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Two NADPH: Protochlorophyllide Oxidoreductase (POR) Isoforms Play Distinct Roles in Environmental Adaptation in Rice
No full textAbstract
Background
NADPH: protochlorophyllide oxidoreductase (POR) is an essential enzyme that catalyzes the photoreduction of protochlorophyllide to chlorophyllide, which is ultimately converted to chlorophyll in developing leaves. Rice has two POR isoforms, OsPORA and OsPORB. OsPORA is expressed in the dark during early leaf development; OsPORB is expressed throughout leaf development regardless of light conditions. The faded green leaf ( fgl ) is a loss-of-function osporB mutant that displays necrotic lesions and variegation in the leaves due to destabilized grana thylakoids, and has increased numbers of plastoglobules in the chloroplasts. To investigate whether the function of OsPORA can complement that of OsPORB, we constitutively overexpressed OsPORA in fgl mutant.
Results
In the 35S:OsPORA/fgl (termed OPAO) transgenic plants, the necrotic lesions of the mutant disappeared and the levels of photosynthetic pigments and proteins, as well as plastid structure, were recovered in developing leaves under natural long days in the paddy field and under short days in an artificially controlled growth room. Under constant light conditions, however, total chlorophyll and carotenoid levels in the developing leaves of OPAO plants were lower than those of wild type. Moreover, the OPAO plants exhibited mild defects in mature leaves beginning at the early reproductive stage in the paddy field.
Conclusions
The physiological function of OsPORB in response to constant light or during reproductive growth cannot be completely replaced by constitutive activity of OsPORA, although the biochemical functions of OsPORA and OsPORB are redundant. Therefore, we suggest that the two OsPORs have differentiated over the course of evolution, playing distinct roles in the adaptation of rice to the environment
Application of a Bayesian dominance model improves power in quantitative trait genome-wide association analysis
No full textAbstract
Background
Multi-marker methods, which fit all markers simultaneously, were originally tailored for genomic selection purposes, but have proven to be useful also in association analyses, especially the so-called BayesC Bayesian methods. In a recent study, BayesD extended BayesC towards accounting for dominance effects and improved prediction accuracy and persistence in genomic selection. The current study investigated the power and precision of BayesC and BayesD in genome-wide association studies by means of stochastic simulations and applied these methods to a dairy cattle dataset.
Methods
The simulation protocol was designed to mimic the genetic architecture of quantitative traits as realistically as possible. Special emphasis was put on the joint distribution of the additive and dominance effects of causative mutations. Additive marker effects were estimated by BayesC and additive and dominance effects by BayesD. The dependencies between additive and dominance effects were modelled in BayesD by choosing appropriate priors. A sliding-window approach was used. For each window, the R. Fernando window posterior probability of association was calculated and this was used for inference purpose. The power to map segregating causal effects and the mapping precision were assessed for various marker densities up to full sequence information and various window sizes.
Results
Power to map a QTL increased with higher marker densities and larger window sizes. This held true for both methods. Method BayesD had improved power compared to BayesC. The increase in power was between \u22122 and 8% for causative genes that explained more than 2.5% of the genetic variance. In addition, inspection of the estimates of genomic window dominance variance allowed for inference about the magnitude of dominance at significant associations, which remains hidden in BayesC analysis. Mapping precision was not substantially improved by BayesD.
Conclusions
BayesD improved power, but precision only slightly. Application of BayesD needs large datasets with genotypes and own performance records as phenotypes. Given the current efforts to establish cow reference populations in dairy cattle genomic selection schemes, such datasets are expected to be soon available, which will enable the application of BayesD for association mapping and genomic prediction purposes
Comprehensive CircRNA expression profile and selection of key CircRNAs during priming phase of rat liver regeneration
No full textAbstract
Background
Rat liver regeneration (LR) proceeds along a process of highly organized and ordered tissue growth in response to the loss or injury of liver tissue, during which many physiological processes may play important roles. The molecular mechanism of hepatocyte proliferation, energy metabolism and substance metabolism during rat LR had been elucidated. Further, the correlation of circular RNA (circRNA) abundance with proliferation has recently been clarified. However, the regulatory capacity of circRNA in rat LR remains a fascinating topic.
Results
To investigate the regulatory mechanism of circRNA during priming phase of rat LR, high-throughput RNA sequencing technology was performed to unbiasedly profile the expression of circRNA during priming phase of rat LR. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis was conducted to predict the functions of differentially expressed circRNAs and their host linear transcripts. Co-expression networks of circRNA-miRNA were constructed based on the correlation analysis between the differentially expressed LR-related circRNAs and the condition of their miRNA binding sites. To excavate the key circRNAs in the early phase of rat LR, we comprehensively evaluated and integrated the relationship of expression level between the circRNAs and the linear transcripts as well as the distribution of miRNA binding sites in circRNA sequences.
Conclusions
This paper is the first to employ the comprehensive circRNA expression profile and to investigate circRNA-miRNA interactions during priming phase of rat LR. Two thousand four hundred twelve circRNAs were detected, and 159 circRNAs deriving from 116 host linear transcripts differentially expressed ( p \u2009<\u20090.05). Six significantly changed circRNAs during priming phase of rat LR were screened as key circle molecules, and then were validated by qRT-PCR. This study will lay the foundation for revealing the functional roles of circRNAs during rat LR and help solve the remaining clinical problems
Nucleotide diversity inflation as a genome-wide response to experimental lifespan extension in Drosophila melanogaster
No full textAbstract
Background
Evolutionary theory predicts that antagonistically selected alleles, such as those with divergent pleiotropic effects in early and late life, may often reach intermediate population frequencies due to balancing selection, an elusive process when sought out empirically. Alternatively, genetic diversity may increase as a result of positive frequency-dependent selection and genetic purging in bottlenecked populations.
Results
While experimental evolution systems with directional phenotypic selection typically result in at least local heterozygosity loss, we report that selection for increased lifespan in Drosophila melanogaster leads to an extensive genome-wide increase of nucleotide diversity in the selected lines compared to replicate control lines, pronounced in regions with no or low recombination, such as chromosome 4 and centromere neighborhoods. These changes, particularly in coding sequences, are most consistent with the operation of balancing selection and the antagonistic pleiotropy theory of aging and life history traits that tend to be intercorrelated. Genes involved in antioxidant defenses, along with multiple lncRNAs, were among those most affected by balancing selection. Despite the overwhelming genetic diversification and the paucity of selective sweep regions, two genes with functions important for central nervous system and memory, Ptp10D and Ank2 , evolved under positive selection in the longevity lines.
Conclusions
Overall, the \u2018evolve-and-resequence\u2019 experimental approach proves successful in providing unique insights into the complex evolutionary dynamics of genomic regions responsible for longevity
Heterogeneous pattern of DNA methylation in developmentally important genes correlates with its chromatin conformation
No full textAbstract
Background
DNA methylation is a major epigenetic modification, playing a crucial role in the development and differentiation of higher organisms. DNA methylation is also known to regulate transcription by gene repression. Various developmental genes such as c-mos, HoxB5, Sox11, and Sry show tissue-specific gene expression that was shown to be regulated by promoter DNA methylation. The aim of the present study is to investigate the establishment of chromatin marks (active or repressive) in relation to heterogeneous methylation in the promoter regions of these developmentally important genes.
Results
Chromatin-immunoprecipitation (ChIP) assays were performed to immuno-precipitate chromatin by antibodies against both active (H3K4me3) and repressive (H3K9me3) chromatin regions. The analysis of ChIP results showed that both the percentage input and fold enrichment of activated chromatin was higher in tissues expressing the respective genes as compared to the tissues not expressing the same set of genes. This was true for all the genes selected for the study (c-mos, HoxB5, Sox11, and Sry). These findings illustrate that inconsistent DNA methylation patterns (sporadic, mosaic and heterogeneous) may also influence gene regulation, thereby resulting in the modulation of chromatin conformation.
Conclusions
These findings illustrate that various patterns of DNA methylation (asynchronous, mosaic and heterogeneous) correlates with chromatin modification, resulting in the gene regulation
Brain metabolic pattern analysis using a magnetic resonance spectra classification software in experimental stroke
No full textAbstract
Background
Magnetic resonance spectroscopy (MRS) provides non-invasive information about the metabolic pattern of the brain parenchyma in vivo. The SpectraClassifier software performs MRS pattern-recognition by determining the spectral features (metabolites) which can be used objectively to classify spectra. Our aim was to develop an Infarct Evolution Classifier and a Brain Regions Classifier in a rat model of focal ischemic stroke using SpectraClassifier.
Results
A total of 164 single-voxel proton spectra obtained with a 7 Tesla magnet at an echo time of 12\ua0ms from non-infarcted parenchyma, subventricular zones and infarcted parenchyma were analyzed with SpectraClassifier ( http://gabrmn.uab.es/?q=sc ). The spectra corresponded to Sprague-Dawley rats (healthy rats, n\ua0=\ua07) and stroke rats at day 1 post-stroke (acute phase, n\ua0=\ua06 rats) and at days 7\ua0\ub1\ua01 post-stroke (subacute phase, n\ua0=\ua014). In the Infarct Evolution Classifier, spectral features contributed by lactate\ua0+\ua0mobile lipids (1.33\ua0ppm), total creatine (3.05\ua0ppm) and mobile lipids (0.85\ua0ppm) distinguished among non-infarcted parenchyma (100% sensitivity and 100% specificity), acute phase of infarct (100% sensitivity and 95% specificity) and subacute phase of infarct (78% sensitivity and 100% specificity). In the Brain Regions Classifier, spectral features contributed by myoinositol (3.62\ua0ppm) and total creatine (3.04/3.05\ua0ppm) distinguished among infarcted parenchyma (100% sensitivity and 98% specificity), non-infarcted parenchyma (84% sensitivity and 84% specificity) and subventricular zones (76% sensitivity and 93% specificity).
Conclusion
SpectraClassifier identified candidate biomarkers for infarct evolution (mobile lipids accumulation) and different brain regions (myoinositol content)
Patients\u2019 and physicians\u2019 perceptions and attitudes about oral anticoagulation and atrial fibrillation: a qualitative systematic review
No full textAbstract
Background
Oral anticoagulant therapy reduces the risk of stroke in patients with atrial fibrillation, but many patients are still not prescribed this therapy. The causes of underuse of vitamin K antagonists oral anticoagulants are not clear but could be related, in part, to patients\u2019 and physicians\u2019 perceptions and attitudes towards the benefits and downsides of this treatment. The purpose of this systematic review was to evaluate and synthesize patients\u2019 and physicians\u2019 perceptions and attitudes towards the benefits and downsides of vitamin K antagonist, in order to explore potential factors related with its underuse.
Methods
We included studies that used qualitative or mixed methods and focused on patients\u2019 and/or physicians\u2019 perceptions and attitudes towards oral anticoagulation. We systematically searched PubMed, EMBASE, ISI WoK, and PsycINFO from their inception until May 2013. Two reviewers independently assessed the quality of the included studies and synthesized results using a thematic analysis approach.
Results
We included a total of nine studies. In four studies, the quality assessed was excellent and in five was moderate. We identified three themes that were of interest to both physicians and patients: information to reinforce anticoagulation use, balance of benefits and downsides, roles in decision-making and therapy management. Three additional themes were of interest to patients: knowledge and understanding, impact on daily life, and satisfaction with therapy. The main difficulties with the use of anticoagulant treatment according to physicians were the perceived uncertainty, need of individualised decision-making, and the feeling of delegated responsibility as their main concerns. The main factors for patients were the lack of information and understanding.
Conclusion
Physicians\u2019 and patients\u2019 perceptions and attitudes might be potential factors in the underuse of treatment with vitamin K antagonists. Improving the quality and usability of clinical guidelines, developing tools to help with the decision-making, enhancing coordination between primary care and hospital care, and improving information provided to patients could help improve the underuse of anticoagulation
A double-blind, randomized, placebo-controlled trial of combined calcitriol and ergocalciferol versus ergocalciferol alone in chronic kidney disease with proteinuria
No full textAbstract
Background
KDOQI guideline suggests that nutritional vitamin D should be supplemented in chronic kidney disease (CKD) patients who have vitamin D insufficiency/deficiency. However, there are scarce data regarding the additional benefit of active vitamin D supplement in CKD patients who were receiving nutritional vitamin D supplement. This study was conducted to explore the effect of adding active vitamin D to nutritional vitamin D supplement on proteinuria and kidney function in CKD with vitamin D insufficiency/deficiency.
Methods
This double-blind, randomized placebo-controlled trial was performed to answer the above question. Sixty-eight patients with CKD stage 3\u20134, urine protein to creatinine ratio (UPCR)\u2009>\u20091\ua0g/g, and serum 25OH-D level\u2009<\u200930\ua0ng/mL were enrolled. Patients were randomly assigned to receive 12-week treatment with oral ergocalciferol plus placebo ( n \u2009=\u200936) or oral ergocalciferol plus calcitriol ( n \u2009=\u200932).
Results
The mean baseline values of UPCR of both groups were comparable (3.6\u2009\ub1\u20093.8\ua0g/g in combined group and 3.5\u2009\ub1\u20093.0\ua0g/g in ergocalciferol group). Following 12-week treatment, there were significant reductions in UPCR from baseline in both groups (2.3\u2009\ub1\u20092.1\ua0g/g in combined group and 2.4\u2009\ub1\u20092.0\ua0g/g in ergocalciferol group). The percentage reductions in UPCR of both groups were not significantly different. The mean eGFR and blood pressure did not differ between baseline and 12-week follow-up and between both groups. No severe hypercalcemia or serious side effects were noted in both groups.
Conclusions
The proteinuria lowering effect of ergocalciferol in CKD patients with vitamin D deficiency was demonstrated. Additional calcitriol supplement did not have more effects on proteinuria.
Trial registration
(Thai Clinical Trials Registry (TCTR) 20140929002 ). Date of registration: September 27, 2014
Acute and chronic kidney disease in elderly patients with hip fracture: prevalence, risk factors and outcome with development and validation of a risk prediction model for acute kidney injury
No full textAbstract
Background
Hip fracture is a common injury in older people with a high rate of postoperative morbidity and mortality. This patient group is also at high risk of acute kidney injury (AKI) and chronic kidney disease (CKD), but little is known of the impact of kidney disease on outcome following hip fracture.
Methods
An observational cohort of consecutive patients with hip fracture in a large UK secondary care hospital. Predictive modelling of outcomes using development and validation datasets. Inclusion: all patients admitted with hip fracture with sufficient serum creatinine measurements to define acute kidney injury. Main outcome measures \u2013 development of acute kidney injury during admission; mortality (in hospital, 30-365 day and to follow-up); length of hospital stay.
Results
Data were available for 2848 / 2959 consecutive admissions from 2007-2011; 776 (27.2%) male. Acute kidney injury occurs in 24%; development of acute kidney injury is independently associated with male sex (OR 1.48 (1.21 to 1.80), premorbid chronic kidney disease stage 3B or worse (OR 1.52 (1.19 to 1.93)), age (OR 3.4 (2.29 to 5.2) for >85\ua0years) and greater than one major co-morbidities (OR 1.61 (1.34 to 1.93)). Acute kidney injury of any stage is associated with an increased hazard of death, and increased length of stay (Acute kidney injury: 19.1 (IQR 13 to 31) days; no acute kidney injury 15 (11 to 23) days). A simplified predictive model containing Age, CKD stage (3B-5), two or more comorbidities, and male sex had an area under the ROC curve of 0.63 (0.60 to 0.67).
Conclusions
Acute kidney injury following hip fracture is common and associated with worse outcome and greater hospital length of stay. With the number of people experiencing hip fracture predicted to rise, recognition of risk factors and optimal perioperative management of acute kidney injury will become even more important
Prevalence and risk factors for cardiovascular disease among chronic kidney disease patients: results from the Chinese cohort study of chronic kidney disease (C-STRIDE)
No full textAbstract
Background
Although a high incidence of cardiovascular disease (CVD) is observed among chronic kidney disease (CKD) patients in developed countries, limited information is available about CVD prevalence and risk factors in the Chinese CKD population. The Chinese Cohort of Chronic Kidney Disease (C-STRIDE) was established to investigate the prevalence and risk factors of CVD among Chinese CKD patients.
Methods
Participants with stage 1\u20134 CKD (18\u201374 years of age) were recruited at 39 clinical centers located in 28 cities from 22 provinces of China. At entry, the socio-demographic status, medical history, anthropometric measurements and lifestyle behaviors were documented, and blood and urine samples were collected. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI creatinine equation. CVD diagnosis was based on patient self-report and review of medical records by trained staff. A multivariable logistic regression model was used to estimate the association between risk factors and CVD.
Results
Three thousand four hundred fifty-nine Chinese patients with pre-stage 5 CKD were enrolled, and 3168 finished all required examinations and were included in the study. In total, 40.8% of the cohort was female, with a mean age of 48.21\u2009\ub1\u200913.70\ua0years. The prevalence of CVD was 9.8%, and in 69.1% of the CVD cases cerebrovascular disease was observed. Multivariable analysis showed that increasing age, lower eGFR, presence of hypertension, abdominal aorta calcification and diabetes were associated with comorbid CVD among CKD patients. The odds ratios and 95% confidence intervals for these risk factors were 3.78 (2.55\u20135.59) for age 45\u201364 years and 6.07 (3.89\u20139.47) for age \u226565\ua0years compared with age <45\ua0years; 2.07 (1.28\u20133.34) for CKD stage 3a, 1.66 (1.00\u20132.62) for stage 3b, and 2.74 (1.72\u20134.36) for stage 4 compared with stages 1 and 2; 2.57 (1.50\u20134.41) for hypertension, 1.82 (1.23\u20132.70) for abdominal aorta calcification, and 1.70 (1.30\u20132.23) for diabetes, respectively.
Conclusions
We reported the CVD prevalence among a CKD patient cohort and found age, hypertension, diabetes, abdominal aorta calcification and lower eGFR were independently associated with higher ..