A Rare Case of a Primary Cardiac Tumor Presenting as Fatal Ventricular Tachycardia

Primary cardiac tumors are extremely uncommon. Here, we report the case of a patient with a primary left ventricular interstitial tumor presenting with hemodynamically unstable ventricular tachycardia. In response to hemodynamically unstable ventricular tachycardia, an implantable cardioverter-defibrillator was inserted. One month after defibrillator implantation, the patient developed episodes of high ventricular tachycardia that could not be effectively terminated by catheter radiofrequency ablation, thus further confirming that the ventricular tachycardia was induced by the left ventricular interstitial tumor. The patient is doing well on medical therapy to date

Synthesis and Characterization of Cobalt-Doped WS2 Nanorods for Lithium Battery Applications

Cobalt-doped tungsten disulfide nanorods were synthesized by an approach involving exfoliation, intercalation, and the hydrothermal process, using commercial WS2 powder as the precursor and n-butyllithium as the exfoliating reagent. XRD results indicate that the crystal phase of the sample is 2H-WS2. TEM images show that the sample consists of bamboo-like nanorods with a diameter of around 20 nm and a length of about 200 nm. The Co-doped WS2 nanorods exhibit the reversible capacity of 568 mAh g−1 in a voltage range of 0.01–3.0 V versus Li/Li+. As an electrode material for the lithium battery, the Co-doped WS2 nanorods show enhanced charge capacity and cycling stability compared with the raw WS2 powder

TaNAC2, a NAC-type wheat transcription factor conferring enhanced multiple abiotic stress tolerances in Arabidopsis

Environmental stresses such as drought, salinity, and cold are major factors that significantly limit agricultural productivity. NAC transcription factors play essential roles in response to various abiotic stresses. However, the paucity of wheat NAC members functionally characterized to date does not match the importance of this plant as a world staple crop. Here, the function of TaNAC2 was characterized in Arabidopsis thaliana. A fragment of TaNAC2 was obtained from suppression subtractive cDNA libraries of wheat treated with polyethylene glycol, and its full-length cDNA was obtained by searching a full-length wheat cDNA library. Gene expression profiles indicated that TaNAC2 was involved in response to drought, salt, cold, and abscisic acid treatment. To test its function, transgenic Arabidopsis lines overexpressing TaNAC2–GFP controlled by the cauliflower mosaic virus 35S promoter were generated. Overexpression of TaNAC2 resulted in enhanced tolerances to drought, salt, and freezing stresses in Arabidopsis, which were simultaneously demonstrated by enhanced expression of abiotic stress-response genes and several physiological indices. Therefore, TaNAC2 has potential for utilization in transgenic breeding to improve abiotic stress tolerances in crops

De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders

Congenital diaphragmatic hernia (CDH) is a severe birth defect that is often accompanied by other congenital anomalies. Previous exome sequencing studies for CDH have supported a role of de novo damaging variants but did not identify any recurrently mutated genes. To investigate further the genetics of CDH, we analyzed de novo coding variants in 362 proband-parent trios including 271 new trios reported in this study. We identified four unrelated individuals with damaging de novo variants in MYRF (P = 5.3x10-8), including one likely gene-disrupting (LGD) and three deleterious missense (D-mis) variants. Eight additional individuals with de novo LGD or missense variants were identified from our other genetic studies or from the literature. Common phenotypes of MYRF de novo variant carriers include CDH, congenital heart disease and genitourinary abnormalities, suggesting that it represents a novel syndrome. MYRF is a membrane associated transcriptional factor highly expressed in developing diaphragm and is depleted of LGD variants in the general population. All de novo missense variants aggregated in two functional protein domains. Analyzing the transcriptome of patient-derived diaphragm fibroblast cells suggest that disease associated variants abolish the transcription factor activity. Furthermore, we showed that the remaining genes with damaging variants in CDH significantly overlap with genes implicated in other developmental disorders. Gene expression patterns and patient phenotypes support pleiotropic effects of damaging variants in these genes on CDH and other developmental disorders. Finally, functional enrichment analysis implicates the disruption of regulation of gene expression, kinase activities, intra-cellular signaling, and cytoskeleton organization as pathogenic mechanisms in CDH

Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by pathogenic remodeling of pulmonary arterioles leading to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. PAH can be associated with other diseases (APAH: connective tissue diseases, congenital heart disease, and others) but often the etiology is idiopathic (IPAH). Mutations in bone morphogenetic protein receptor 2 (BMPR2) are the cause of most heritable cases but the vast majority of other cases are genetically undefined. METHODS: To identify new risk genes, we utilized an international consortium of 4241 PAH cases with exome or genome sequencing data from the National Biological Sample and Data Repository for PAH, Columbia University Irving Medical Center, and the UK NIHR BioResource - Rare Diseases Study. The strength of this combined cohort is a doubling of the number of IPAH cases compared to either national cohort alone. We identified protein-coding variants and performed rare variant association analyses in unrelated participants of European ancestry, including 1647 IPAH cases and 18,819 controls. We also analyzed de novo variants in 124 pediatric trios enriched for IPAH and APAH-CHD. RESULTS: Seven genes with rare deleterious variants were associated with IPAH with false discovery rate smaller than 0.1: three known genes (BMPR2, GDF2, and TBX4), two recently identified candidate genes (SOX17, KDR), and two new candidate genes (fibulin 2, FBLN2; platelet-derived growth factor D, PDGFD). The new genes were identified based solely on rare deleterious missense variants, a variant type that could not be adequately assessed in either cohort alone. The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. For pediatric PAH, predicted deleterious de novo variants exhibited a significant burden compared to the background mutation rate (2.45×, p = 2.5e-5). At least eight novel pediatric candidate genes carrying de novo variants have plausible roles in lung/heart development. CONCLUSIONS: Rare variant analysis of a large international consortium identified two new candidate genes-FBLN2 and PDGFD. The new genes have known functions in vasculogenesis and remodeling. Trio analysis predicted that ~ 15% of pediatric IPAH may be explained by de novo variants

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10−13), ALDH2/MYL2 (rs671, P = 3.40 × 10−11; rs12229654, P = 4.56 × 10−9), ITIH4 (rs2535633, P = 1.77 × 10−10) and NT5C2 (rs11191580, P = 3.83 × 10−8) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10−8) and an additional 14 at P < 1.0 × 10−3 with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity

Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH

Abstract: Background: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by pathogenic remodeling of pulmonary arterioles leading to increased pulmonary pressures, right ventricular hypertrophy, and heart failure. PAH can be associated with other diseases (APAH: connective tissue diseases, congenital heart disease, and others) but often the etiology is idiopathic (IPAH). Mutations in bone morphogenetic protein receptor 2 (BMPR2) are the cause of most heritable cases but the vast majority of other cases are genetically undefined. Methods: To identify new risk genes, we utilized an international consortium of 4241 PAH cases with exome or genome sequencing data from the National Biological Sample and Data Repository for PAH, Columbia University Irving Medical Center, and the UK NIHR BioResource – Rare Diseases Study. The strength of this combined cohort is a doubling of the number of IPAH cases compared to either national cohort alone. We identified protein-coding variants and performed rare variant association analyses in unrelated participants of European ancestry, including 1647 IPAH cases and 18,819 controls. We also analyzed de novo variants in 124 pediatric trios enriched for IPAH and APAH-CHD. Results: Seven genes with rare deleterious variants were associated with IPAH with false discovery rate smaller than 0.1: three known genes (BMPR2, GDF2, and TBX4), two recently identified candidate genes (SOX17, KDR), and two new candidate genes (fibulin 2, FBLN2; platelet-derived growth factor D, PDGFD). The new genes were identified based solely on rare deleterious missense variants, a variant type that could not be adequately assessed in either cohort alone. The candidate genes exhibit expression patterns in lung and heart similar to that of known PAH risk genes, and most variants occur in conserved protein domains. For pediatric PAH, predicted deleterious de novo variants exhibited a significant burden compared to the background mutation rate (2.45×, p = 2.5e−5). At least eight novel pediatric candidate genes carrying de novo variants have plausible roles in lung/heart development. Conclusions: Rare variant analysis of a large international consortium identified two new candidate genes—FBLN2 and PDGFD. The new genes have known functions in vasculogenesis and remodeling. Trio analysis predicted that ~ 15% of pediatric IPAH may be explained by de novo variants

Risk factors of thrombosis in Chinese subjects with acute promyelocytic leukemia

Abstract Background Acute promyelocytic leukemia (APL) is a special type of acute myeloid leukemia Thrombosis is at increased risk complication in patients with this disease. However, the risk factors of thrombosis related to Chinese APL patients are not fully understood. Methods In this study, clinical and laboratory data of 44 consecutively Chinese APL patients were collected and analyzed. Results One arterial and 6 venous thrombosis occurred in 44 patients, including 22 males and 22 females, with a median age of 44 years (range from 18 to 74 years). The ratio of male and female gender, age, white blood cell count, hemoglobin, platelets, disease risk stratification, CD2, Khorana score, differentiation syndrome (DS) and gene mutation related to prognosis of APL, including DNMT3A, TET2, IDH1, IDH2, NRAS and ASXL1 in the two groups with and without thrombosis were not statistically significant. The detection rate of PAI-1 genotype 4G4G was 71.4% (5/7) in 7 patients with thrombosis, while the detection rate of PAI-1 genotype 4G4G in 37 patients without thrombosis was 8.1% (3/37). The differences between the two groups in WT-1 (P = 0.01), PAI-1 4G4G (P = 0.0009), bcr3 (P = 0.027), CD15 (P = 0.005), and FLT3-ITD mutation (P = 0.0008) were statistically significant. Using multivariate analysis, the risk factors of venous thrombosis in APL were CD15 (P = 0.043), PAI-1 4G4G (P = 0.009), WT-1 (P = 0.043) and FLT3/ITD (P = 0.013), respectively. Conclusion Our results suggested the PAI-1 gene 4G4G type, CD15, WT-1 and FLT3-ITD mutations excluding DNMT3A, TET2, IDH1/2, NRAS and ASXL1 are risk factors of thrombotic events in Chinese APL patients

Overexpression of Nitrate Transporter <i>OsNRT2.1</i> Enhances Nitrate-Dependent Root Elongation

Root morphology is essential for plant survival. NO3&#8722; is not only a nutrient, but also a signal substance affecting root growth in plants. However, the mechanism of NO3&#8722;-mediated root growth in rice remains unclear. In this study, we investigated the effect of OsNRT2.1 on root elongation and nitrate signaling-mediated auxin transport using OsNRT2.1 overexpression lines. We observed that the overexpression of OsNRT2.1 increased the total root length in rice, including the seminal root length, total adventitious root length, and total lateral root length in seminal roots and adventitious roots under 0.5-mM NO3&#8722; conditions, but not under 0.5-mM NH4+ conditions. Compared with wild type (WT), the 15NO3&#8722; influx rate of OsNRT2.1 transgenic lines increased by 24.3%, and the expressions of auxin transporter genes (OsPIN1a/b/c and OsPIN2) also increased significantly under 0.5-mM NO3&#8722; conditions. There were no significant differences in root length, &#223;-glucuronidase (GUS) activity, and the expressions of OsPIN1a/b/c and OsPIN2 in the pDR5::GUS transgenic line between 0.5-mM NO3&#8722; and 0.5-mM NH4+ treatments together with N-1-naphthylphalamic acid (NPA) treatment. When exogenous NPA was added to 0.5-mM NO3&#8722; nutrient solution, there were no significant differences in the total root length and expressions of OsPIN1a/b/c and OsPIN2 between transgenic plants and WT, although the 15NO3&#8722; influx rate of OsNRT2.1 transgenic lines increased by 25.2%. These results indicated that OsNRT2.1 is involved in the pathway of nitrate-dependent root elongation by regulating auxin transport to roots; i.e., overexpressing OsNRT2.1 promotes an effect on root growth upon NO3&#8722; treatment that requires active polar auxin transport

Solvothermal synthesis of Mn2P2O7 and its application in lithium-ion battery

Manganese pyrophosphate, Mn2P2O7 was synthesized by a simple solvothermal method using Mn metal powder and P2S5 in ethylene glycol medium at 190–220 °C. Morphology and crystalline structure of the products were characterized by X-ray diffraction and scanning electron microscopy. The flower-like microspheres with diameters of about 2–5 μm are composed of a number of nanoplatelets with thickness of 20–40 nm. The effect of reaction temperature and reaction time on the microstructure of Mn2P2O7 was investigated. The samples were used as active anode materials for lithium-ion battery and their electrochemical properties were examined by constant current charge–discharge cycling. The Mn2P2O7 electrodes exhibited initial reversible capacities of 440–330 mAh g− 1 depending on the synthetic conditions. From these results, a possible reaction mechanism of Mn2P2O7 with lithium was proposed