Heart rhythm complexity analysis in patients with inferior ST-elevation myocardial infarction.

Heart rhythm complexity (HRC), a subtype of heart rate variability (HRV), is an important tool to investigate cardiovascular disease. In this study, we aimed to analyze serial changes in HRV and HRC metrics in patients with inferior ST-elevation myocardial infarction (STEMI) within 1 year postinfarct and explore the association between HRC and postinfarct left ventricular (LV) systolic impairment. We prospectively enrolled 33 inferior STEMI patients and 74 control subjects and analyzed traditional linear HRV and HRC metrics in both groups, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We also analyzed follow-up postinfarct echocardiography for 1 year. The STEMI group had significantly lower standard deviation of RR interval (SDNN), and DFAα2 within 7 days postinfarct (acute stage) comparing to control subjects. LF power was consistently higher in STEMI group during follow up. The MSE scale 5 was higher at acute stage comparing to control subjects and had a trend of decrease during 1-year postinfarct. The MSE area under scale 1-5 showed persistently lower than control subjects and progressively decreased during 1-year postinfarct. To predict long-term postinfarct LV systolic impairment, the slope between MSE scale 1 to 5 (slope 1-5) had the best predictive value. MSE slope 1-5 also increased the predictive ability of the linear HRV metrics in both the net reclassification index and integrated discrimination index models. In conclusion, HRC and LV contractility decreased 1 year postinfarct in inferior STEMI patients, and MSE slope 1-5 was a good predictor of postinfarct LV systolic impairment.

MtNF-YC6 and MtNF-YC11 are involved in regulating the transcriptional program of arbuscular mycorrhizal symbiosis.

Arbuscular mycorrhizal fungi are obligate symbionts that transfer mineral nutrients to host plants through arbuscules, a fungal structure specialized for exchange for photosynthetic products. MtNF-YC6 and MtNF-YC11, which encode the C subunits of nuclear factor Y (NF-Y) family in Medicago truncatula are induced specifically by arbuscular mycorrhizal symbiosis (AMS). A previous study showed that MtNF-YC6 and MtNF-YC11 are activated in cortical cells of mycorrhizal roots, but the gene functions were unknown. Herein, we identified both MtNF-YB17 and MtNF-YB12 as the interacting partners of MtNF-YC6 and MtNF-YC11 in yeast and plants. MtNF-YB17 was highly induced by AMS and activated in cortical cells only in mycorrhizal roots but MtNF-YB12 was not affected. The formation of B/C heterodimers led the protein complexes to transfer from the cytoplasm to the nucleus. Silencing MtNF-YC6 and C11 by RNA interference (RNAi) resulted in decreased colonization efficiency and arbuscule richness. Coincidently, genes associated with arbuscule development and degeneration in RNAi roots were also downregulated. In silico analysis showed CCAAT-binding motifs in the promoter regions of downregulated genes, further supporting the involvement of NF-Y complexes in transcriptional regulation of symbiosis. Taken together, this study identifies MtNF-YC6- or MtNF-YC11-containing protein complexes as novel transcriptional regulators of symbiotic program and provides a list of potential downstream target genes. These data will help to further dissect the AMS regulatory network.

KCNJ5 Somatic Mutations in Aldosterone-Producing Adenoma Are Associated with a Greater Recovery of Arterial Stiffness.

Primary aldosteronism is the most common form of secondary hypertension and induces various cardiovascular injuries. In aldosterone-producing adenoma (APA), the impact of KCNJ5 somatic mutations on arterial stiffness excluding the influence of confounding factors is uncertain. We enrolled 213 APA patients who were scheduled to undergo adrenalectomy. KCNJ5 gene sequencing of APA was performed. After propensity score matching (PSM) for age, sex, body mass index, blood pressure, number of hypertensive medications, and hypertension duration, there were 66 patients in each group with and without KCNJ5 mutations. The mutation carriers had a higher aldosterone level and lower log transformed brachial-ankle pulse wave velocity (baPWV) than the non-carriers before PSM, but no difference in log baPWV after PSM. One year after adrenalectomy, the mutation carriers had greater decreases in log plasma aldosterone concentration, log aldosterone-renin activity ratio, and log baPWV than the non-carriers after PSM. Only the mutation carriers had a significant decrease in log baPWV after surgery both before and after PSM. KCNJ5 mutations were not correlated with baseline baPWV after PSM but were significantly correlated with ∆baPWV after surgery both before and after PSM. Conclusively, APA patients with KCNJ5 mutations had a greater regression in arterial stiffness after adrenalectomy than those without mutations.

FluConvert and IniFlu: a suite of integrated software to identify novel signatures of emerging influenza viruses with increasing risk.

BACKGROUND: The pandemic threat of influenza has attracted great attention worldwide. To assist public health decision-makers, new suites of tools are needed to rapidly process and combine viral information retrieved from public-domain databases for a better risk assessment. RESULTS: Using our recently developed FluConvert and IniFlu software, we automatically processed and rearranged sequence data by standard viral nomenclature, determined the group-related consensus sequences, and identified group-specific polygenic signatures. The software possesses powerful ability to integrate viral, clinical, and epidemiological data. We demonstrated that both multiple basic amino acids at the cleavage site of the HA gene and also at least 11 more evidence-based viral amino acid substitutions present in global highly pathogenic avian influenza H5N2 viruses during the years 2009-2016 that are associated with viral virulence and human infection. CONCLUSIONS: FluConvert and IniFlu are useful to monitor and assess all subtypes of influenza viruses with pandemic potential. These programs are implemented through command-line and user-friendly graphical interfaces, and identify molecular signatures with virological, epidemiological and clinical significance. FluConvert and IniFlu are available at https://apps.flutures.com or https://github.com/chinrur/FluConvert_IniFlu.

Psychological distress of suicide attempters predicts one-year suicidal deaths during 2007-2016: A population-based study.

BACKGROUND/PURPOSE: Of the risk factors for suicide, prior attempt is regarded as one of the strongest for subsequent attempts or completed suicide. This large-scale cohort study aims to examine whether the distress level of individual mental symptoms and general psychopathology measured at the index attempt can predict subsequent suicide death within one year. METHODS: The participants were 104,441 suicide attempters first reported to the Taiwan National Suicide Surveillance System during 2007-2016, who completed the five-item Brief Symptom Rating Scale (BSRS-5) at the index attempt. Kaplan-Meier survival curve analysis with log-rank test and Cox regression model were used to examine whether the level of psychological distress could predict the cumulative incidence of re-attempted suicidal death in the following year. RESULTS: In total, 1254 (1.2%) participants subsequently killed themselves within one year. Survival curves analysis and Cox regression modelling indicated that levels of distress of individual items (i.e., suicide ideation, depression, inferiority, anxiety, hostility and insomnia) and total BSRS-5 scores were significantly correlated with the incidence of subsequent suicidal death within one year for both genders. CONCLUSION: The study revealed that self-rated psychological distress was a significant and sustained predictor of re-attempted suicide death within one year after the index attempt. These results imply that suicide is not only an issue of acute crisis, but also a prolonged problem of lasting psychological distress. The BSRS-5 assessment could provide a symptom profile on which to develop a pertinent person-centered approach to prevent subsequent suicide attempts.

Chromatin Organization in Early Land Plants Reveals an Ancestral Association between H3K27me3, Transposons, and Constitutive Heterochromatin.

Genome packaging by nucleosomes is a hallmark of eukaryotes. Histones and the pathways that deposit, remove, and read histone modifications are deeply conserved. Yet, we lack information regarding chromatin landscapes in extant representatives of ancestors of the main groups of eukaryotes, and our knowledge of the evolution of chromatin-related processes is limited. We used the bryophyte Marchantia polymorpha, which diverged from vascular plants circa 400 mya, to obtain a whole chromosome genome assembly and explore the chromatin landscape and three-dimensional genome organization in an early diverging land plant lineage. Based on genomic profiles of ten chromatin marks, we conclude that the relationship between active marks and gene expression is conserved across land plants. In contrast, we observed distinctive features of transposons and other repetitive sequences in Marchantia compared with flowering plants. Silenced transposons and repeats did not accumulate around centromeres. Although a large fraction of constitutive heterochromatin was marked by H3K9 methylation as in flowering plants, a significant proportion of transposons were marked by H3K27me3, which is otherwise dedicated to the transcriptional repression of protein-coding genes in flowering plants. Chromatin compartmentalization analyses of Hi-C data revealed that repressed B compartments were densely decorated with H3K27me3 but not H3K9 or DNA methylation as reported in flowering plants. We conclude that, in early plants, H3K27me3 played an essential role in heterochromatin function, suggesting an ancestral role of this mark in transposon silencing.

Heart Rhythm Complexity Predicts Long-Term Cardiovascular Outcomes in Peritoneal Dialysis Patients: A Prospective Cohort Study.

Background Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage renal disease. Heart rhythm complexity analysis has been shown to be useful in predicting outcomes in various diseases; however, data on patients with end-stage renal disease are limited. In this study, we analyzed the association between heart rhythm complexity and long-term cardiovascular outcomes in patients with end-stage renal disease receiving peritoneal dialysis. Methods and Results We prospectively enrolled 133 patients receiving peritoneal dialysis and analyzed linear heart rate variability and heart rhythm complexity variables including detrended fluctuation analysis (DFA) and multiscale entropy. The primary outcome was cardiovascular mortality, and the secondary outcome was the occurrence of major adverse cardiovascular events. After a median of 6.37 years of follow-up, 21 patients (22%) died from cardiovascular causes. These patients had a significantly lower low-frequency band of heart rate variability, low/high-frequency band ratio, total power band of heart rate variability, heart rate turbulence slope, deceleration capacity, short-term DFA (DFAα1); and multiscale entropy slopes 1 to 5, scale 5, area 1 to 5, and area 6 to 20 compared with the patients who did not die from cardiovascular causes. Time-dependent receiver operating characteristic curve analysis showed that DFAα1 had the greatest discriminatory power for cardiovascular mortality (area under the curve: 0.763) and major adverse cardiovascular events (area under the curve: 0.730). The best cutoff value for DFAα1 was 0.98 to predict both cardiovascular mortality and major adverse cardiovascular events. Multivariate Cox regression analysis showed that DFAα1 (hazard ratio: 0.076; 95% CI, 0.016-0.366; P=0.001) and area 1 to 5 (hazard ratio: 0.645; 95% CI, 0.447-0.930; P=0.019) were significantly associated with cardiovascular mortality. Conclusions Heart rhythm complexity appears to be a promising noninvasive tool to predict long-term cardiovascular outcomes in patients receiving peritoneal dialysis.

Construction of gene causal regulatory networks using microarray data with the coefficient of intrinsic dependence.

BACKGROUND: In the past two decades, biologists have been able to identify the gene signatures associated with various phenotypes through the monitoring of gene expressions with high-throughput biotechnologies. These gene signatures have in turn been successfully applied to drug development, disease prevention, crop improvement, etc. However, ignoring the interactions among genes has weakened the predictive power of gene signatures in practical applications. Gene regulatory networks, in which genes are represented by nodes and the associations between genes are represented by edges, are typically constructed to analyze and visualize such gene interactions. More specifically, the present study sought to measure gene-gene associations by using the coefficient of intrinsic dependence (CID) to capture more nonlinear as well as cause-effect gene relationships. RESULTS: A stepwise procedure using the CID along with the partial coefficient of intrinsic dependence (pCID) was demonstrated for the rebuilding of simulated networks and the well-known CBF-COR pathway under cold stress using Arabidopsis microarray data. The procedure was also applied to the construction of bHLH gene regulatory pathways under abiotic stresses using rice microarray data, in which OsbHLH104, a putative phytochrome-interacting factor (OsPIF14), and OsbHLH060, a positive regulator of iron homeostasis (OsPRI1) were inferred as the most affiliated genes. The inferred regulatory pathways were verified through literature reviews. CONCLUSIONS: The proposed method can efficiently decipher gene regulatory pathways and may assist in achieving higher predictive power in practical applications. The lack of any mention in the literature of some of the regulatory event may have been due to the high complexity of the regulatory systems in the plant transcription, a possibility which could potentially be confirmed in the near future given ongoing rapid developments in bio-technology.

The association between heart rhythm complexity and the severity of abdominal aorta calcification in peritoneal dialysis patients.

Abdominal aorta calcification (AAC) has been associated with clinical outcomes in peritoneal dialysis (PD) patients. Heart rhythm complexity analysis has been shown to be a promising tool to predict outcomes in patients with cardiovascular disease. In this study, we aimed to analyze the association between heart rhythm complexity and AAC in PD patients. We prospectively analyzed 133 PD patients. Heart rhythm complexity including detrended fluctuation analysis and multiscale entropy was performed. In linear analysis, the patients in the higher AAC group (AAC ≥15%) had a significantly lower standard deviation of normal RR intervals, very low frequency, low frequency, high frequency and low/high frequency ratio. In non-linear analysis, DFAα1, slope 1-5, scale 5 and area 6-20 were significantly lower in the patients with higher AAC. Receiver operating characteristic curve analysis showed that DFAα1 had the greatest discriminatory power to differentiate these two groups. Multivariate logistic regression analysis showed that DFAα1 and HbA1c were significantly associated with higher AAC ratio. Adding DFAα1 significantly improved the discriminatory power of the linear parameters in both net reclassification improvement and integrated discrimination improvement models. In conclusion, DFAα1 is highly associated with AAC and a potential cardiovascular marker in PD patients.

Gene-to-Gene Network Analysis of the Mediation of Plant Innate Immunity by the Eliciting Plant Response-Like 1 (Epl1) Elicitor of Trichoderma formosa.

A new clade, Trichoderma formosa, secretes eliciting plant response-like 1 (Epl1), a small peptide elicitor that stimulates plant immunity. Nicotiana benthamiana pretreated with Epl1 for 3 days developed immunity against Tomato mosaic virus (ToMV) infection. The transcriptome profiles of T. formosa and N. benthamiana were obtained by deep sequencing; the transcript of Epl1 is 736 nt in length and encodes a 12-kDa peptide. Identifying critical genes in Epl1-mediated immunity was challenging due to high similarity between the transcriptome expression profiles of Epl1-treated and ToMV-infected N. benthamiana samples. Therefore, an efficient bioinformatics data mining approach was used for high-throughput transcriptomic assays in this study. We integrated gene-to-gene network analysis into the ContigViews transcriptome database, and genes related to jasmonic acid and ethylene signaling, salicylic acid signaling, leucine-rich repeats, transcription factors, and histone variants were hubs in the gene-to-gene networks. In this study, the Epl1 of T. formosa triggers plant immunity against various pathogen infections. Moreover, we demonstrated that high-throughput data mining and gene-to-gene network analysis can be used to identify critical candidate genes for further studies on the mechanisms of plant immunity.

The relationship among cardiac structure, dietary salt and aldosterone in patients with primary aldosteronism.

Salt intake is highly associated with cardiac structure in patients with primary aldosteronism (PA). We investigated the association among dietary salt intake, aldosterone and left ventricular mass in patients with PA. We enrolled 158 patients with PA and 158 patients with essential hypertension. We measured 24-hour urinary sodium (UNa) and aldosterone (UAldo) level and echocardiography parameters. In patients with PA, the UAldo level was positively correlated with left ventricular mass index (LVMI; r=0.231, p=0.007). The UNa level was not linearly correlated with left ventricular structural parameters in patients with PA. To test if UNa has a non-linear relationship with LVMI among patients with PA, we categorized the participants according to the tertile of UNa (low, median, and high tertile). PA patients with medium tertile of UNa had significant lower LVMI than the other two groups (LVMI: 144.1 ± 42.9, 121.1 ± 33.4, and 136.7 ± 32.8 g/m2, from the lowest to the highest tertile of Una; analysis of variance p=0.006, post-hoc p <0.05). Multifactor analysis of variance confirmed this finding after adjustment for clinical parameters. Post-hoc analyses revealed that the high UNa tertile was associated with higher left ventricular end-diastolic volume compared with medium UNa tertile; while the low UNa tertile was associated with higher mean wall thickness compared with medium UNa tertile. The findings imply the reasons for increased LVMI may be different in patients with the highest and lowest UNa tertile. In conclusion, the medium tertile of 24-hour UNa is associated with lowest LVMI in patients with PA.

Medication Incidents Involving Antiepileptic Drugs in Canadian Hospitals: A Multi-Incident Analysis.

Medication errors involving antiepileptic drugs (AEDs) are not well studied but have the potential to cause significant harm. We investigated the occurrence of medication incidents in Canadian hospitals that involve AEDs, their severity and contributing factors by analyzing data from two national databases. Our multi-incident analysis revealed that while medication errors were rarely fatal, errors do occur of which some are serious. Medication incidents were most commonly caused by dose omissions, the dose or its frequency being incorrect and the wrong AED being given. Our analysis could augment quality-improvement initiatives by medication safety administrators to reduce AED medication incidents in hospitals.

Microarray meta-analysis to explore abiotic stress-specific gene expression patterns in Arabidopsis.

BACKGROUND: Abiotic stresses are the major limiting factors that affect plant growth, development, yield and final quality. Deciphering the underlying mechanisms of plants' adaptations to stresses using few datasets might overlook the different aspects of stress tolerance in plants, which might be simultaneously and consequently operated in the system. Fortunately, the accumulated microarray expression data offer an opportunity to infer abiotic stress-specific gene expression patterns through meta-analysis. In this study, we propose to combine microarray gene expression data under control, cold, drought, heat, and salt conditions and determined modules (gene sets) of genes highly associated with each other according to the observed expression data. RESULTS: By analyzing the expression variations of the Eigen genes from different conditions, we had identified two, three, and five gene modules as cold-, heat-, and salt-specific modules, respectively. Most of the cold- or heat-specific modules were differentially expressed to a particular degree in shoot samples, while most of the salt-specific modules were differentially expressed to a particular degree in root samples. A gene ontology (GO) analysis on the stress-specific modules suggested that the gene modules exclusively enriched stress-related GO terms and that different genes under the same GO terms may be alternatively disturbed in different conditions. The gene regulatory events for two genes, DREB1A and DEAR1, in the cold-specific gene module had also been validated, as evidenced through the literature search. CONCLUSIONS: Our protocols study the specificity of the gene modules that were specifically activated under a particular type of abiotic stress. The biplot can also assist to visualize the stress-specific gene modules. In conclusion, our approach has the potential to further elucidate mechanisms in plants and beneficial for future experiments design under different abiotic stresses.

The Ds1 Transposon Provides Messages That Yield Unique Profiles of Protein Isoforms and Acts Synergistically With Ds to Enrich Proteome Complexity via Exonization.

In exonization events, Ds1 may provide donor and/or acceptor sites for splicing after inserting into genes and be incorporated into new transcripts with new exon(s). In this study, the protein variants of Ds1 exonization yielding additional functional profile(s) were studied. Unlike Ds exonization, which creates new profiles mostly by incorporating flanking intron sequences with the Ds message, Ds1 exonization additionally creates new profiles through the presence or absence of Ds1 messages. The number of unique functional profiles harboring Ds1 messages is 1.3-fold more than that of functional profiles without Ds1 messages. The highly similar 11 protein isoforms at a single insertion site also contribute to proteome complexity enrichment by exclusively creating new profiles. Particularly, Ds1 exonization produces 459 unique profiles, of which 129 cannot be built by Ds. We thus conclude that Ds and Ds1 are independent but synergistic in their capacity to enrich proteome complexity through exonization.

5-methoxytryptophan is a potential marker for post-myocardial infarction heart failure - a preliminary approach to clinical utility.

BACKGROUND: Ventricular remodeling following myocardial infarction (MI) is closely associated with cyclooxygenase-2 (COX-2) expression. 5-methoxytryptophan (5-MTP) was reported to control COX-2 expression. OBJECTIVES: To investigeate the association between 5-MTP and post-MI left ventricular remodeling. METHODS: This prospective study enrolled 26 non-diabetic patients with first-time ST segment elevation myocardial infarction (STEMI), and 58 controls. Levels of 5-MTP, N-terminal of pro-brain natriuretic peptide (NT-proBNP), aminoterminal propeptide of type III procollagen, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 were measured at day 1, day 3, 3months, 6months, and 1year post-MI. Echocardiography was performed during the acute stage (within 72h) and 3months, 6months, and 1year post-MI. RESULTS: The STEMI patients had a significantly lower plasma 5-MTP level at day 1 which reached a nadir at 3months post-MI. The level of 5-MTP at day 3 post-MI was significantly correlated with the level of NT-proBNP 1year post-MI, suggesting that the level of plasma 5-MTP in the early phase after MI may predict subsequent cardiac stress and failure. Receiver operating characteristic curve analysis revealed that plasma 5-MTP had the best area under the curve value to predict plasma NT-proBNP 1year post-MI. Further analysis using net reclassification improvement and integrated discrimination improvement models confirmed that plasma 5-MTP at day 3 post-MI significantly improved the predictive power of each of the parameters. CONCLUSION: In non-diabetic STEMI patients, plasma 5-MTP levels were associated with biomarkers of post-MI left ventricular remodeling and damage.

Heart rhythm complexity impairment in patients undergoing peritoneal dialysis.

Cardiovascular disease is one of the leading causes of death in patients with advanced renal disease. The objective of this study was to investigate impairments in heart rhythm complexity in patients with end-stage renal disease. We prospectively analyzed 65 patients undergoing peritoneal dialysis (PD) without prior cardiovascular disease and 72 individuals with normal renal function as the control group. Heart rhythm analysis including complexity analysis by including detrended fractal analysis (DFA) and multiscale entropy (MSE) were performed. In linear analysis, the PD patients had a significantly lower standard deviation of normal RR intervals (SDRR) and percentage of absolute differences in normal RR intervals greater than 20 ms (pNN20). Of the nonlinear analysis indicators, scale 5, area under the MSE curve for scale 1 to 5 (area 1-5) and 6 to 20 (area 6-20) were significantly lower than those in the control group. In DFA anaylsis, both DFA α1 and DFA α2 were comparable in both groups. In receiver operating characteristic curve analysis, scale 5 had the greatest discriminatory power for two groups. In both net reclassification improvement model and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of SDRR, pNN20, and pNN50. In conclusion, PD patients had worse cardiac complexity parameters. MSE parameters are useful to discriminate PD patients from patients with normal renal function.

Identification of miRNAs and Their Targets in the Liverwort Marchantia polymorpha by Integrating RNA-Seq and Degradome Analyses.

Bryophytes (liverworts, hornworts and mosses) comprise the three earliest diverging lineages of land plants (embryophytes). Marchantia polymorpha, a complex thalloid Marchantiopsida liverwort that has been developed into a model genetic system, occupies a key phylogenetic position. Therefore, M. polymorpha is useful in studies aiming to elucidate the evolution of gene regulation mechanisms in plants. In this study, we used computational, transcriptomic, small RNA and degradome analyses to characterize microRNA (miRNA)-mediated pathways of gene regulation in M. polymorpha. The data have been integrated into the open access ContigViews-miRNA platform for further reference. In addition to core components of the miRNA pathway, 129 unique miRNA sequences, 11 of which could be classified into seven miRNA families that are conserved in embryophytes (miR166a, miR390, miR529c, miR171-3p, miR408a, miR160 and miR319a), were identified. A combination of computational and degradome analyses allowed us to identify and experimentally validate 249 targets. In some cases, the target genes are orthologous to those of other embryophytes, but in other cases, the conserved miRNAs target either paralogs or members of different gene families. In addition, the newly discovered Mpo-miR11707.1 and Mpo-miR11707.2 are generated from a common precursor and target MpARGONAUTE1 (LW1759). Two other newly discovered miRNAs, Mpo-miR11687.1 and Mpo-miR11681.1, target the MADS-box transcription factors MpMADS1 and MpMADS2, respectively. Interestingly, one of the pentatricopeptide repeat (PPR) gene family members, MpPPR_66 (LW9825), the protein products of which are generally involved in various steps of RNA metabolism, has a long stem-loop transcript that can generate Mpo-miR11692.1 to autoregulate MpPPR_66 (LW9825) mRNA. This study provides a foundation for further investigations of the RNA-mediated silencing mechanism in M. polymorpha as well as of the evolution of this gene silencing pathway in embryophytes.

A Stepwise Approach of Finding Dependent Variables via Coefficient of Intrinsic Dependence.

The coefficient of intrinsic dependence (CID) is capable of determining associations among variables without making distributional or functional assumptions regarding random variables. In this study, we developed the partial coefficient of intrinsic dependence (pCID) to facilitate the step-by-step selection of variables that are relevant to a target variable. The strategy of selecting relevant variables using the CID along with the pCID can eliminate interference from other relevant variables. From simulation results, we observed that the proposed method is more sensitive to curvilinearity and more specific to linearity than the combination of Pearsons correlation coefficient and the partial correlation coefficient (PCC/pPCC). This property may provide the opportunity to index different levels of curvilinearity according to CID/pCID outcomes. In practice trials conducted using publicly available microarray data, the CID/pCID procedure successfully identified cold-responsive genes related to three C-repeat binding factors, and was especially effective at identifying some sample-specific gene-gene interactions. Therefore, the proposed strategy may be beneficial in meta-analysis to distinguish general forms of relationships from the noise.

MicroRNA396-Targeted SHORT VEGETATIVE PHASE Is Required to Repress Flowering and Is Related to the Development of Abnormal Flower Symptoms by the Phyllody Symptoms1 Effector.

Leafy flowers are the major symptoms of peanut witches' broom (PnWB) phytoplasma infection in Catharanthus roseus. The orthologs of the phyllody symptoms1 (PHYL1) effector of PnWB from other species of phytoplasma can trigger the proteasomal degradation of several MADS box transcription factors, resulting in leafy flower formation. In contrast, the flowering negative regulator gene SHORT VEGETATIVE PHASE (SVP) was up-regulated in PnWB-infected C. roseus plants, but most microRNA (miRNA) genes had repressed expression. Coincidentally, transgenic Arabidopsis (Arabidopsis thaliana) plants expressing the PHYL1 gene of PnWB (PHYL1 plants), which show leafy flower phenotypes, up-regulate SVP of Arabidopsis (AtSVP) but repress a putative regulatory miRNA of AtSVP, miR396. However, the mechanism by which PHYL1 regulates AtSVP and miR396 is unknown, and the evidence of miR396-mediated AtSVP degradation is lacking. Here, we show that miR396 triggers AtSVP messenger RNA (mRNA) decay using genetic approaches, a reporter assay, and high-throughput degradome profiles. Genetic evidence indicates that PHYL1 plants and atmir396a-1 mutants have higher AtSVP accumulation, whereas the transgenic plants overexpressing MIR396 display lower AtSVP expression. The reporter assay indicated that target-site mutation results in decreasing the miR396-mediated repression efficiency. Moreover, degradome profiles revealed that miR396 triggers AtSVP mRNA decay rather than miRNA-mediated cleavage, implying that AtSVP caused miR396-mediated translation inhibition. We hypothesize that PHYL1 directly or indirectly interferes with miR396-mediated AtSVP mRNA decay and synergizes with other effects (e.g. MADS box transcription factor degradation), resulting in abnormal flower formation. We anticipate our findings to be a starting point for studying the posttranscriptional regulation of PHYL1 effectors in symptom development.