A molecular basis behind heterophylly in an amphibious plant, Ranunculus trichophyllus.

Ranunculus trichophyllus is an amphibious plant that produces thin and cylindrical leaves if grown under water but thick and broad leaves if grown on land. We found that such heterophylly is widely controlled by two plant hormones, abscisic acid (ABA) and ethylene, which control terrestrial and aquatic leaf development respectively. Aquatic leaves produced higher levels of ethylene but lower levels of ABA than terrestrial leaves. In aquatic leaves, their distinct traits with narrow shape, lack of stomata, and reduced vessel development were caused by EIN3-mediated overactivation of abaxial genes, RtKANADIs, and accompanying with reductions of STOMAGEN and VASCULAR-RELATED NAC-DOMAIN7 (VDN7). In contrast, in terrestrial leaves, ABI3-mediated activation of the adaxial genes, RtHD-ZIPIIIs, and STOMAGEN and VDN7 established leaf polarity, and stomata and vessel developments. Heterophylly of R.trichophyllus could be also induced by external cues such as cold and hypoxia, which is accompanied with the changes in the expression of leaf polarity genes similar to aquatic response. A closely-related land plant R. sceleratus did not show such heterophyllic responses, suggesting that the changes in the ABA/ethylene signaling and leaf polarity are one of key evolutionary steps for aquatic adaptation.

MUN (MERISTEM UNSTRUCTURED), encoding a SPC24 homolog of NDC80 kinetochore complex, affects development through cell division in Arabidopsis thaliana.

Kinetochore, a protein super-complex on the centromere of chromosomes, mediates chromosome segregation during cell division by providing attachment sites for spindle microtubules. The NDC80 complex, composed of four proteins, NDC80, NUF2, SPC24 and SPC25, is localized at the outer kinetochore and connects spindle fibers to the kinetochore. Although it is conserved across species, functional studies of this complex are rare in Arabidopsis. Here, we characterize a recessive mutant, meristem unstructured-1 (mun-1), exhibiting an abnormal phenotype with unstructured shoot apical meristem caused by ectopic expression of the WUSCHEL gene in unexpected tissues. mun-1 is a weak allele because of the insertion of T-DNA in the promoter region of the SPC24 homolog. The mutant exhibits stunted growth, embryo arrest, DNA aneuploidy, and defects in chromosome segregation with a low cell division rate. Null mutants of MUN from TALEN and CRISPR/Cas9-mediated mutagenesis showed zygotic embryonic lethality similar to nuf2-1; however, the null mutations were fully transmissible via pollen and ovules. Interactions among the components of the NDC80 complex were confirmed in a yeast two-hybrid assay and in planta co-immunoprecipitation. MUN is co-localized at the centromere with HTR12/CENH3, which is a centromere-specific histone variant, but MUN is not required to recruit HTR12/CENH3 to the kinetochore. Our results support that MUN is a functional homolog of SPC24 in Arabidopsis, which is required for proper cell division. In addition, we report the ectopic generations of stem cell niches by the malfunction of kinetochore components.

Kinetic study on Michael-type reactions of ß-nitrostyrenes with cyclic secondary amines in acetonitrile: transition-state structures and reaction mechanism deduced from negative enthalpy of activation and analyses of LFERs.

A kinetic study is reported for the Michael-type reactions of X-substituted ß-nitrostyrenes (1a-j) with a series of cyclic secondary amines in MeCN. The plots of pseudo-first-order rate constant k(obsd) vs [amine] curve upward, indicating that the reactions proceed through catalyzed and uncatalyzed routes. The dissection of k(obsd) into Kk2 and Kk3 (i.e., the rate constants for the uncatalyzed and catalyzed routes, respectively) revealed that Kk3 is much larger than Kk2, implying that the reactions proceed mainly through the catalyzed route when [amine] > 0.01 M. Strikingly, the reactivity of ß-nitrostyrene (1g) toward piperidine decreases as the reaction temperature increases. Consequently, a negative enthalpy of activation is obtained, indicating that the reaction proceeds through a relatively stable intermediate. The Brønsted-type plots for the reactions of 1g are linear with ß(nuc) = 0.51 and 0.61, and the Hammett plots for the reactions of 1a-j are also linear with ρX = 0.84 and 2.10 for the uncatalyzed and catalyzed routes, respectively. The reactions are concluded to proceed through six-membered cyclic transition states for both the catalyzed and uncatalyzed routes. The effects of the substituent X on reactivity and factors influencing ß(nuc) and ρX obtained in this study are discussed.

Duplex ultrasound abnormalities of the lower limb veins might precede clinical venous reflux signs in post-Fontan adolescents and young adults.

OBJECTIVE: After the Fontan operation (ie, direct anastomosis of the caval veins to the pulmonary arteries, constituting right ventricular bypass circulation), high central venous pressure can lead to peripheral venous stasis and venous valvar insufficiency. We hypothesized that post-Fontan patients are at a higher risk of developing lower extremity venous lesions detectable using duplex ultrasound, even if clinical signs of chronic venous disease might not be evident. METHODS: A total of 87 transplantation-free survivors after the Fontan procedure who reached adolescence or young adulthood (current age, 15-30 years) participated in a leg vein duplex ultrasound study. The median age at the Fontan procedure, median age at the vein study, and median interval between the two were 3.65 years (interquartile range [IQR], 3.1-5.3 years), 21.7 years (IQR, 18.9-24.7 years), and 16.6 years (IQR, 14.9-19.4 years), respectively. Duplex ultrasound scanning was performed using a venous ultrasound imaging system (Logiq P7; GE Healthcare). The patients were categorized according to the presence of venous reflux (VR) in the superficial, deep, or perforating venous systems: no VR, superficial VR (SVR), deep VR (DVR), perforating VR (PVR), and a combination of multiple venous systems. Correlation of the duplex ultrasound-detected venous lesions with clinical severity using the modified CEAP (clinical, etiological, anatomical, pathophysiological) classification was analyzed using Spearman's correlation analysis. RESULTS: Leg pain was reported by 48 of 87 patients (55.2%). The duplex ultrasound findings for the cohort were no VR in 21 patients (24.1%), SVR in 22 (25.3%), isolated PVR in 21 (24.1%), and reflux of multiple venous systems in 23 patients, including SVR and PVR in 19, DVR and PVR in 1, and SVR, PVR, and DVR in 3 patients. Although the patients with advanced venous lesions detected by duplex ultrasound tended to have a higher CEAP clinical class (P < .001), VR of any venous system on duplex ultrasound was present even in patients with a lower CEAP clinical class. The CEAP clinical class was C0 for 66 patients (76%), and VR of any venous system was present on duplex ultrasound in 66 patients (76%). CONCLUSIONS: The prevalence of lower extremity venous lesions detected by duplex ultrasound is strikingly high in post-Fontan adolescents and young adults, and duplex ultrasound-detected venous abnormalities can precede clinical manifestations. Early detection and timely intervention for leg vein problems are mandatory for post-Fontan patients, especially for those considered to have risk factors for developing chronic lower extremity venous disease.

Association between the extent of diffusion restriction on brain diffusion-weighted imaging and neurological outcomes after an out-of-hospital cardiac arrest.

BACKGROUND: This study evaluated the association between the extent of diffusion restriction on brain diffusion-weighted imaging (DWI) and neurological outcomes in patients who underwent targeted temperature management (TTM) after an out-of-hospital cardiac arrest (OHCA). METHODS: Patients who underwent brain magnetic resonance imaging within 10 days of OHCA between 2012 and 2021 were analysed. The extent of diffusion restriction was described according to the modified DWI Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS). The 35 predefined brain regions were assigned a score if diffuse signal changes were concordantly present in DWI scans and apparent diffusion coefficient maps. The primary outcome was an unfavourable neurological outcome at 6 months. The sensitivity, specificity, and receiver operating characteristic (ROC) curves for the measured parameters were analysed. Cut-off values were determined to predict the primary outcome. The predictive cut-off DWI-ASPECTS was internally validated using five-fold cross-validation. RESULTS: Of the 301 patients, 108 (35.9%) had 6-month favourable neurological outcomes. Patients with unfavourable outcomes had higher whole-brain DWI-ASPECTS (median, 31 [26-33] vs. 0 [0-1], P < 0.001) than those with favourable outcomes. The area under the ROC curve (AUROC) of whole-brain DWI-ASPECTS was 0.957 (95% confidence interval [CI] 0.928-0.977). A cut-off value of ≥8 for unfavourable neurological outcomes had specificity and sensitivity of 100% (95% CI 96.6-100) and 89.6% (95% CI 84.4-93.6), respectively. The mean AUROC was 0.956. CONCLUSION: More extensive diffusion restriction on DWI-ASPECTS in patients with OHCA who underwent TTM was associated with 6-month unfavourable neurological outcomes. Running title: Diffusion restriction and neurological outcomes after cardiac arrest.

A novel variant of NPPC causes abnormal post-translational cleavage: A candidate gene for premature ovarian insufficiency.

OBJECTIVE: Premature ovarian insufficiency (POI) is a clinical disease that is diagnosed by the loss of ovarian function before the age of 40. Despite recent progress in molecular diagnosis, the genetic etiology of POI is not well established. The aim of this study is to reveal pathogenic genetic variants involved in POI. STUDY DESIGN AND MAIN OUTCOME MEASURES: To reveal pathogenic genetic variants involved in POI, whole exome sequencing was performed in nonconsanguineous family members with POI. Constitutional variants were filtered against population databases and a missense mutation of natriuretic peptide C (NPPC) (c.131A>G, p.Q44R) was selected as a convincing candidate mutation among 14 heterozygous mutant alleles in 13 genes. RESULTS: The wild-type NPPC and mutant NPPC (NPPC131A>G) were expressed in HeLa cells, and cells expressing NPPC131A>G secreted unique peptides. The ProP 1.0 Server, a neural network prediction tool, predicted the presence of a cleavage site at the substituted arginine residue (p.Q44R) of NPPC. The molecular weight of predicted cleaved peptides processed from mutant NPPC precursor corresponded to that of the actual mutant peptide. The cGMP synthetic activity of NPR2-expressing cells was significantly decreased by interaction with the mutant NPPC peptide compared with wild-type NPPC. CONCLUSIONS: The peptide generated by a rare mutation of NPPC might influence paracrine C-type natriuretic peptide (CNP)-mediated preantral follicle development and/or sustain meiotic arrest in oocytes. We therefore suggest that a mutation of the NPPC gene is involved in the pathogenesis of POI.

The Significance of Estimated Glomerular Filtration Rate for Predicting Mortality in Glyphosate Herbicide-Intoxicated Patients: A Single-Center, Retrospective Observational Study.

Background: Glyphosate herbicide (GH) is widely used worldwide. It has a higher fatality rate than expected. GH-poisoned cases are increasingly reported. Acute kidney injury in poisoned patients is one of several predictors of GH mortality. The aim of this study was to determine whether estimated glomerular filtration rate (eGFR) could predict kidney injury in GH intoxication. Methods: This was a retrospective study conducted at the emergency department (ED) of a single hospital between January 2004 and December 2021. A total of 434 patients presented with GH intoxication via oral ingestion, and 424 were enrolled. Their demographic characteristics, laboratory variables, complications, and mortality were analyzed to determine clinical predictors associated with GH-induced mortality using a logistic regression analysis. The relationship between GH intoxication and eGFR was determined based on the results of dominance analysis. Additionally, the comparison of creatinine and eGFR was performed through receiver operating characteristic (ROC) curves. Results: A total of 424 GH-poisoned patients were enrolled. Of them, 43 (10.1%) died. In the multivariable analysis, initial GCS (OR: 0.874; 95% CI: 0.765−0.998, p = 0.047), albumin (OR: 0.874; 95% CI: 0.765−0.998, p = 0.027), pH (OR: 0.002; 95% CI: 0.000−0.037, p < 0.001), QTc interval (OR: 1.018; 95% CI: 1.007−1.029, p = 0.001), and eGFR (OR: 0.969; 95% CI: 0.95−0.989, p = 0.003) were independent factors for predicting in-hospital mortality. In the dominance analysis of the relative importance of the predictive factors, pH accounted for the largest proportion at 35.8%, followed by QTc (20.0%), GCS (17.3%), eGFR (17.0%), and albumin (9.9%). Additionally, eGFR had a larger area under the ROC curve (0.846; 95% CI, 0.809−0.879) than that of creatinine (0.811; 95% CI, 0.771−0.848, p = 0.033). Conclusion: In sum, eGFR, considered a surrogate of renal function, was a useful prognostic factor for mortality in glyphosate herbicide-poisoned patients.

Author Correction: Comparative analysis of molecular and physiological traits between perennial Arabis alpina Pajares and annual Arabidopsis thaliana Sy-0.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Comparative analysis of molecular and physiological traits between perennial Arabis alpina Pajares and annual Arabidopsis thaliana Sy-0.

Annual plants complete life cycle in a year while perennial plants maintain growth for several years. Arabis alpina, a polycarpic perennial, is a close relative of monocarpic annual Arabidopsis. Pajares is an accession of A. alpina requiring vernalization, a long-term cold for flowering. Arabidopsis shows holistic flowering whereas Pajares shows idiographic flowering, producing axillary branches under variable developmental phases from juvenile, adult vegetative to reproductive phases. To understand the molecular mechanism behind diverse phases of axillary branches, we analyzed the levels of primary miR156 expressions because miR156-SPL module is a key regulator for developmental phase transition. We found that in Pajares, miR156 levels were highly variable among the axillary branches, which causes differential sensitivity to vernalization. Thus, the axillary branches expressing high levels of miR156 remain in juvenile phase even after vernalization, whereas the axillary branches expressing low levels of miR156 produce flowers after vernalization. In contrast, every axillary branches of Arabidopsis winter annual Sy-0 expressed similar levels of miR156 and synchronously responded to vernalization, which causes holistic flowering. Therefore, we suggest that variable miR156 expression levels and the resulting differential response to vernalization among axillary branches are distinctive features determining polycarpic perenniality of A. alpina Pajares.

Clinical Effect of Left Ventricular Dysfunction in Patients with Mitral Stenosis after Mitral Valve Replacement.

BACKGROUND: Mitral stenosis (MS) remains one of the important heart diseases. There are many factors that influence the clinical outcomes, and little is known about how left ventricular (LV) dysfunction clinically affects the prognosis of the patient with MS after mitral valve replacement (MVR). We reviewed our clinical experiences of MVR in patients with MS who had LV dysfunction. METHODS: Between January 1991 and January 2013, 110 patients with MS who underwent MVR were analyzed and divided into two groups according to ejection fraction (EF). Group 1 (EF≤45%) included 13 patients and group 2 (EF>45%) included 97 patients. RESULTS: Thromboembolism occurred in 8 patients after MVR (group 1: n=3, 23.1%; group 2: n=5, 5.2%) and its incidence was significantly higher in group 1 than in group 2 (p=0.014). There were 3 deaths each in groups 1 and 2 during follow-up. The overall rate of cardiac-related death in group 1 was significantly higher than in group 2 (group 1: n=3, 23.1%; group 2: n=3, 3.1%; p=0.007). The cumulative survival rate at 1 and 15 years was 83.9% and 69.9% in group 1 and 97.9% and 96.3% in group 2 (p=0.004). The Cox regression analysis revealed that survival was significantly associated with postoperative stroke (p=0.011, odds ratio=10.304). CONCLUSION: This study identified postoperative stroke as an adverse prognostic factor in patients with MS after MVR, and as more prevalent in patients with LV dysfunction. Postoperative stroke should be reduced to improve clinical outcomes for patients. Preventive care should be made in multiple ways, such as management of LV dysfunction, atrial fibrillation, and anticoagulation.

Associations among the Degree of Nonalcoholic Fatty Liver Disease, Metabolic Syndrome, Degree of Obesity in Children, and Parental Obesity.

PURPOSE: To analyze the associations among the degrees of nonalcoholic fatty liver disease (NAFLD) by ultrasonography and metabolic syndrome, degrees of obesity in children, and degrees of parental obesity. METHODS: A total of 198 children with obesity who visited a pediatric obesity clinic were prospectively enrolled in this study. The severity of NAFLD based on ultrasonography was classified into no, mild, moderate, or severe NAFLD group. The degree of obesity based on the percentage over standard weight for height per sex was classified into mild, moderate, or severe. RESULTS: Of 132 patients evaluated for the degree of NAFLD and metabolic syndrome, the p-value of correlation between the two factors was 0.009. Therefore, metabolic syndrome might significantly affect the degree of NAFLD. Of 158 patients evaluated for the degree of NAFLD and the degree of obesity, the p-value of correlation between the two factors was 0.122. Of 154 patients evaluated for the degree of obesity and father's obesity, the p-value was 0.076. Of 159 patients evaluated for the degree of obesity and mother's obesity, the p-value was 0.000, indicating that mother's obesity could significantly affect the degree of obesity in children. Of 142 patients evaluated for the degree of obesity and metabolic syndrome, the p-value was 0.288. CONCLUSION: Metabolic syndrome might significantly affect the degree of nonalcoholic fatty liver in children. In addition, mother's obesity might be a significant factor that affects the degree of obesity in children.

Malignant pheochromocytoma with lung metastasis after right adrenalectomy for pheochromocytoma eleven years ago.

A 30-year-old woman had multiple masses on right adrenalectomy site, posterior mediastinum, and left lung on computed tomography (CT) and positron emission tomography. She had a right adrenalectomy for pheochromocytoma eleven years ago. She received proper alpha and beta blocker and completed surgical resection. Pheochromocytoma was confirmed by histopathology. Here we report the case of metastatic malignant pheochromocytoma with very poor prognosis.

Visceral debranching thoracic endovascular aneurysm repair for chronic dissecting thoracoabdominal aortic aneurysm.

Type II chronic dissecting thoracoabdominal aortic aneurysms are a surgically challenging disease. The conventional thoracoabdominal aortic aneurysm repair technique using cardiopulmonary bypass is a high-risk procedure. However, a recently developed endovascular technique may be an alternative treatment for the disease, but faces the obstacle of lesional restriction. This new technique uses a hybrid strategy to overcome the limits of endovascular thoracoabdominal aortic aneurysm repair. Herein, we report on a successful outcome after performing the hybrid visceral debranching procedure.

Left atrial myxoma presenting with unusual cystic form.

Cardiac myxomas are the most common primary benign tumors of uncertain etiology. They usually present as polypoid or oval-shaped masses projecting into a heart chamber from the interatrial septum and have a soft, gelatinous consistency without a cystic structure. We report a case of left atrial myxoma with a single cystic form.

Outcomes of Mitral Valve Repair: Quadrangular Resection versus Chordal Replacement.

BACKGROUND: Mitral valve repair for posterior mitral leaflet (PML) prolapse has been considered to be a standard treatment because of its high success rate and high level of patient satisfaction. The aim of this study was to evaluate the clinical results of two different techniques of PML prolapse, quadrangular resection (QR) and chordal replacement (CR). MATERIALS AND METHODS: The subjects consisted of 56 patients who had undergone mitral valve repair for PML prolapse between November 1997 and December 2010. The patients were divided into two groups according to surgical technique. Among them, 31 patients underwent QR (group QR) and 25 patients had CR (group CR). We reviewed the medical records of the patients retrospectively to compare the clinical outcomes of both groups. RESULTS: After mitral valve repair, the degree of mitral regurgitation (MR) in both groups decreased to the to a mild degree or less and the amount of remnant MR was slightly higher in the CR group but it was not statistically different. Three patients received mitral valve-related reoperation (2 in the QR group and 1 in the CR group). Freedom from mitral valve-related reoperation at 7 years was 93% for the QR group and 96% for the CR group and was not significantly different between the two groups. CONCLUSION: Both QR and CR showed excellent long-term results and were considered equally effective methods for PML prolapse.