Albrightcannon4630

Biomolecules undergo liquid-liquid phase separation (LLPS), resulting in the formation of multicomponent protein-RNA membraneless organelles in cells. However, the physiological and pathological role of post-translational modifications (PTMs) on the biophysics of phase behavior is only beginning to be probed. To study the effect of PTMs on LLPS in silico, we extend our transferable coarse-grained model of intrinsically disordered proteins to include phosphorylated and acetylated amino acids. Using the parameters for modified amino acids available for fixed-charge atomistic force fields, we parameterize the size and atomistic hydropathy of the coarse-grained-modified amino acid beads and, hence, the interactions between the modified and natural amino acids. We then elucidate how the number and position of phosphorylated and acetylated residues alter the protein's single-chain compactness and its propensity to phase separate. We show that both the number and the position of phosphorylated threonines/serines or acetylated lysines can serve as a molecular on/off switch for phase separation in the well-studied disordered regions of Fused in Sarcoma (FUS) and DDX3X, respectively. We also compare modified residues to their commonly used PTM mimics for their impact on chain properties. Importantly, we show that the model can predict and capture experimentally measured differences in the phase behavior for position-specific modifications, showing that the position of modifications can dictate phase separation. In sum, this model will be useful for studying LLPS of post-translationally modified intrinsically disordered proteins and predicting how modifications control phase behavior with position-specific resolution.

Microbial exposures in early childhood direct the development of the immune system and their diversity may influence the risk of allergy development. We aimed to determine whether the indoor microbial diversity at early-life is associated with the development of allergic rhinitis and inhalant atopy.

The study population included children within two birth cohorts Finnish rural-suburban LUKAS (N=312), and German urban LISA from Munich and Leipzig study centers (N=248). The indoor microbiota diversity (Chao1 richness and Shannon entropy) was characterized from floor dust samples collected at the child age of 2-3 months by Illumina MiSeq sequencing of bacterial and fungal DNA amplicons. Allergic rhinitis and inhalant atopy were determined at the age of 10 years and analyzed using logistic regression models.

High bacterial richness (aOR 0.19, 95%CI 0.09-0.42 for middle and aOR 0.12, 95%CI 0.05-0.29 for highest vs. lowest tertile) and Shannon entropy were associated with lower risk of allergic rhinitis in LISlts between two differing cohorts - suggests that specific constituents of the diversity may be relevant.Microalgal cultivation in municipal wastewater treatment plants (WWTPs) can realize the coupling of wastewater treatment and microalgae energy utilization, however, the residual antibiotics in effluents from WWTPs affect the growth of microalgae. In this study, green alga (Scenedesmus obliquus) cells were inoculated into the effluents to ascertain the attenuation pathways of erythromycin (ERY) and the biochemical responses of microalga in a microalga-effluent system. Results showed that hydrolysis, photolysis, and biodegradation (including bioadsorption) cause the attenuation of ERY in a microalga-effluent system, and the biodegradation (including bioadsorption) has the greatest removal rate (reaching a maximum of 57.87%), followed by hydrolysis (reaching a maximum of 34.13%), and photolysis (less than 5%) after five days. The photosynthetic pigment contents in cells of microalga decreased the most (by 35.66% for chlorophyll a), and the production of ROS was stimulated (by 33.75%) after five-day exposure to ERY at an initial concentration of 100 μg/L. Meanwhile, the activity of ribulose-1,5-biphosphate carboxylase (RuBPCase) decreased by 55.65%, and the activity of acetyl-CoA carboxylase (ACCase) increased by 55.65%. The ROS level, photosynthetic pigment content, and RuBPCase activity were extremely significantly correlated with each other (P less then 0.01), indicating that exposure to ERY changed those biochemical responses related to the rate of photosynthesis of microalga, inhibiting the growth thereof. MG149 solubility dmso On the other hand, exposure to ERY increased lipid production by microalga through the induced ACCase activity.Ambient air pollution has been identified as one of the leading causes of global burden of disease. The relationship between ambient air pollution exposure and risk of chronic kidney disease (CKD) has stimulated increasing scientific interest in the past few years. However, evidence from human epidemiological studies is still limited and inconsistent. We performed an updated systematic review and meta-analysis to clarify the potential association comprehensively. Selected electronic databases were searched for related English language studies until March 1, 2020 with a final follow-up in December 31, 2020. Risk of bias assessment for individual studies were assessed using the OHAT (Office of Health Assessment and Translation) risk-of-bias rating tool. Confidence rating and level-of-evidence conclusions were developed for bodies of evidence for a given ambient air pollutant. Summary effect estimates were calculated using random-effects meta-analyses when three or more studies are identified for the same air pollutant-CKD combination. A total of 13 studies were finally identified in our study. The meta-analytic estimates (ORs) for risk of CKD were 1.15 (95% CI 1.07, 1.24) for each 10 μg/m3 increase in PM2.5, 1.25 (95% CI 1.11, 1.40) for each 10 μg/m3 increase in PM10, 1.10 (95% CI 1.03, 1.17) for each 10 ppb increase in NO2, 1.06 (95% CI 0.98, 1.15) for each 1 ppb increase in SO2 and 1.04 (95% CI 1.00, 1.08) for each 0.1 ppm increase in CO, respectively. The level of evidence was appraised as moderate for four of the five tested air pollutant-CKD combinations using an adaptation of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool. In conclusion, this study suggests that certain ambient air pollutant exposure was significantly associated with an increased risk of CKD. Given the limitations, the results of this study should be interpreted with caution, and further well-designed epidemiological studies are needed to draw a definite evidence of a causal relationship.