Semantically assessing the reliability of protein interactions

Protein–protein interactions (PPIs) play very important roles in many cellular processes, and provide rich information for discovering biological facts and knowledge. Although various experimental approaches have been developed to generate large amounts of PPI data for different organisms, high-throughput experimental data usually suffers from high error rates, and as a consequence, the biological knowledge discovered from this data is distorted or incorrect. Therefore, it is vital to assess the quality of protein interaction data and extract reliable protein interactions from the high-throughput experimental data. In this paper, we propose a new Semantic Reliability (SR) method to assess the reliability of each protein interaction and identify potential false-positive protein interactions in a dataset. For each pair of target interacting proteins, the SR method takes into account the semantic influence between proteins that interact with the target proteins, and the semantic influence between the target proteins themselves when assessing the interaction reliability. Evaluations on real protein interaction datasets demonstrated that our method outperformed other existing methods in terms of extracting more reliable interactions from original protein interaction datasets.     

Pyrazolopyrimidinone Based Selective Inhibitors of PDE5 for the Treatment of Erectile Dysfunction

Continuing research with our earlier finding of sildenafil based analogs in the search of new inhibitors of PDE5 for erectile dysfunction suggested that there is a scope of modifications at N-methylpiperazine ring with hydrophobic region followed by hydrogen bond donor or acceptor region. However, the leads identified earlier had some limitations like poor pharmacokinetic (PK) profile, low aqueous solubility and poor bioavailability. In this direction, a new series of sildenafil based analogs were designed, synthesized and screened for their PDE5 inhibitory activity. In this series compound 18 was found to have excellent in vitro activity with selectivity towards PDE5 isozyme, also the in vivo activity and pharmacokinetic profile was excellent. The cyp inhibition and CaCO₂ permeability was also excellent for compound 18 .     

Monitoring of microbial proteome dynamics using Raman stable isotope probing

Abnormal protein kinetics could be a cause of several diseases associated with essential life processes. An accurate understanding of protein dynamics and turnover is essential for developing diagnostic or therapeutic tools to monitor these changes. Raman spectroscopy in combination with stable isotope probes (SIP) such as carbon-13, and deuterium has been a breakthrough in the qualitative and quantitative study of various metabolites. In this work, we are reporting the utility of Raman-SIP for monitoring dynamic changes in the proteome at the community level. We have used ¹³C-labeled glucose as the only carbon source in the medium and verified its incorporation in the microbial biomass in a time-dependent manner. A visible redshift in the Raman spectral vibrations of major biomolecules such as nucleic acids, phenylalanine, tyrosine, amide I, and amide III were observed. Temporal changes in the intensity of these bands demonstrating the feasibility of protein turnover monitoring were also verified. Kanamycin, a protein synthesis inhibitor was used to assess the feasibility of identifying effects on protein turnover in the cells. Successful application of this work can provide an alternate/adjunct tool for monitoring proteome-level changes in an objective and nondestructive manner.     

Housing environment and early childhood development in sub-Saharan Africa: A cross-sectional analysis

BackgroundThe influence of the safety and security of environments on early childhood development (ECD) has been under-explored. Although housing might be linked to ECD by affecting a child’s health and a parent’s ability to provide adequate care, only a few studies have examined this factor. We hypothesized that housing environment is associated with ECD in sub-Saharan Africa (SSA).Methods and findingsFrom 92,433 children aged 36 to 59 months who participated in Multiple Indicator Cluster Survey (MICS) in 20 SSA countries, 88,271 were tested for cognitive and social–emotional development using the Early Childhood Development Index (ECDI) questionnaire and were thus included in this cross-sectional analysis. Children’s mean age was 47.2 months, and 49.8% were girls. Children were considered developmentally on track in a certain domain if they failed no more than 1 ECDI item in that domain. In each country, we used conditional logistic regression models to estimate the association between improved housing (housing with finished building materials, improved drinking water, improved sanitation facilities, and sufficient living area) and children’s cognitive and social–emotional development, accounting for contextual effects and socioeconomic factors. Estimates from each country were pooled using random-effects meta-analyses. Subgroup analyses were conducted by the child’s gender, maternal education, and household wealth quintiles. On-track cognitive development was associated with improved housing (odds ratio [OR] = 1.15, 95% CI 1.06 to 1.24, p < 0.001), improved drinking water (OR = 1.07, 95% CI 1.00 to 1.14, p = 0.046), improved sanitation facilities (OR = 1.15, 95% CI 1.03 to 1.28, p = 0.014), and sufficient living area (OR = 1.06, 95% CI 1.01 to 1.10, p = 0.018). On-track social–emotional development was associated with improved housing only in girls (OR = 1.14, 95% CI 1.04 to 1.25, p = 0.006). The main limitations of this study included the cross-sectional nature of the datasets and the use of the ECDI, which lacks sensitivity to measure ECD outcomes.ConclusionsIn this study, we observed that improved housing was associated with on-track cognitive development and with on-track social–emotional development in girls. These findings suggest that housing improvement in SSA may be associated not only with benefits for children’s physical health but also with broader aspects of healthy child development.

In a cross-sectional analysis of nationally representative survey data from 20 countries, Yaqing Gao and colleagues investigate associations between housing environment and cognitive and social development in children.