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Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Background: Obstructive sleep apnea (OSA) is a risk factor for atrial fibrillation (AF); however, it is unclear whether AF increases the risk of OSA. Furthermore, sex differences among patients with both AF and OSA remain unclear. We aimed to determine the association between an increased AF burden and OSA and investigate the differences in clinical characteristics between women and men with AF and OSA. Methods: This was a descriptive, cross-sectional analysis from a prospective cohort study. Patients with non-valvular AF were recruited from the cardiac electrophysiology clinic of a tertiary center; they underwent a home sleep apnea test and 14-day ambulatory electrocardiography. Moderate-to-severe OSA was defined as an apnea-hypopnea index of ≥15. Results: Of 320 patients with AF, 53.4% had moderate-to-severe OSA, and the mean body mass index (BMI) was 25.6 kg/m2. Less women (38.2%) had moderate-to-severe OSA than men (59.3%) (p

IntroductionSuperior vena cava (SVC) isolation has been proposed as part of the ablation strategy for atrial fibrillation. However, circumferential isolation of the SVC can lead to late-onset complications, such as SVC stenosis.MethodsWe describe a detailed observation of the SVC conduction pattern and present a newly developed approach for SVC isolation that involves creating a C-shaped non-circumferential ablation line while sparing the lateral segment.ResultsTwelve consecutive patients were included in the study, all of whom achieved bidirectional block during the ablation procedure.DiscussionThis approach to SVC isolation is effective and has the potential to reduce ablation related complications; however, larger studies and long-term follow-up is warranted to confirm these findings.

Though Berberis (Berberidaceae) is widely distributed across the Eurasian landmass it is most diverse in the Himalaya–Hengduan Mountain (HHM) region. There are more than 200 species in China where it is one of the most common mountain shrubs. The study on the taxonomy and evolution of Berberis in this region can thus provide an important insight into the origin and diversification of its flora. A prerequisite to this is mapping and describing the various species of Berberis in the region – a task that despite recent progress is by no means complete. It is clear that in China there may be a significant number of species still to be described and that even with published species much about their distribution remains to be discovered. As a contribution to the first of these tasks seven new species from the northern Hengduan Mountain of N. Sichuan and S. Qinghai: Berberis chinduensis, Berberis degexianensis, Berberis jiajinshanensis, Berberis jinwu, Berberis litangensis, Berberis longquensis and Berberis riparia, are described here. Differences in overall morphology and especially in floral structures with each other and with similar species of Berberis in the same region are presented. The report is the result of phylogenetic analyses based on plastome and partial nrDNA sequences of both the seven proposed new species and a significant number of similar species already published. Provisional conclusions as to the insights provides on the history of the genetic divergence are discussed.

Background: Thoracic aortic aneurysm and dissection (TAAD) is a devastating but treatable disease if detected early. The clinical manifestations and genetic characteristics underlying TAAD patients in Taiwan, however, remain unclear. Methods: We consecutively recruited patients referred for TAAD screening and/or management at a tertiary medical center in Taiwan. All patients received a comprehensive survey of the clinical manifestations and a genetic testing with a 29-gene next-generation sequencing (NGS) panel. Results: Patients (n = 107) were referred for different reasons, and could be grouped into 4 categories: known aortic aneurysm or dissection (AoAD) (n = 57), Marfanoid features (n = 36), having family members of suspected AoAD (n = 11), and ectopic lens (n = 3). AoAD were confirmed in 73 (68.2%) of the entire cohort. Among all the clinical manifestations, skin striae distensae was the only physical sign that showed significant association with AoAD (p = 0.007 after adjusted). Disease-causing genes/variants were identified in 46 patients (43.0%); FBN1 was the most prevalent disease-causing gene, followed by TGFBR1, TGFBR2 and FBN2. A positive genetic testing was not only an independent predictor of AoAD (hazard ratio (HR) 3.468, 95% confidence interval (CI) [1.541–7.807], p = 0.003), but also had a higher chance of dissection among the patients with known dilated aorta (HR 4.552, 95% CI [1.578–13.135], p = 0.005). Conclusion: The presence of skin striae distensae may serve as a clinical cue for physicians to search for AoAD in subjects who are at risk. The NGS panel test not only helps confirm the diagnosis, but also stratify the risk of dissection among patients with dilated aorta.

Abstract This study aimed to evaluate whether quantitative analysis of wrist photoplethysmography (PPG) could detect atrial fibrillation (AF). Continuous electrocardiograms recorded using an electrophysiology recording system and PPG obtained using a wrist-worn smartwatch were simultaneously collected from patients undergoing catheter ablation or electrical cardioversion. PPG features were extracted from 10, 25, 40, and 80 heartbeats of the split segments. Machine learning with a support vector machine and random forest approach were used to detect AF. A total of 116 patients were evaluated. We annotated > 117 h of PPG. A total of 6475 and 3957 segments of 25-beat pulse-to-pulse intervals (PPIs) were annotated as AF and sinus rhythm, respectively. The accuracy of the 25 PPIs yielded a test area under the receiver operating characteristic curve (AUC) of 0.9676, which was significantly better than the AUC for the 10 PPIs (0.9453; P

As biodiversity loss continues, there is an urgent need to develop efficient conservation measures to protect diversity with limited conservation resources. Conservation targets have generally been selected based on their population size, but more detailed assessments clarifying the phylogenetic genetic status, history, and phylogenetic uniqueness of rare species is crucial to set more appropriate and effective conservation measures. In Japan, the Act on Conservation of Endangered Species of Wild Fauna and Flora designated endangered plants with high conservation priority, but >40% of these species also grow overseas. We conducted comparative analyses based on ddRADseq and MIG-seq to evaluate the population conservation status and value of Vaccinium emarginatum and Elatostema platyphyllum which are growing across national borders at the eastern edge of their species distribution range. The analyses revealed contrasting conservation status between the two species; the Japanese population of V. emarginatum had lower genetic diversity at the individual level and phylogenetically differentiated from Taiwanese populations, while that of E. platyphyllum had higher diversity at the individual level and is a relatively recent migrant with little phylogenetical differentiation from Taiwanese populations. The two species, which share the common feature of being critically rare in Japan, showed contrasting genetic/phylogenetic characteristics. This study provided useful information for appropriate conservation measures based on species’ phylogenetic traits and genetic diversity.

Abstract Decision-making is considered an important aspect of cognitive function. Impaired decision-making is a consequence of cognitive decline caused by various physiological conditions, such as aging and neurodegenerative diseases. Here we exploited the value-based feeding decision (VBFD) assay, which is a simple sensory–motor task, to determine the cognitive status of Drosophila. Our results indicated the deterioration of VBFD is notably correlated with aging and neurodegenerative disorders. Restriction of the mushroom body (MB) neuronal activity partly blunted the proper VBFD. Furthermore, using the Drosophila polyQ disease model, we demonstrated the impaired VBFD is ameliorated by the dinitrosyl iron complex (DNIC-1), a novel and steady nitric oxide (NO)-releasing compound. Therefore we propose that the VBFD assay provides a robust assessment of Drosophila cognition and can be used to characterize additional neuroprotective interventions.

Abstract Lifespan is modulated at distinct levels by multiple factors, including genetic backgrounds, the environment, behavior traits, metabolic status, and more interestingly, sensory perceptions. However, the effects of social perception between individuals living in the same space remain less clear. Here, we used the Drosophila model to study the influences of social perception on the lifespan of aged fruit flies. We found the lifespan of aged Drosophila is markedly prolonged after being co-housed with young adults of the same gender. Moreover, the changes of lifespan were affected by several experimental contexts: (1) the ratios of aged and young adults co-housed, (2) the chronological ages of two populations, and (3) the integrity of sensory modalities. Together, we hypothesize the chemical/physical stimuli derived from the interacting young adults are capable of interfering with the physiology and behavior of aged flies, ultimately leading to the alteration of lifespan.

Abstract The accuracy of expansion microscopy (ExM) depends on the structural preservation of samples embedded in a hydrogel. However, it has been unknown to what extent gel embedding alters the molecular positions of individual labeled sites. Here, we quantified the accuracy of gel embedding by using stochastic optical reconstruction microscopy (STORM) to image DNA origami with well-defined structures. We found that embedding in hydrogels based on polyacrylamide, the most widely used chemistry in ExM, resulted in random displacements of labeled sites with a standard deviation of ~ 16 nm. In contrast, we found that embedding in tetra-gel, a hydrogel that does not depend on free-radical chain-growth polymerization, preserved labeled sites with a standard deviation of less than 5 nm. By combining tetra-gel ExM with STORM, we were able to resolve 11-nm structural features without the loss in accuracy seen with polyacrylamide gels. Our study thus provides direct measurements of the single-molecule distortions resulting from hydrogel embedding, and presents a way to improve super-resolution microscopy through combination with tetra-gel ExM.

Abstract Background Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (T2DM). Glycemic variability (GV) is associated with risk of micro- and macrovascular diseases. However, whether the GV can increase the risk of AF remains unknown. Methods The cohort study used a database from National Taiwan University Hospital, a tertiary medical center in Taiwan. Between 2014 and 2019, a total of 27,246 adult patients with T2DM were enrolled for analysis. Each individual was assessed to determine the coefficients of variability of fasting glucose (FGCV) and HbA1c variability score (HVS). The GV parameters were categorized into quartiles. Multivariate Cox regression models were employed to estimate the relationship between the GV parameters and the risk of AF, transient ischemic accident (TIA)/ischemic stroke and mortality in patients with T2DM. Results The incidence rates of AF and TIA/ischemic stroke were 21.31 and 13.71 per 1000 person-year respectively. The medium follow-up period was 70.7 months. In Cox regression model with full adjustment, the highest quartile of FGCV was not associated with increased risk of AF [Hazard ratio (HR): 1.12, 95% confidence interval (CI) 0.96–1.29, p = 0.148] or TIA/ischemic stroke (HR: 1.04, 95% CI 0.83–1.31, p = 0.736), but was associated with increased risk of total mortality (HR: 1.33, 95% CI 1.12–1.58, p

With about 153 species, the genus Androsace (Primulaceae) is known for its horticultural and economic importance. In this study, we report the complete chloroplast genome of Androsace erecta Maximowicz, a morphologically distinct species of Sect. Orthocaulon native to the Western China. The plastome of A. erecta is highly conserved in genome size, structure, and content when compared to all previously published plastomes of the genus. The phylogenomic analysis strongly supported A. erecta as sister to a clade comprising species of Sections Aizoideia and Chamaejasme. Lastly, we selected the four most variable regions across the Androsace species plastomes (trnKUUU-rps16, trnSGCU-trnGUCC, psbE-petL, and infA-rps8), which were considered to be suitable candidate DNA barcodes for Androsace.

We re-examined the taxonomic status of plants treated as Sedum formosanum (Crassulaceae) from Miyako-jima Island of the Ryukyu Islands, Japan, using morphological comparison and molecular phylogenetic analyses with related species. In morphology, plants from Miyako-jima Island bore a close resemblance to the other plants of S. formosanum, but differed in being perennial, polycarpic, and having lateral axillary branches. Molecular analyses based on ITS of nrDNA and six regions of cpDNA sequencing indicated that the Miyako-jima plants formed a distinct subclade. This subclade was part of a polytomy with three other subclades comprising nine taxa endemic to Taiwan and S. formosanum from other areas, including the type locality. Therefore, we propose and describe the Miyako-jima plants as a new subspecies, Sedum formosanum subsp. miyakojimense.

The early-diverging eudicot family Berberidaceae is composed of a morphologically diverse assemblage of disjunctly distributed genera long praised for their great horticultural and medicinal values. However, despite century-long studies, generic delimitation of Berberidaceae remains controversial and its tribal classification has never been formally proposed under a rigorous phylogenetic context. Currently, the number of accepted genera in Berberidaceae ranges consecutively from 13 to 19, depending on whether to define Berberis, Jeffersonia, and Podophyllum broadly, or to segregate these three genera further and recognize Alloberberis, Mahonia, and Moranothamnus, Plagiorhegma, and Dysosma, Diphylleia, and Sinopodophyllum, respectively. To resolve Berberidaceae’s taxonomic disputes, we newly assembled 23 plastomes and, together with 85 plastomes from the GenBank, completed the generic sampling of the family. With 4 problematic and 14 redundant plastome sequences excluded, robust phylogenomic relationships were reconstructed based on 93 plastomes representing all 19 genera of Berberidaceae and three outgroups. Maximum likelihood phylogenomic relationships corroborated with divergence time estimation support the recognition of three subfamilies Berberidoideae, Nandinoideae, and Podophylloideae, with tribes Berberideae and Ranzanieae, Leonticeae and Nandineae, and Podophylleae, Achlydeae, Bongardieae tr. nov., Epimedieae, and Jeffersonieae tr. nov. in the former three subfamilies, respectively. By applying specifically stated criteria, our phylogenomic data also support the classification of 19 genera, recognizing Alloberberis, Mahonia, and Moranothamnus, Plagiorhegma, and Diphylleia, Dysosma, and Sinopodophyllum that are morphologically and evolutionarily distinct from Berberis, Jeffersonia, and Podophyllum, respectively. Comparison of plastome structures across Berberidaceae confirms inverted repeat expansion in the tribe Berberideae and reveals substantial length variation in accD gene caused by repeated sequences in Berberidoideae. Comparison of plastome tree with previous studies and nuclear ribosomal DNA (nrDNA) phylogeny also reveals considerable conflicts at different phylogenetic levels, suggesting that incomplete lineage sorting and/or hybridization had occurred throughout the evolutionary history of Berberidaceae and that Alloberberis and Moranothamnus could have resulted from reciprocal hybridization between Berberis and Mahonia in ancient times prior to the radiations of the latter two genera.

While the genome sizes of flowering plants vary c. 2400-fold, it remains little known what factors may have driven the variation. In this study, we investigated the spatial pattern of the genome size of 54 populations of Acanthocalyx, which is found in the Hengduan-Himalaya Mountains. Our results showed that the red-flowered lineage of Acanthocalyx had significantly larger genomes (ranging from 1.9 to 2.5 Gb) compared to the white-flowered lineage, which had an average genome size of 1.27 Gb. This difference in genome size can be attributed to particular environmental factors. Within the red-flowered lineage, the genome size was positively correlated with soil nitrogen content and mean diurnal range. On the other hand, the genome size of the whiteflowered lineage, Acanthocalyx alba was negatively correlated with latitude which aligns with the population dynamics of this species during the Pleistocene. Overall, our findings highlight the influence of abiotic factors and geography in regulating the genome size of Acanthocalyx species. This study contributes to our understanding of the evolution of alpine plants in the Hengduan-Himalaya Mountains. [ABSTRACT FROM AUTHOR]

Background: Brugada syndrome (BrS) is a rare inherited disease causing sudden cardiac death (SCD). Copy number variants (CNVs) can contribute to disease susceptibility, but their role in Brugada syndrome (BrS) is unknown. We aimed to identify a CNV associated with BrS and elucidated its clinical implications. Methods: We enrolled 335 unrelated BrS patients from 2000 to 2018 in the Taiwanese population. Microarray and exome sequencing were used for discovery phase whereas Sanger sequencing was used for the validation phase. HEK cells and zebrafish were used to characterize the function of the CNV variant. Findings: A copy number deletion of GSTM3 (chr1:109737011-109737301, hg38) containing the eighth exon and the transcription stop codon was observed in 23.9% of BrS patients versus 0.8% of 15,829 controls in Taiwan Biobank (P < 0.001), and 0% in gnomAD. Co-segregation analysis showed that the co-segregation rate was 20%. Patch clamp experiments showed that in an oxidative stress environment, GSTM3 down-regulation leads to a significant decrease of cardiac sodium channel current amplitude. Ventricular arrhythmia incidence was significantly greater in gstm3 knockout zebrafish at baseline and after flecainide, but was reduced after quinidine, consistent with clinical observations. BrS patients carrying the GSTM3 deletion had higher rates of sudden cardiac arrest and syncope compared to those without (OR: 3.18 (1.77–5.74), P

Summary: Several studies have shown the beneficial effect of renal denervation (RDN) in the treatment of ventricular arrhythmia, especially in the setting of heart failure (HF). However, the underlying mechanism of antiarrhythmic effect of RDN is unknown. Arrhythmogenic cardiac alternans, particularly spatially discordant repolarization alternans, characterized by simultaneous prolongation and shortening of action potential duration (APD) in different myocardial regions, is central to the genesis of ventricular fibrillation in HF. Whether RDN decreases the susceptibility to arrhythmogenic cardiac alternans in HF has never been addressed before. The authors used a rat model of post-myocardial infarction HF and dual voltage-calcium optical mapping to investigate whether RDN could attenuate arrhythmogenic cardiac alternans that predisposes to ventricular arrhythmias, as well as the hemodynamic effect of RDN in HF. The HF rats had increased body weights, dilated hearts, and lower blood pressure. The HF rats also had longer ventricular APDs and a delay in the decay of the calcium transient, typical electrophysiological features of human HF. Susceptibility to calcium transient alternans, APD alternans, and spatially discordant APD alternans was increased in the HF hearts. RDN significantly attenuated a delay in the decay of the calcium transient, calcium transient and APD alternans, and importantly, the discordant APD alternans, and thereby decreased the incidence of induced ventricular arrhythmia in HF. RDN did not further decrease blood pressure in HF rats. In conclusion, RDN improves calcium cycling and prevents spatially discordant APD alternans and ventricular arrhythmia in HF. RDN does not aggravate hemodynamics in HF. Key Words: alternans, arrhythmia mechanism, heart failure, renal denervation

Tsai et al. here utilize a multi-stage genome-wide association study in Taiwanese population to show a copy number variation in the intron of potassium interacting channel 1 gene (KCNIP1) to be strongly associated with atrial fibrillation. The study also examines the functionality of KCNIP1 in heart electrophysiological function using cultured myocytes and zebrafish.

Brugada syndrome (BrS) is a hereditable sudden cardiac death (SCD). Mutations in the SCN5A gene (the most common BrS-causing gene) are responsible for 20–25% of this disease in Caucasian populations. However, the prevalence of SCN5A mutations in patients with BrS in the Chinese Han population in Taiwan remains unknown. Therefore, in this study, we investigated the prevalence of the SCN5A mutation in the largest BrS cohort in Taiwan. Methods: We consecutively enrolled 47 unrelated patients with BrS from medical centers and hospitals in Taiwan between 2000 and 2010. Mutations within all the 27 translated exons, and exon–intron boundaries of the SCN5A-encoded cardiac sodium channel were screened in all patients with BrS using direct sequencing. A total of 500 unrelated healthy volunteers with a normal electrocardiogram were genotyped as a control group. Results: SCN5A genetic variants were identified in 14 of the 47 patients with BrS and four of the 14 patients with BrS had missense mutations (1651 G>A, 1776 C>G, 3578 G>A). The prevalence rate of SCN5A mutations was approximately 8% (4/47), which was significantly lower than that reported in Caucasian populations (20–25%; p = 0.0007). The average age of these 14 BrS patients with SCN5A variants at diagnosis (12 men and 2 women) was 40 ± 13 years. Four patients experienced SCD, and six presented with seizure or syncope. Only three patients (3/14, 21.4%) had a family history of SCD. Conclusion: The prevalence of SCN5A mutations in the Chinese Han population in Taiwan may be lower than that reported in the Caucasian populations. In addition, most patients with BrS did not have a family history of SCD.

The roundworm C. elegans is a mainstay of aging research due to its short lifespan and easily manipulable genetics. Current, widely used methods for long-term measurement of C. elegans are limited by low throughput and the difficulty of performing longitudinal monitoring of aging phenotypes. Here we describe the WorMotel, a microfabricated device for long-term cultivation and automated longitudinal imaging of large numbers of C. elegans confined to individual wells. Using the WorMotel, we find that short-lived and long-lived strains exhibit patterns of behavioral decline that do not temporally scale between individuals or populations, but rather resemble the shortest and longest lived individuals in a wild type population. We also find that behavioral trajectories of worms subject to oxidative stress resemble trajectories observed during aging. Our method is a powerful and scalable tool for analysis of C. elegans behavior and aging.

Plasma gelsolin (pGSN) produced by muscle is an abundant protein of extracellular fluids capable of severing actin filaments and eliminating actin from the circulation. Additionally, pGSN modulates the cellular effects of some bioactive lipids. In this study we test the hypothesis that hormonal and metabolic adaptations to exercise are associated with changes in gelsolin concentration in blood. Plasma samples were collected from twenty healthy males recruited from untrained (UT, n=10) and endurance trained (ET, n=10) groups that performed 30-60 minutes of exercise on a cycloergometer at a workload corresponding to 700of VO2max. Gelsolin concentration was determined by quantitative Western blot analysis with an anti-human gelsolin antibody. The gelsolin concentration in UT and ET subjects before starting exercise ranged from 104 to 330 and 163 to 337 µg•ml-1 respectively. After 30 minutes of exercise we observed a significant decrease of plasma gelsolin in the UT group (p

Background/Purpose: Desmosome gene mutations have been reported in patients with arrhythmogenic right ventricular dysplasia (ARVD). However, there are hardly any genetic studies in Asians. We studied the clinical characteristics, cardiac manifestations and desmosome gene mutations in ARVD patients in Taiwan. Methods: Medical records of five ARVD patients were reviewed and genomic DNA was obtained from peripheral blood samples. Mutation screening in desmoplakin (DSP), plakophilin-2, desmoglein-2 (DSG2) and desmocollin-2 genes was performed using polymerase chain reaction and DNA sequencing techniques. Results: Among the five patients, three presented with palpitations followed by loss of consciousness, and the other two had palpitations or chest tightness without loss of consciousness. Electrocardiogram (ECG), magnetic resonance imaging and signal averaged ECG results were similar to those reported in Western countries. Mutations in the desmosome genes were identified in four of the five patients (three with a DSG2 mutation and one with a DSP mutation). Five gene mutations were noted in four patients and all mutations were novel (one patient had a DSG2 double mutation). The mutation types were missense in four and splicing mutation in one. Conclusion: Patients with ARVD in Taiwan had similar clinical and cardiac manifestations as reported in the Western literature. More than half of the patients had desmosome gene mutations.

While overexpression of TGFα has been reported in human pancreatic ductal adenocarcinoma (PDAC), mice with overexpressed TGFα develop premalignant pancreatic acinar-to-ductal metaplasia (ADM) but not PDAC. TGF-β signaling pathway is pivotal to the development of PDAC and tissue fibrosis. Here we sought to investigate the interplay between TGFα and TGF-β signaling in pancreatic tumorigenesis and fibrosis, namely via Smad4 inactivation.The MT-TGFα mouse was crossed with a new Smad4 conditional knock-out mouse (Smad4flox/flox;p48-Cre or S4) to generate Smad4flox/flox;MT-TGFα;p48-Cre (STP). After TGFα overexpression was induced with zinc sulfate water for eight months, the pancreata of the STP, MT-TGFα, and S4 mice were examined for tumor development and fibrotic responses. PanIN lesions and number of ducts were counted, and proliferation was measured by Ki67 immunohistochemistry (IHC). Qualitative analysis of fibrosis was analyzed by Trichrome Masson and Sirius Red staining, while vimentin was used for quantification. Expression analyses of fibrosis, pancreatitis, or desmoplasia associated markers (α-SMA, Shh, COX-2, Muc6, Col1a1, and Ctgf) were performed by IHC and/or qRT-PCR.Our STP mice exhibited advanced ADM, increased fibrosis, increased numbers of PanIN lesions, overexpression of chronic pancreatitis-related marker Muc6, and elevated expression of desmoplasia-associated marker Col1A1, compared to the MT-TGFα mice. The inactivation of Smad4 in the exocrine compartment was responsible for both the enhanced PanIN formation and fibrosis in the pancreas. The phenotype of the STP mice represents a transient state from ADMs to PanINs, closely mimicking the interface area seen in human chronic pancreatitis associated with PDAC.We have documented a novel mouse model, the STP mice, which displayed histologic presentations reminiscent to those of human chronic pancreatitis with signs of early tumorigenesis. The STP mice could be a suitable animal model for interrogating the transition of chronic pancreatitis to pancreatic cancer.

Apamin is commonly used as a small-conductance Ca2+-activated K+ (SK) current inhibitor. However, the specificity of apamin in cardiac tissues remains unclear.To test the hypothesis that apamin does not inhibit any major cardiac ion currents.We studied human embryonic kidney (HEK) 293 cells that expressed human voltage-gated Na+, K+ and Ca2+ currents and isolated rabbit ventricular myocytes. Whole-cell patch clamp techniques were used to determine ionic current densities before and after apamin administration.Ca2+ currents (CACNA1c+CACNB2b) were not affected by apamin (500 nM) (data are presented as median [25th percentile;75th percentile] (from -16 [-20;-10] to -17 [-19;-13] pA/pF, P = NS), but were reduced by nifedipine to -1.6 [-3.2;-1.3] pA/pF (p = 0.008). Na+ currents (SCN5A) were not affected by apamin (from -261 [-282;-145] to -268 [-379;-132] pA/pF, P = NS), but were reduced by flecainide to -57 [-70;-47] pA/pF (p = 0.018). None of the major K+ currents (IKs, IKr, IK1 and Ito) were inhibited by 500 nM of apamin (KCNQ1+KCNE1, from 28 [20]; [37] to 23 [18]; [32] pA/pF; KCNH2+KCNE2, from 28 [24]; [30] to 27 [24]; [29] pA/pF; KCNJ2, from -46 [-48;-40] to -46 [-51;-35] pA/pF; KCND3, from 608 [505;748] to 606 [454;684]). Apamin did not inhibit the INa or ICaL in isolated rabbit ventricular myocytes (INa, from -67 [-75;-59] to -68 [-71;-59] pA/pF; ICaL, from -16 [-17;-14] to -14 [-15;-13] pA/pF, P = NS for both).Apamin does not inhibit human cardiac Na+ currents, L-type Ca2+ currents or other major K+ currents. These findings indicate that apamin is a specific SK current inhibitor in hearts as well as in other organs.

Apamin sensitive potassium current (I KAS), carried by the type 2 small conductance Ca(2+)-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles.To test the hypothesis that amiodarone inhibits I KAS in human embryonic kidney 293 (HEK-293) cells.We used the patch-clamp technique to study I KAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration.Amiodarone inhibited IKAS in a dose-dependent manner (IC50, 2.67 ± 0.25 µM with 1 µM intrapipette Ca(2+)). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6 ± 3.1% of IKAS induced with 1 µM intrapipette Ca(2+) (n = 3). IKAS inhibition by amiodarone was not voltage-dependent, but was Ca(2+)-dependent: 30 µM amiodarone inhibited 81.5±1.9% of I KAS induced with 1 µM Ca(2+) (n = 4), and 16.4±4.9% with 250 nM Ca(2+) (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca(2+) dependent inhibition of I KAS.Both amiodarone and desethylamiodarone inhibit I KAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca(2+) concentration. SK2 current inhibition may in part underlie amiodarone's effects in preventing electrical storm in failing ventricles.

Human intelligence, as measured by intelligence quotient (IQ) tests, demonstrates one of the highest heritabilities among human quantitative traits. Nevertheless, studies to identify quantitative trait loci responsible for intelligence face challenges because of the small effect sizes of individual genes. Phenotypically discordant monozygotic (MZ) twins provide a feasible way to minimize the effects of irrelevant genetic and environmental factors, and should yield more interpretable results by finding epigenetic or gene expression differences between twins. Here we conducted array-based genome-wide DNA methylation and gene expression analyses using 17 pairs of healthy MZ twins discordant intelligently. ARHGAP18, related to Rho GTPase, was identified in pair-wise methylation status analysis and validated via direct bisulfite sequencing and quantitative RT-PCR. To perform expression profile analysis, gene set enrichment analysis (GSEA) between the groups of twins with higher IQ and their co-twins revealed up-regulated expression of several ribosome-related genes and DNA replication-related genes in the group with higher IQ. To focus more on individual pairs, we conducted pair-wise GSEA and leading edge analysis, which indicated up-regulated expression of several ion channel-related genes in twins with lower IQ. Our findings implied that these groups of genes may be related to IQ and should shed light on the mechanism underlying human intelligence.

Simple sequence repeat (SSR) markers were developed from expressed sequence tags (ESTs) for Mazus miquelii (Mazaceae), one of the most widespread species of the genus found in mainland China to Japan and North America, with the goal of elucidating the hidden genetic diversity and pollination ecology of the species. Of the initial 48 EST-SSR markers designed based on transcriptome data, 36 loci were successfully amplified, 16 of which were polymorphic. Polymorphisms for these markers were tested on 72 individuals from three populations in Japan. Two to eleven alleles per locus were detected, and the levels of observed and expected heterozygosity ranged from 0.181 to 0.708 and 0.154 to 0.715, respectively. Most loci were amplified successfully in five related Japanese and Taiwanese species. These markers will empower ecological and evolutionary studies in the creeping mazus and facilitate the disentanglement of phylogenetic relationships with related species. [ABSTRACT FROM AUTHOR]

In a revision of Berberis Sect. Wallichianae in Taiwan and Luzon, the Philippines, two of the authors recognized 11 species from Taiwan, including three new species. This article recognizes a further new species, Berberis morii, and places it in the same clade with other species from Taiwan. Rather than reproduce all the observations that were made there, we simply note that Taiwan is an important center of endemism of B. Sect. Wallichianae. In comparing the floral structure and overall morphology of B. morii with similar taxa from Taiwan, China and India, a series morphological differences, both qualitatively and quantitatively, were noted. Phylogenetic analysis was also used to evaluate the endemicity of B. morii. [ABSTRACT FROM AUTHOR]

As has long been known Berberis Sect. Wallichianae in Taiwan evidence a high species diversity all of which are endemic to the island. Though cytological data has been used to understand adaptive speciation for certain Berberis species elsewhere, little is still known about the chromosome numbers of Taiwanese Berberis. In this study, the chromosomes of eleven Taiwanese Berberis Sect. Wallichianae were counted for the first time and were all determined to be diploids (2n = 28). This result not only reconfirms previous studies elsewhere which have concluded that polyploidization may not be a dominant evolutionary process in Berberis but also suggests that geographic isolation or other extrinsic factors may play a more important role on the rapid speciation of Berberis in Taiwan. [ABSTRACT FROM AUTHOR]

Whether Mahonia should be recognized as a distinct genus or subsumed under Berberis has long been debated since its publication in 1818. Although recent molecular phylogenetic studies showed the paraphyly of Mahonia and some advocated a broadly defined Berberis to include Mahonia, the acceptance of Berberis s.l. is far from universal. Due to insufficient sampling and analytical issues of outgroup rooting, taxon misidentification, and the inclusion of a problematic GenBank DNA sequence, we argue that the phylogenetic status of Mahonia and consequently the circumscription of Berberis s.l. remains problematic. In particular, Berberis claireae and Mahonia sect. Horridae, taxa both inhabiting xeric habitats and characterized by a transitional morphology between Berberis s.str. and typical Mahonia (core Mahonia), have not been adequately sampled and well-positioned phylogenetically. With the inclusion of these key species and an expanded sampling of core Mahonia, we re-examine the phylogenetic relationships of Berberis s.l. using the internal transcribed spacer (ITS) of nrDNA, and three coding regions (accD, ndhF, rbcL) and one non-coding region (psbA-trnH) of the chloroplast genome. Our analyses reveal four clades within Berberis s.l., corresponding to Berberis s.str., B. claireae, core Mahonia, and Mahonia sect. Horridae, with the latter three (all compoundleaved) forming a paraphyletic grade sister to simple-leaved Berberis. Because of morphological and ecological distinctness of these four clades and their deep stem divergences equivalent to other genera of Berberidaceae, we propose a new classification of Berberis s.l. by applying a strict definition of Berberis (≡ Berberis s.str.), reinstating Mahonia (≡ core Mahonia), and proposing the two new genera Alloberberis nom. & stat. nov. (≡ Mahonia sect. Horridae) and Moranothamnus gen. nov. (≡ B. claireae). This revised classification is consistent with the traditional perception of Berberis and results in a monophyletic Mahonia, maintaining the stable usage of these two household names in both academic and non-academic commun [ABSTRACT FROM AUTHOR]

Brugada syndrome (BrS) is one of the ion channelopathies associated with sudden cardiac death (SCD). The most common BrS-associated gene (SCN5A) only accounts for approximately 20-25% of BrS patients. This study aims to identify novel mutations across human ion channels in non-familial BrS patients without SCN5A variants through disease-targeted sequencing. We performed disease-targeted multi-gene sequencing across 133 human ion channel genes and 12 reported BrS-associated genes in 15 unrelated, non-familial BrS patients withoutSCN5A variants. Candidate variants were validated by mass spectrometry and Sanger sequencing. Five de novo mutations were identified in four genes (SCNN1A, KCNJ16, KCNB2, and KCNT1) in three BrS patients (20%). Two of the three patients presented SCD and one had syncope. Interestingly, the two patients presented with SCD had compound mutations (SCNN1A:Arg350Gln and KCNB2:Glu522Lys; SCNN1A:Arg597* and KCNJ16:Ser261Gly). Importantly, two SCNN1A mutations were identified from different families. The KCNT1:Arg1106Gln mutation was identified in a patient with syncope. Bioinformatics algorithms predicted severe functional interruptions in these four mutation loci, suggesting their pivotal roles in BrS. This study identified four novel BrS-associated genes and indicated the effectiveness of this disease-targeted sequencing across ion channel genes for non-familial BrS patients without SCN5A variants. [ABSTRACT FROM AUTHOR]

Background Little evidence is available regarding the impact of genetic polymorphisms on the risk of stroke in patients with atrial fibrillation (AF). Angiotensin II plays a pathophysiologic role in prothrombotic atrial endocardial remodeling. Objective The purpose of this study was to investigate the effect of polymorphisms of renin-angiotensin system genes on the incidence of stroke in a prospective cohort of patients with AF. Methods A total of 712 AF patients were longitudinally followed-up for 10.3 ± 2.7 years. Eight polymorphisms of renin-angiotensin system genes were genotyped. Results Patients carrying the G-6 allele in the promoter of the angiotensinogen gene, which was associated with higher promoter activity, were more likely to develop stroke than were noncarriers (hazard ratio 2.54, 95% confidence interval [1.26-5.12], P = .009 after adjustment for CHADS2 score). G-6A polymorphism provides information additional to CHADS2 on stroke risk prediction (C-statistic 0.672 vs 0.724, P = .039). In haplotype analysis, angiotensinogen gene promoter haplotypes containing -217G/-6G, which was associated with the highest promoter activity, were associated with an increased risk of stroke (P = .004). G-217/G-6 haplotype carriers were even more likely to develop stroke than were noncarriers (hazard ratio 2.78, 95% confidence interval 1.37-5.64, P = .003 after multivariable adjustment). In pharmacogenetic analysis, the increased risk of stroke in subjects carrying G-6 was eliminated by concomitant treatment with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (P = .012 for interaction). Conclusion In addition to the CHADS2 score, angiotensinogen gene polymorphisms may be considered an additional genetic predictor of stroke in patients with AF. Genotyping of the angiotensinogen gene is helpful to determine which AF patients may benefit from treatment with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. [ABSTRACT FROM AUTHOR]

Brugada syndrome (BrS) is an inheritable sudden cardiac death disease mainly caused bySCN5A mutations. Traditional approaches can be costly and time-consuming if all candidate variants need to be validated throughin vitro studies. Therefore, we developed a new approach by combining multiple in silico analyses to predict functional and structural changes of candidate SCN5A variants in BrS before conducting in vitro studies. Five SCN5A non-synonymous variants (1651G>A, 1776C>G, 1673A>G, 3269C>T and 3578G>A) were identified in 14 BrS patients using direct DNA sequencing. Several bioinformatics algorithms were applied and predicted that 1651G>A (A551T) and 1776C>G (N592K) were high-risk SCN5A variants (odds ratio 59.59 and 23.93). The results were validated by Mass spectrometry and in vitro electrophysiological assays. We concluded that integrating sequence-based information and secondary protein structures elements may help select highly potential variants in BrS before conducting time-consuming electrophysiological studies and two novel SCN5A mutations were validated. [ABSTRACT FROM AUTHOR]

With atomic-layer-deposition grown zinc oxide as the electron selective layer, we developed plastic substrate compatible processing for organic photovoltaic devices and demonstrated flexible inverted organic solar cells on poly(ethylene naphthalate) with a power conversion efficiency of 4.18%. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish a national database of mutations in the fibrillin-1 ( FBN1) gene that cause Marfan syndrome (MFS) in the Taiwanese population. In this study, we screened 294 patients from 157 families for the presence of FBN1 mutations using polymerase chain reaction/ denaturing high performance liquid chromatography (PCR/DHPLC). We identified 56 mutations in 62 of the 157 (40%) families including 49 single-base substitutions (36 missense mutations, seven nonsense mutations, and six splicing sites), one small insertion, four small deletions, one small indel (insertion and deletion), and one exonic deletion (Exon 36). When family history was taken into consideration, the mutation detection rate rose to 91% (29 of 32). We further investigated the phenotypic data and found that one third (47 of 157) of the families fit the Ghent criteria for MFS. Based on that data, the mutation rate was 98% (46/47). That finding implies that family history and the Ghent criteria play a more important role than clinical manifestations in establishing a clinical diagnosis of Marfan syndrome. Among the 56 mutations found in this study, 40 (71%) have not been registered in the Human Gene Mutation Database (HGMD) or in the Universal Mutation Database (UMD). This is the first study of the mutation spectrum of MFS in a cohort of patients in Taiwan. The database is expected to considerably improve genetic counseling for and medical care of MFS families. [ABSTRACT FROM AUTHOR]

Solution cast and spin coating techniques were performed to deposit ferroelectric films of PVDF-PZT on Al3+-ZnO/polyethylene terephthalate(PET) flexible substrates. The composites with 10wt% PZT in PVDF exhibited higher dielectric permittivity and showed better ferroelectric property, might be due to internal field generated by the nano PZT particles, which favours the orientation of PVDF molecules. Higher remanent polarization and low leakage current were successfully demonstrated by coating PVDF layer on PVDF-PZT composite film. The surface of the obtained PVDF films were smooth with less porosity above PVDF-PZT composite film, enabling a significant decrease in the leakage current of composite thin films. [ABSTRACT FROM AUTHOR]

Low temperature processing of sol-gel spin coated ferroelectric Pb(Zr0.52Ti0.48)TiO3 (PZT) thin film and sputtered (La0.7Sr0.3)MnO3 (LSMO) buffer layer on Cr/SiO2/Si and SUS430 substrates using a continuous wave CO2 laser annealing technique was studied in the present work. The laser annealed PZT films coated on LSMO/Cr/SiO2/Si substrates shows an enhancement in the remanent polarization from 6.22 to 11.94 μC/cm2 as the PZT irradiated with a laser fluence of 267 to 334 W/cm2. The Cr electrodes were oxidized easily which deteriorate the electrical properties of specimens, even upon using CO2 laser annealing. On the other hand, the LSMO films (0.2 μm) sputtered on SUS430 substrate and spin coated PZT thin films (0.2 μm) were laser annealed sequentially, showed remanent polarization from 18.07 to 24.01 μC/cm2. CO2 laser annealing not only improves ferroelectric properties and electric leakage currents of PZT films, but also diminishes the inter-diffusion of elements in electrode and ferroelectrics. Moreover, laser annealing reduces oxidation of SUS430 and enhances the electrical performance of materials. [ABSTRACT FROM AUTHOR]

Pellets consisting of highly shape-selective HZSM-5 crystals prepared by chemical liquid deposition using tetraethyl orthosilicate (TEOS) as the silicon precursor were observed to be an effective catalyst for the alkylation of toluene with propylene in supercritical carbon dioxide. The p-cymene selectivity at a temperature of 523 K, a pressure of 11.72 MPa, a weight hourly space velocity of 4.56 (g of toluene)/(g of catalyst)/h, and a molar ratio of toluene to propylene of 7.7 was as high as 98%, indicating a pronounced shape-screening effect. The experimental results also indicated that propylene cracking could be significantly reduced compared to that under atmospheric pressure operation, indicating that supercritical CO2was an effective carrier for alkylation. When binder alumina was used in the preparation of pellets, chemical liquid deposition with a proper amount of TEOS could be applied right after the compression and calcination of the prepared shape-selective HZSM-5 crystals. With a proper ratio of TEOS to pellet, p-cymene yield and selectivity could be sufficiently close to those using the compressed pellets not containing alumina. [ABSTRACT FROM AUTHOR]

Diabetic subjects have been found to have low-grade inflammation, which has been thought to result in diabetic complications. Vascular adhesion protein-1 (VAP-1) is an adhesion molecule participating in inflammation and is elevated in subjects with diabetic complications, such as stroke, retinopathy, and nephropathy. We examined if serum VAP-1 is elevated in hyperglycemic stares. From 2005 to 2006, 386 subjects, including 225 female and 161 male, in Yun-Lin County, Taiwan, with fasting plasma glucose (FPG) < 126mg/dl during screening and did not take medication for diabetes were included. Anthropometric and biochemical profiles were measured. Serum VAP-1 levels were checked by immunofluorometrical method. During oral glucose tolerance test, serum VAP-1 levels were significantly elevated 2 hours after glucose challenge (540±138 vs. 561±119 ng/ml, p=0.0019). Those who had FPG ≥ 126 mg/dl had significantly higher fasting VAP- 1 levels (628±189 ng/ml) than those with impaired fasting glucose (531 ±165 ng/ml) or with normal fasting glucose (540±128 ng/ml, p=0.021 by ANOVA). Fasting VAP-1 levels were elevated in those who had 2-hour post-challenge plasma glucose ≥ 200 mg/dl (617±149 ng/ml) than that in impaired glucose tolerance (533±154 ng/ml) or normal glucose tolerance (531±128 ng/ml, p=0.015 by ANOVA). The average values of fasting and post-challenge VAP-1 were significantly associated to A1c, after adjusting for age and gender (regression coefficient, 35.2, p<0.001). In conclusion, serum VAP-1 levels were elevated in acute and chronic hyperglycemia. Serum VAP-1 may be a novel marker for low-grade inflammation in diabetic subjects. [ABSTRACT FROM AUTHOR]