Abstract
Motivation
The budding yeast Saccharomyces cerevisiae is a model species powerful for studying the recombination of eukaryotes. Although many recombination studies have been performed for ...this species by experimental methods, the population genomic study based on bioinformatics analyses is urgently needed to greatly increase the range and accuracy of recombination detection. Here, we carry out the population genomic analysis of recombination in S.cerevisiae to reveal the potential rules between recombination and evolution in eukaryotes.
Results
By population genomic analysis, we discover significantly more and longer recombination events in clinical strains, which indicates that adverse environmental conditions create an obviously wider range of genetic combination in response to the selective pressure. Based on the analysis of recombinational double strand breaks (DSBs)-intersected genes (RDIGs), we find that RDIGs significantly converge on specific disease- and adaptability-related pathways, indicating that recombination plays a biologically key role in the repair of DSBs related to diseases and environmental adaptability, especially the human neurological disorders. By evolutionary analysis of RDIGs, we find that the RDIGs highly prevailing in populations of yeast tend to be more evolutionarily conserved, indicating the accurate repair of DSBs in these RDIGs is critical to ensure the eukaryotic survival or fitness.
Supplementary information
Supplementary data are available at Bioinformatics online.
Background
Uremic toxins have been suspected as potential contributors for cognitive impairment in peritoneal dialysis (PD) patients. However, associations between the clearance of serum small and ...middle molecules and the change of cognitive function were not fully explored and then we explored this issue in the present study.
Method
A total of clinically-stable 222 patients on PD were enrolled and then followed up for 2 years in this single-center prospective cohort study. Small and middle molecules clearances were examined by urea clearance (Kt/V), creatinine clearance (Ccr) and beta-2 microglobulin (B2M) clearance via dialysate and urine at baseline and after 2 years. Global and specific cognitive impairment were measured at baseline and after 2 years. Modified Mini-Mental State Examination (3MS) was assessed for global cognitive function, trail-making tests A and B for executive function and subtests of the battery for the assessment of neuropsychological status for immediate and delayed memory, visuospatial skills and language ability.
Results
The median of total Kt/V, Ccr and B2M clearance were 1.89, 53.2 l/w/1.73 m
2
and 17.5 l/w/1.73 m
2
, respectively at baseline. The prevalence of global cognitive impairment was 12.3% for 222 patients and 15.4% for the remained 130 patients after 2 years. At baseline, total Kt/V was independently positively associated with delayed memory function. Total and dialysate beta-2 microglobulin clearance was positively associated with 3MS scores and negatively with completion time on trail A after multivariate adjustment. At 2 years, we observed a significant difference in the changing trend of 3MS scores between groups divided by total B2M clearance (
P
= 0.033), which still maintained to be meaningful after multivariate adjustment (
P
= 0.024). Patients with total B2M clearance > 19.0 l/w/1.73 m
2
got significant improvement on their 3MS scores (
P
= 0.005). Patients divided by total Kt/V or Ccr were not significantly different in the trends of general and any specific cognitive function during the follow up.
Conclusion
The higher middle molecules clearance independently correlated to better performance on general cognitive and executive function in PD patients, which also predict an improvement in general cognitive function during the follow up.
Background
Although the association between adipokines such as adiponectin, leptin, and body composition has been noted, whether they could predict the change of fat mass and lean body mass is ...unknown. We aimed to examine these associations in patients on peritoneal dialysis (PD) through a prospective cohort study.
Methods
Body composition (by dual-energy x-ray absorptiometry) including fat mass and lean body mass were examined at baseline and then at year 3. Serum leptin and adiponectin levels were measured. Demographic data, comorbidity, biochemical data, inflammation (high-sensitive C-reactive protein hs-CRP) and insulin resistance (homeostatic model assessment HOMA-IR) were also examined.
Results
At baseline, serum adiponectin levels were significantly inversely correlated with weight, lean body mass index (LBMI), fat mass index (FMI), lean body mass (LBM), and fat mass (FM) in 213 prevalent patients. At year 3, FMI, LBMI, FM, and the percentage of FM (FM%) increased while the percentage of LBM (LBM%) significantly decreased despite unchanged weight and LBM among the remaining 112 patients. After adjustment for demographic data, comorbidities, hs-CRP, HOMA-IR, and daily energy intake (DEI), serum adiponectin at baseline was not associated with increases in LBMI, FMI, and FM, but independently associated with an increase in FM% and a decrease in LBM%. The predictive effect of high-serum adiponectin level on mortality disappeared after adjusting for diabetes and cardiovascular disease. Serum leptin was not associated with any changes in body composition during the follow-up, nor with the mortality in this cohort.
Conclusions
A high adiponectin level could predict an increase in FM% and a decrease in LBM% during a 3-year follow-up in PD patients. Serum adiponectin could not independently predict mortality in PD patients.
Phosphorus (P) is an essential macronutrient for the survival of marine phytoplankton. In the present study, phytoplankton response to phosphorus limitation was studied by proteomic profiling in ...diatom Phaeodactylum tricornutum in both cellular and molecular levels. A total of 42 non-redundant proteins were identified, among which 8 proteins were found to be upregulated and 34 proteins were downregulated. The results also showed that the proteins associated with inorganic phosphate uptake were downregulated, whereas the proteins involved in organic phosphorus uptake such as alkaline phosphatase were upregulated. The proteins involved in metabolic responses such as protein degradation, lipid accumulation and photorespiration were upregulated whereas energy metabolism, photosynthesis, amino acid and nucleic acid metabolism tend to be downregulated. Overall our results showed the changes in protein levels of P. tricornutum during phosphorus stress. This study preludes for understanding the role of phosphorous in marine biogeochemical cycles and phytoplankton response to phosphorous scarcity in ocean. It also provides insight into the succession of phytoplankton community, providing scientific basis for elucidating the mechanism of algal blooms.
Microalgae have been an emerging biofuel resource; however, the germplasm improvement has been slow due to the lack of molecular tools. Pyruvate dehydrogenase kinase (PDK) deactivates the pyruvate ...dehydrogenase complex (PDC) which catalyzes the oxidative decarboxylation of pyruvate. Acetyl-CoA production via PDC is important in plant tissues that are active in fatty acid synthesis.
A 1261-bp cDNA of a putative PDK gene (PtPDK) was cloned from a diatom Phaeodactylum tricornutum, and PtPDK antisense knockdown transgenic diatoms were generated. Both PtPDK transcript abundance and enzyme activity were reduced significantly due to antisense knockdown of PtPDK. Neutral lipid content of transgenic diatom cells increased up to 82% as determined by Nile red staining, and fatty acid composition was not altered. Transgenic cells showed slightly lower growth rate but similar cell size with the wild type, hence retaining similar biomass productivity.
This work first obtained a successful engineered diatom regulating a key gene involved in lipid metabolism. Our findings also provide powerful indications in enhancing microalgal lipid production by metabolic engineering for biofuel industry.
We explored associations between markers of endothelial dysfunction and outcome events, and whether those associations were independent of residual renal function (RRF) in patients on peritoneal ...dialysis.
The study enrolled 261 incident patients and 68 healthy control subjects who were followed till death, censoring, or study end. Demographics, biochemistry, markers of inflammation (C-reactive protein) and endothelial dysfunction soluble intercellular adhesion molecule 1 (sICAM), soluble vascular adhesion molecule 1 (sVCAM), and von Willebrand factor (vWf) were examined at baseline. Outcome events included all-cause death and fatal and nonfatal cardiovascular (CV) events.
Mean levels of vWf, sICAM, and sVCAM were significantly higher in patients than in healthy control subjects. Levels of sICAM and sVCAM, but not vWf, were significantly correlated with RRF. Levels of sICAM and vWf both predicted all-cause mortality and fatal and nonfatal CV events after adjustment for recognizable CV risk factors. The association between sICAM and outcome events disappeared after further adjustment for RRF. However, RRF did not change the predictive role of vWf for outcome events. Compared with the lowest vWf quartile (6.6% - 73.9%), the highest vWf quartile (240.9% - 1161%) predicted the highest risk for fatal and nonfatal CV events (adjusted hazard ratio: 2.05; 95% confidence interval: 1.15 to 3.64; p = 0.014). We observed no associations between sVCAM and RRF, or sVCAM and any outcome event.
The prognostic value of vWf, but not sICAM, is independent of RRF in predicting mortality and CV events.
Benzimidazole scaffolds became an attractive subject due to their broad spectrum of pharmacological activities. In this work, a methodology was developed for the synthesis of N-substituted ...benzimidazole derivatives from benzimidazoles and α, β-unsaturated compounds (acrylonitriles, acrylate esters, phenyl vinyl sulfone) catalyzed by lipase TL IM from Thermomyces lanuginosus in continuous-flow microreactors. Investigations were conducted on reaction parameters such as solvent, substrate ratio, reaction temperature, reactant donor/acceptor structures, and reaction time. The transformation is promoted by inexpensive and readily available lipase in methanol at 45 °C for 35 min. A wide range of β-amino sulfone, β-amino nitrile, and β-amino carbonyl compounds were efficiently and selectively synthesized in high yields (76–97%). All in all, a microfluidic biocatalysis system was applied to the synthesis of N-substituted benzimidazole derivatives, and could serve as a promising fast synthesis strategy for further research to develop novel and highly potent active drugs.
Background
Cognitive impairment (CI) is a common phenomenon and predictive of high mortality in peritoneal dialysis (PD) patients. This study aimed to analyze the association of social support and ...family environment with cognitive function in PD patients.
Methods
This is a cross-sectional study of PD patients from Peking University First Hospital and the Second Affiliated Hospital of Harbin Medical University. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), executive function was measured by the A and B trail-making tests, and other cognitive functions were measured by the Repeatable Battery for the Assessment of Neuropsychological Status. Social support was measured with the Social Support Scale developed by Xiaoshuiyuan and family environment was measured with the Chinese Version of the Family Environment Scale (FES-CV).
Results
The prevalence of CI and executive dysfunction among the 173 patients in the study was, respectively, 16.8% and 26.3%. Logistic regression found that higher global social support (odds ratio OR = 1.09, 1.01 – 1.17, p = 0.027) and subjective social support predicted higher prevalence of CI (OR = 1.13, 1.02 – 1.25, p = 0.022), adjusting for covariates. Analyses of the FES-CV dimensions found that greater independence was significantly associated with better immediate memory and delayed memory. Moreover, higher scores on achievement orientation were significantly associated with poorer language skills.
Conclusions
Our findings indicate that social support is negatively associated with the cognitive function of PD patients and that some dimensions of the family environment are significantly associated with several domains of cognitive function.
♦
To develop and validate equations for estimating lean body mass (LBM) in peritoneal dialysis (PD) patients. ♦
Two equations for estimating LBM, one based on mid-arm muscle circumference (MAMC) and ...hand grip strength (HGS), i.e., LBM-M-H, and the other based on HGS, i.e., LBM-H, were developed and validated with LBM obtained by dual-energy X-ray absorptiometry (DEXA). The developed equations were compared to LBM estimated from creatinine kinetics (LBM-CK) and anthropometry (LBM-A) in terms of bias, precision, and accuracy. The prognostic values of LBM estimated from the equations in all-cause mortality risk were assessed. ♦
The developed equations incorporated gender, height, weight, and dialysis duration. Compared to LBM-DEXA, the bias of the developed equations was lower than that of LBM-CK and LBM-A. Additionally, LBM-M-H and LBM-H had better accuracy and precision. The prognostic values of LBM in all-cause mortality risk based on LBM-M-H, LBM-H, LBM-CK, and LBM-A were similar. ♦
Lean body mass estimated by the new equations based on MAMC and HGS was correlated with LBM obtained by DEXA and may serve as practical surrogate markers of LBM in PD patients.
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