LISTERIN E3 Ubiquitin Ligase and Ribosome-Associated Quality Control (RQC) Mechanism.

According to cellular demands, ribosomes synthesize and maintain the desired pool of proteins inside the cell. However, sometimes due to defects in ribosomal machinery and faulty mRNAs, these nascent polypeptides are constantly under threat to become non-functional. In such conditions, cells acquire the help of ribosome-associated quality control mechanisms (RQC) to eliminate such aberrant nascent proteins. The primary regulator of RQC is RING domain containing LISTERIN E3 ubiquitin ligase, which is associated with ribosomes and alleviates non-stop proteins-associated stress in cells. Mouse RING finger protein E3 ubiquitin ligase LISTERIN is crucial for embryonic development, and a loss in its function causes neurodegeneration. LISTERIN is overexpressed in the mouse brain and spinal cord regions, and its perturbed functions generate neurological and motor deficits, but the mechanism of the same is unclear. Overall, LISTERIN is crucial for brain health and brain development. The present article systematically describes the detailed nature, molecular functions, and cellular physiological characterization of LISTERIN E3 ubiquitin ligase. Improve comprehension of LISTERIN's neurological roles may uncover pathways linked with neurodegeneration, which in turn might elucidate a promising novel therapeutic intervention against human neurodegenerative diseases.

Non-interference of Bovine-Human reassortant pentavalent rotavirus vaccine ROTASIIL® with the immunogenicity of infant vaccines in comparison with a licensed rotavirus vaccine.

BACKGROUND: A newly developed bovine-human reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was tested for its potential effect on the immunogenicity of concomitantly administered EPI vaccines in infants in a randomized controlled study in India. METHODS: In this Phase III, multicenter, open label, randomized, controlled study, three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given to healthy infants at 6, 10, and 14 weeks of age. Subjects also received three doses of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell pertussis, hepatitis B, and haemophilus influenzae type b conjugate - pentavalent vaccine) and oral polio vaccine concomitantly at 6, 10, and 14 weeks of age and a single dose of inactivated polio vaccine at 14 weeks of age. Blood samples were collected four weeks after the final vaccination to assess immune responses to all the vaccines administered. For diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 antibodies, non-interference was to be supported if the lower limit of the two-sided 90% confidence interval (CI) for the seroprotection rate difference for the BRV-PV group minus the Rotarix® group was >10.0%. For pertussis antibodies, non-interference was to be supported if the lower limit of the two-sided 90% CI for the ratio of geometric mean concentrations (GMCs) was >0.5. RESULTS: A total of 1500 infants were randomized to either BRV-PV (1125 infants) or Rotarix® (375 infants), of which 1341 completed the study as per the protocol. More than 97% of subjects achieved seroprotective antibody titres against diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 in both groups. The difference in seroprotection rates between the BRV-PV group and the Rotarix® group for all these antibodies was less than 1%. The ratio of GMCs of anti-pertussis IgG concentrations for the BRV-PV group versus Rotarix® was 1.04 [90% CI: 0.90; 1.19]. CONCLUSION: BRV-PV does not interfere with the immunogenicity of concomitantly administered routine infants vaccines.

Comparison of diagnostic efficacy of umbilical artery and middle cerebral artery waveform with color Doppler study for detection of intrauterine growth restriction.

BACKGROUND AND OBJECTIVES: Intrauterine growth restriction is associated with increased perinatal mortality and morbidity, possibly extending also in adult life, as compared to fetuses and newborns presenting characteristics of normal growth. The present study had been planned to measure the pulsatility index (PI) and resistive index of the middle cerebral artery with pulsatility and resistive index of the umbilical artery in predicting fetal growth restriction. MATERIALS AND METHODS: A total of 60 pregnant women with a clinical history and grayscale-screened patients were taken for Doppler analysis, and a final comparison of accuracy of Doppler indices was done with perinatal outcome. STATISTICAL ANALYSIS: The statistical analysis was done using the Statistical Package for Social Sciences version 15.0 statistical analysis software. The values were represented in number (%) and mean ± SD. OBSERVATION AND RESULTS: The umbilical artery PI had maximum sensitivity at the third visit (32-37 weeks) and maximum specificity also at the third visit (32-37 weeks). The umbilical artery resistive index had maximum sensitivity at the second visit (28-32 weeks) and maximum specificity at the third visit (32-37 weeks). The MCA PI had an overall diagnostic accuracy of 52.8 %. CONCLUSION: The PI of the umbilical artery was more sensitive than the PI of the middle cerebral artery. Umbilical artery PI has the maximum overall diagnostic accuracy of 75 %.