RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and a novel mRNA decay pathway.

mRNA level is controlled by factors that mediate both mRNA synthesis and decay, including the 5' to 3' exonuclease Xrn1. Here we show that nucleocytoplasmic shuttling of several yeast mRNA decay factors plays a key role in determining both mRNA synthesis and decay. Shuttling is regulated by RNA-controlled binding of the karyopherin Kap120 to two nuclear localization sequences (NLSs) in Xrn1, location of one of which is conserved from yeast to human. The decaying RNA binds and masks NLS1, establishing a link between mRNA decay and Xrn1 shuttling. Preventing Xrn1 import, either by deleting KAP120 or mutating the two Xrn1 NLSs, compromises transcription and, unexpectedly, also cytoplasmic decay, uncovering a cytoplasmic decay pathway that initiates in the nucleus. Most mRNAs are degraded by both pathways - the ratio between them represents a full spectrum. Importantly, Xrn1 shuttling is required for proper responses to environmental changes, e.g., fluctuating temperatures, involving proper changes in mRNA abundance and in cell proliferation rate.

Bioleaching of copper from large printed circuit boards for synthesis of organic-inorganic hybrid.

The present study described a process for copper (Cu) bioleaching from waste printed circuit boards (PCBs). The 45 (± 0.18) mg/g Cu was found in waste PCBs. Acidiphilium acidophilum (NCIM 5344) (A. acidophilum) and hydrogen peroxide (H2O2) were used for two-step Cu bioleaching. A. acidophilum showed growth in 9K medium containing glucose and sulfur. During the growth the bacteria decreased medium pH from 3.5 (± 0.01) to 1.0 (± 0.02) in 10 days. The results showed that it required 2.5 h to leach all of the Cu from single PCB piece using 60 mL culture supernatant + 15 mL H2O2 at 60 °C temperature and static condition. The leached Cu was further used to synthesize the organic-inorganic hybrid (OIH). For this study, egg white was used as a polyphenol oxidase (PPO) enzyme source. The morphological, elemental, and structural analysis was carried out using scanning electron microscopy (SEM)-energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Further the PPO enzyme activity was tested in OIH and crude enzyme (egg white). The egg white showed 0.00014 (± 0.00001) U/mg/min PPO activity while OIH showed 0.005 (± 0.00016) U/mg/min PPO activity. The pH 7 and 30 °C temperature were found to be optimum for PPO enzyme activity. The OIH was applied for phenol degradation. It degraded 95 (± 0.49)% of phenol (5 mM). The efficiency of phenol degradation decreased with an increase in phenol concentration.

Identification and Assessment of Potential Drug-Drug Interactions in Intensive Care Unit Patients.

CONTEXT: Intensive care unit (ICU) patients suffer from various comorbidities and usually receive complex pharmacotherapy which increases the risk of drug-drug interactions (DDIs). AIM: To identify and assess potential DDIs (pDDIs) in ICU patients. SETTINGS AND DESIGN: A prospective observational study conducted in ICU of a tertiary care hospital for a period of 6 months. MATERIALS AND METHODS: Patient information was noted in the data collection form and pDDIs were assessed using Micromedex®database. STATISTICAL ANALYSIS USED: Chi-square test was used to find correlation of pDDIs with patient parameters. p value was calculated keeping the significance level 0.05. RESULTS: Total 400 subjects were included; having an average age of 55.99 ± 15.62 years with a higher percentage of males (61.75%). About 305 (76.25%) patients were found with pDDIs, showing an average of 2.93 pDDIs/patient. The findings of this study were as follows: Total interactions = 1171, contraindicated = 6 (1%), major = 715 (61%), moderate = 428 (36%), and minor = 22 (2%) pDDIs. Further, majority of pDDIs had onset of action "not specified" documentation "fair" and probable mechanism "pharmacodynamic" in nature. Significant association of occurrence of pDDIs was found with number of drugs prescribed to patients in ICU. CONCLUSION: This study demonstrated a high prevalence of pDDI in ICU due to the complexity of pharmacotherapy which showed major pDDIs as the most evident (61%) while contraindicated were 1%. Further studies are needed to better explore this area which may help in realizing the goal of good clinical practice and may offer a methodology to further increase drug safety. KEY MESSAGES: "Monitoring and assessment of DDIs is needed for better patient care". HOW TO CITE THIS ARTICLE: Wagh BR, Godbole DD, et al. Identification and Assessment of Potential Drug-Drug Interactions in Intensive Care Unit Patients. Indian J Crit Care Med 2019;23(4):170-174.