Ochratoxin A (OTA) is one of the most common and deleterious mycotoxins found in food and feedstuffs worldwide; however, Apiotrichum mycotoxinivorans can detoxify OTA. Our results show that A. ...mycotoxinivorans GUM1709 efficiently degraded OTA, but it caused the accumulation of intracellular reactive oxygen species. The main aim of this study was to identify potential OTA-detoxifying enzymes and to explore the effects of OTA on A. mycotoxinivorans GMU1709. RNA-seq data revealed that 1643 and 1980 genes were significantly upregulated and downregulated, respectively, after OTA exposure. Functional enrichment analyses indicated that OTA exposure enhanced defense capability, protein transport, endocytosis, and energy metabolism; caused ribosomal stress; suppressed DNA replication and transcription; inhibited cell growth and division; and promoted cell death. The integration of secretome, gene expression, and molecular docking analyses revealed that two carboxypeptidase homologues (members of the metallocarboxypeptidase family) were most likely responsible for the detoxification of both extracellular and intracellular OTA. Superoxide dismutase and catalase were the main genes activated in response to oxidative stress. In addition, analysis of key genes associated with cell division and apoptosis showed that OTA exposure inhibited mitosis and promoted cell death. This study revealed the possible OTA response and detoxification mechanisms in A. mycotoxinivorans.
Display omitted
•A. mycotoxinivorans GMU1709 efficiently degraded ochratoxin A (OTA).•OTA exposure induced metabolic pathways and genes involved in stress response.•CPA and CPY potentially contributed to OTA degradation in GMU1709.•Exposure to OTA may activate the antioxidant system of GMU1709.•OTA exposure inhibited the growth of GMU1709 and promoted its apoptosis.
Zearalenone (ZEN) is a potent oestrogenic mycotoxin that is mainly produced by Fusarium species and is a serious environmental pollutant in animal feeds. Apiotrichum mycotoxinivorans has been widely ...used as a feed additive to detoxify ZEN. However, the effects of ZEN on A. mycotoxinivorans and its detoxification mechanisms remain unclear. In this study, transcriptomic and bioinformatic analyses were used to investigate the molecular responses of A. mycotoxinivorans to ZEN exposure and the genetic basis of ZEN detoxification. We detected 1424 significantly differentially expressed genes (DEGs), of which 446 were upregulated and 978 were downregulated. Functional and enrichment analyses showed that ZEN-induced genes were significantly associated with xenobiotic metabolism, oxidative stress response, and active transport systems. However, ZEN-inhibited genes were mainly related to cell division, cell cycle, and fungal development. Subsequently, bioinformatic analysis identified candidate ZEN-detoxification enzymes. The Baeyer–Villiger monooxygenases and carboxylesterases, which are responsible for the formation and subsequent hydrolysis of a new ZEN lactone, respectively, were significantly upregulated. In addition, the expression levels of genes related to conjugation and transport involved in the xenobiotic detoxification pathway were significantly upregulated. Moreover, the expression levels of genes encoding enzymatic antioxidants and those related to growth and apoptosis were significantly upregulated and downregulated, respectively, which made it possible for A. mycotoxinivorans to survive in a highly toxic environment and efficiently detoxify ZEN. This is the first systematic report of ZEN tolerance and detoxification in A. mycotoxinivorans. We identified the metabolic enzymes that were potentially involved in detoxifying ZEN in the GMU1709 strain and found that ZEN-induced transcriptional regulation of genes is key to withstanding highly toxic environments. Hence, our results provide valuable information for developing enzymatic detoxification systems or engineering this detoxification pathway in other species.
•mycotoxinivorans GMU1709 strain can efficiently remove zearalenone (ZEN).•mycotoxinivorans possess complete xenobiotic detoxification pathways.•Exposure to ZEN would activate the antioxidant system of A. mycotoxinivorans.•Exposure to ZEN inhibit both the growth and apoptosis of A. mycotoxinivorans.
Phosphorus is an important macronutrient. To understand the molecular and cellular responses to phosphorus stress better, transcriptome profiling in combination with biochemical investigations was ...conducted in the model diatom Phaeodactylum tricornutum. Out of 10 402 predicted genes, 2491 and 405 genes were significantly upregulated or downregulated respectively. Unsurprisingly, genes associated with phosphate uptake were upregulated, such as the phosphate transporters and alkaline phosphatases. Genes encoding stress‐shock proteins were accordingly upregulated, including genes associated with stress‐responsive proteins, signal transduction and secondary metabolism. Additionally, genes related to protein translation, carbon fixation, glycolysis and the citric acid cycle were also upregulated. Genes associated with gene transcription were downregulated, thereby resulting in the upregulation of translation to compensate for the limited supply of messenger RNA. The downregulation of genes related to β‐oxidation could contribute to the accumulation of fatty acids. Accordingly, triacylglycerols, which are important for energy storage, were determined to increase by 1.65‐fold. Intracellular membranes, other than chloroplast membranes, tended to be dispersed; this finding was in accordance with the increased transcription of a total of 11 genes encoding putative phospholipases. Taken together, this work revealed the coordination of multiple metabolic pathways and certain key genes in the adaptation of P. tricornutum to phosphorus stress.
Cognitive impairment is an independent predictor of technique failure and mortality in patients on peritoneal dialysis (PD) therapy. We investigated changes in cognitive function and factors ...associated with it in this population.
Multicenter prospective cohort study.
458 PD patients were enrolled and followed up for 2 years.
Global and specific domains of cognitive function were measured at baseline and after 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of 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 skill, and language ability.
The primary outcome was change in cognitive function. Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalization, and transition to hemodialysis therapy.
Multivariable linear regression models.
The prevalence of cognitive impairment increased from 19.8% to 23.9%. 3MS scores significantly decreased (84.8 to 83.1), although executive function, immediate memory, and visuospatial skill improved over time. Delayed memory capacity and language ability were unchanged. Lower serum albumin level was associated with deteriorated delayed memory, visuospatial skill, and language ability, as well as with the decline in general cognitive function (β values of 0.64, 0.90, 0.80, and 0.44, respectively). Advanced age, lower education, and depression were also correlated with deterioration in general and specific cognitive function. After multivariable adjustment, both global and specific cognitive impairment at baseline were associated with a greater rate of hospitalization, and memory dysfunction was associated with a lower dialysis modality survival rate.
A relatively short observation period, small number of deaths, and potential selection bias due to patients unavailable for the second assessment.
In a PD population, global cognitive function declined over 2 years, though some specific cognitive domains improved. Besides well-recognized factors, hypoalbuminemia and depression were also risk factors for cognitive impairment.
It is estimated that 360,000 patients have suffered from heart failure (HF) in Taiwan, mostly those over the age of 65 years, who need long-term medication and daily healthcare to reduce the risk of ...mortality. The left ventricular ejection fraction (LVEF) is an important index to diagnose the HF. The goal of this study is to estimate the LVEF using the cardiovascular hemodynamic parameters, morphological characteristics of pulse, and bodily information with two machine learning algorithms. Twenty patients with HF who have been treated for at least six to nine months participated in this study. The self-constructing neural fuzzy inference network (SoNFIN) and XGBoost regression models were used to estimate their LVEF. A total of 193 training samples and 118 test samples were obtained. The recursive feature elimination algorithm is used to choose the optimal parameter set. The results show that the estimating root-mean-square errors (ERMS) of SoNFIN and XGBoost are 6.9 ± 2.3% and 6.4 ± 2.4%, by comparing with echocardiography as the ground truth, respectively. The benefit of this study is that the LVEF could be measured by the non-medical image method conveniently. Thus, the proposed method may arrive at an application level for clinical practice in the future.
Diatoms are important primary producers in the marine ecosystem. Currently it is difficult to genetically transform diatoms due to the technical limitations of existing methods. The ...promoter/terminator of the nitrate reductase gene of the model diatom Phaeodactylum tricornutum was cloned and used to drive chloramphenicol acetyltransferase (CAT) reporter gene expression. The construct was transferred by electroporation into P. tricornutum grown in medium lacking silicon. CAT expression was induced in transformed diatoms in the presence of nitrate, enabling growth in selective medium, and was repressed when ammonium was the only nitrogen source. Expression of CAT transcript and protein were demonstrated by RT-PCR and Western blot analysis, respectively. Our study is the first to report a successful genetic transformation of diatom by electroporation in an economical and efficient manner and provides a tightly regulated inducible gene expression system for diatom.
Over the past decade,
has been recognized globally as a source of opportunistic infections. It is a yeast-like fungus, and its association as an uncommon pulmonary pathogen with cystic fibrosis ...patients has been previously reported. Immunocompromised patients are at the highest risk of
infections. Therefore, to investigate the genetic basis for the pathogenicity of
, we performed whole-genome sequencing and comparative genomic analysis of
GMU1709 that was isolated from sputum specimens of a pneumonia patient receiving cardiac repair surgery. The assembly of Oxford Nanopore reads from the GMU1709 strain and its subsequent correction using Illumina paired-end reads yielded a high-quality complete genome with a genome size of 30.5 Mb in length, which comprised six chromosomes and one mitochondrion. Subsequently, 8,066 protein-coding genes were predicted based on multiple pieces of evidence, including transcriptomes. Phylogenomic analysis indicated that
exhibited the closest evolutionary affinity to
, and both the
strains and the formerly
ACCC 20271 strain occupied the same phylogenetic position. Further comparative analysis supported that the ACCC 20271 strain belonged to
. Comparisons of three
strains indicated that the differences between clinical and non-clinical strains in pathogenicity and drug resistance may be little or none. Based on the comparisons with strains of other species in the
family, we identified potential key genetic factors associated with
infection or pathogenicity. In addition, we also deduced that
had great potential to inactivate some antibiotics (
, tetracycline), which may affect the efficacy of these drugs in co-infection. In general, our analyses provide a better understanding of the classification and phylogeny of the
family, uncover the underlying genetic basis of
infections and associated drug resistance, and provide clues into potential targets for further research and the therapeutic intervention of infections.
Diabetes and retinopathy have been considered as risk factors of cognitive impairment (CI) in previous studies. We investigated both of these two factors and their relationship with global and ...specific cognitive functions in end stage renal disease patients under peritoneal dialysis (PD).
In this multicenter cross-sectional study, 424 clinically stable patients were enrolled from 5 PD units, who performed PD for at least three months and completed fundoscopy examination if they had diabetes. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms 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.
PD Patients with DM and Retinopathy had significantly higher prevalence of CI, executive dysfunction, impaired immediate memory and visuospatial skill, compared with patients in non-DM group. By multivariate logistic regression analyses, DM and retinopathy rather than DM only were significantly associated with increased risk for CI, executive dysfunction, impaired immediate memory and visuospatial skill, odds ratios(ORs) and 95% confidence intervals were 2.091.11,3.92, 2.891.55,5.37, 2.16 1.15,4.06 and 2.371.32,4.22, respectively (all P < 0.05).
Diabetic PD patients with retinopathy were at two times risk for overall cognitive impairment, executive dysfunction, impaired immediate memory and visuospatial skill as compared to non-diabetic PD patients.
Bacteria can usually acquire certain advantageous genes that enable the bacteria to adapt to rapidly changing niches, thereby leading to a wide range of intraspecific genome content and genetic ...redundancy. The minimal genome of Escherichia coli, which is the most important bacterial species, and the association between E.coli and its human host are worthy of further exploration.
We used gene prediction and phylogenetic analysis to reveal a rich phylogenetic diversity among 491 E.coli strains and to reveal substantial differences between these strains with respect to gene number and genome length. We used pan-genomic analysis to accurately identify 867 core genes, in which only 243 genes are shared by essential genes. This analysis revealed that core genes mainly provide essential functions to the basic lifestyle of E.coli, and accessory genes are likely to confer selective advantages such as niche adaptation or the ability to colonize specific hosts. By association analysis, we found that E.coli strains in non-human hosts may more easily utilize foreign genetic materials to adapt to their surroundings, but the population in human hosts has higher demands for the control of population density, indicating that highly accurate quorum-sensing behavior is very important for harmony between E.coli and its human host. By considering core genes and previous deletions together, we proposed a potential direction for further reduction of the E.coli genome.
The data, analysis process and detailed information on software tools used in this study are all available in the supplementary material.
Supplementary data are available at Bioinformatics online.
Abstract
Background
Vitamin D deficiency has been shown to be closely associated with peritoneal dialysis (PD)-related peritonitis. The aim of this study is to examine the feasibility of conducting a ...large, powered randomized controlled trial to determine the effects of vitamin D supplementation on the risk of PD-related peritonitis in patients who have already experienced an episode of peritonitis.
Methods
This prospective, open-label randomized controlled pilot trial with blinded end-points aims to determine the feasibility of oral vitamin D supplementation and to explore its effects on the risk of subsequent PD-related peritonitis among PD patients who have recovered from a recent episode of peritonitis. Eligible patients will be randomized 1:1 to either oral vitamin D supplementation (2000 IU per day; intervention group) or no vitamin D supplementation (control group) in addition to usual care according to International Society for Peritoneal Dialysis guidelines. The sample size will be 30 patients for both groups. All participants will be followed for 12 months. The primary outcome is the assessment of feasibility (recruitment success, retention, adherence, safety) and fidelity (change in serum 25-hydroxyvitamin D level during follow-up) for a large, powered randomized controlled trial to determine the effects of vitamin D on the risk of PD-related peritonitis in the future. Secondary outcomes include time to peritonitis occurrence, recovery of peritonitis, peritonitis-related transition to hemodialysis, and peritonitis-related death (defined as death within 30 days of peritonitis onset).
Discussion
This is the first randomized controlled trail investigating the effects of vitamin D supplementation on the risk of subsequent PD-related peritonitis among patients on PD. The findings for this pilot study will determine the feasibility of conducting a full-scale randomized controlled trail, which may provide a new strategy for preventing PD-related peritonitis among PD patients.
Trial registration
Clinicaltrails.gov,
NCT03264625
. Registered on 29 August 2017.
PDF
