunctive nutrient management and conservation tillage practices may have a profound effect on improving the quality of these soils. Therefore, the objective of this study was to identify the key soil quality indicators, indices, and the best soiland nutrient-management practices that can improve soil quality on long-term basis for enhanced productivity under a pearl millet–based system. The studies were conducted for the Hissar Centre of All-India Coordinated Research Project at the Central Research Institute for Dryland Agriculture, Hyderabad. Conjunctive nutrient-use treatments and conservation tillage significantly influenced the majority of the soil quality parameters in both the experiments. In experiment 1, the key soil quality indicators that significantly contributed to soil quality in a rainfed pearl millet–mung bean system were available nitrogen (N, 35%), available zinc (Zn; 35%), available copper (Cu; 10%), pH (10%), available potassium (K; 5%), and dehydrogenase assay (5%). The three best conjunctive nutrient-use treatments in terms of soil quality indices (SQI) were T3, 25 kg N (compost) (1.52) >T6, 15 kg N (compost) + 10 kg N (inorganic) + biofertilizer (1.49) >T5, 15 kg N (compost) + 10 kg N (green leaf manure) (1.47). In experiment 2, under a rainfed pearl millet system, the key indicators and their percentage contributions were electrical conductivity (15%), available N (19%), exchangeable magnesium (Mg; 18%), available manganese (Mn; 13%), dehydrogenase assay (19%), microbial biomass carbon (C; 5%), and bulk density (11%). The three best tillage +nutrient treatments identified from the viewpoint of soil quality were T1, conventional tillage (CT) + two intercultures (IC) + 100% N (organic source/compost) (1.74) >T3, CT + two IC + 100% N (inorganic source) (1.74) >T4, low tillage + two IC + 100% N (organic source/compost) (1.70). The findings of the present study as well as the state-of-the-art methodology adopted could be of much interest and use to the future researchers including students, land managers, state agricultural officers, growers/farmers, and all other associated stakeholders. The prediction function developed between long-term pearl millet crop yields (y) and soil quality indices (x) in this study could be of much use in predicting the crop yields with a given change in soil quality index under similar situations.Not Availabl