Epidermal growth factor receptor signaling protects epithelia from morphogenetic instability and tissue damage in Drosophila.

Dying cells in the epithelia communicate with neighboring cells to initiate coordinated cell removal to maintain epithelial integrity. Naturally occurring apoptotic cells are mostly extruded basally and engulfed by macrophages. Here, we have investigated the role of Epidermal growth factor (EGF) receptor (EGFR) signaling in the maintenance of epithelial homeostasis. In Drosophila embryos, epithelial tissues undergoing groove formation preferentially enhanced extracellular signal-regulated kinase (ERK) signaling. In EGFR mutant embryos at stage 11, sporadic apical cell extrusion in the head initiates a cascade of apical extrusions of apoptotic and non-apoptotic cells that sweeps the entire ventral body wall. Here, we show that this process is apoptosis dependent, and clustered apoptosis, groove formation, and wounding sensitize EGFR mutant epithelia to initiate massive tissue disintegration. We further show that tissue detachment from the vitelline membrane, which frequently occurs during morphogenetic processes, is a key trigger for the EGFR mutant phenotype. These findings indicate that, in addition to cell survival, EGFR plays a role in maintaining epithelial integrity, which is essential for protecting tissues from transient instability caused by morphogenetic movement and damage.

Zinc-finger (ZiF) fold secreted effectors form a functionally diverse family across lineages of the blast fungus Magnaporthe oryzae.

Filamentous plant pathogens deliver effector proteins into host cells to suppress host defence responses and manipulate metabolic processes to support colonization. Understanding the evolution and molecular function of these effectors provides knowledge about pathogenesis and can suggest novel strategies to reduce damage caused by pathogens. However, effector proteins are highly variable, share weak sequence similarity and, although they can be grouped according to their structure, only a few structurally conserved effector families have been functionally characterized to date. Here, we demonstrate that Zinc-finger fold (ZiF) secreted proteins form a functionally diverse effector family in the blast fungus Magnaporthe oryzae. This family relies on the Zinc-finger motif for protein stability and is ubiquitously present in blast fungus lineages infecting 13 different host species, forming different effector tribes. Homologs of the canonical ZiF effector, AVR-Pii, from rice infecting isolates are present in multiple M. oryzae lineages. Wheat infecting strains of the fungus also possess an AVR-Pii like allele that binds host Exo70 proteins and activates the immune receptor Pii. Furthermore, ZiF tribes may vary in the proteins they bind to, indicating functional diversification and an intricate effector/host interactome. Altogether, we uncovered a new effector family with a common protein fold that has functionally diversified in lineages of M. oryzae. This work expands our understanding of the diversity of M. oryzae effectors, the molecular basis of plant pathogenesis and may ultimately facilitate the development of new sources for pathogen resistance.

Vein of Marshall chemical ablation decreases atrial fibrillation drivers detected by CARTOFINDER.

INTRODUCTION: This study sought to elucidate the impact of vein of Marshall (VOM) chemical ablation on atrial fibrillation (AF) drivers by investigating the changes in CARTOFINDER mappings before and after VOM chemical ablation in patients with persistent AF. METHODS: This study included 23 consecutive patients undergoing catheter ablation for long-persistent AF (>18 months). VOM chemical ablation was performed following pulmonary vein isolation. CARTOFINDER and AF cycle length (AFCL) maps were created in the left atrium (LA) before and after VOM chemical ablation. The LA was divided into 8 segments, and the number of focal activation points with 6 or more repetitions was counted in each segment. RESULTS: The number of focal activation points was largest in the LA appendage (LAA). After VOM chemical ablation, the number of focal activation points in the LA decreased significantly (37 [interquartile range, IQR: 19-55] vs. 15 [IQR: 7-21], p < .001), and median AFCL was significantly prolonged (159 [147-168] vs. 164 [150-173] ms, p < .001). In the assessment of each segment, significant decreases in focal activation points were observed in the inferior, lateral, and anterior segments and LAA. Among the focal activation points disappearing after chemical ablation, the number in the non-ethanol-affected area was significantly larger than that in the affected area (13 [8-25] vs. 4 [1-10], p < .001). CONCLUSIONS: VOM chemical ablation decreases AF drivers detected by CARTOFINDER. Mechanisms other than direct myocardial damage are considered to contribute the attenuation of AF drivers.

Identification of the causal mutation in early heading mutant of bread wheat (Triticum aestivum L.) using MutMap approach.

In bread wheat (Triticum aestivum L.), fine-tuning the heading time is essential to maximize grain yield. Photoperiod-1 (Ppd-1) and VERNALIZATION 1 (Vrn-1) are major genes affecting photoperiod sensitivity and vernalization requirements, respectively. These genes have predominantly governed heading timing. However, Ppd-1 and Vrn-1 significantly impact heading dates, necessitating another gene that can slightly modify heading dates for fine-tuning. In this study, we developed an early heading mutant from the ethyl methanesulfonate-mutagenized population of the Japanese winter wheat cultivar "Kitahonami." MutMap analysis identified a nonsense mutation in the clock component gene Wheat PHYTOCLOCK 1/LUX ARRHYTHMO (WPCL-D1) as the probable SNP responsible for the early heading mutant on chromosome 3D. Segregation analysis using F2 and F3 populations confirmed that plants carrying the wpcl-D1 allele headed significantly earlier than those with the functional WPCL-D1. The early heading mutant exhibited increased expression levels of Ppd-1 and circadian clock genes, such as WPCL1 and LATE ELONGATED HYPOCOTYL (LHY). Notably, the transcript accumulation levels of Ppd-A1 and Ppd-D1 were influenced by the copy number of the functional WPCL1 gene. These results suggest that a loss-of-function mutation in WPCL-D1 is the causal mutation for the early heading phenotype. Adjusting the functional copy number of WPCL1 will be beneficial in fine-tuning of heading dates. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01478-5.

Atypical TDP-43 proteinopathy clinically presenting with progressive nonfluent aphasia: A case report.

Progressive nonfluent aphasia (PNFA) is a form of frontotemporal lobar degeneration (FTLD) caused by tau and transactive response DNA-binding protein of 43 kDa (TDP-43) accumulation. Here we report the autopsy findings of a 64-year-old right-handed man with an atypical TDP-43 proteinopathy who presented with difficulties with speech, verbal paraphasia, and dysphagia that progressed over the 36 months prior to his death. He did not show pyramidal tract signs until his death. At autopsy, macroscopic brain examination revealed atrophy of the left dominant precentral, superior, and middle frontal gyri and discoloration of the putamen. Spongiform change and neuronal loss were severe on the cortical surfaces of the precentral, superior frontal, and middle frontal gyri and the temporal tip. Immunostaining with anti-phosphorylated TDP-43 revealed neuronal cytoplasmic inclusions and long and short dystrophic neurites in the frontal cortex, predominantly in layers II, V, and VI of the temporal tip, amygdala, and transentorhinal cortex. Immunoblot analysis of the sarkosyl-insoluble fractions showed hyperphosphorylated TDP-43 bands at 45 kDa and phosphorylated C-terminal fragments at approximately 25 kDa. The pathological distribution and immunoblot band pattern differ from the major TDP-43 subtype and therefore may represent a new FTLD-TDP phenotype.

Corticobasal degeneration with visual hallucination as an initial symptom: A case report.

Although the initial symptoms of corticobasal degeneration (CBD) are varied, psychiatric symptoms are uncommon. Here, we report the autopsy findings of a patient with early CBD who presented with hallucinations. A 68-year-old man developed memory loss and visions of bears and insects. Because of slow vertical eye movement, postural instability, and levodopa-unresponsive parkinsonism, the patient initially was clinically diagnosed with progressive supranuclear palsy. He died of a urinary tract infection 11 months after the onset of the disease. Histopathological examination revealed neuronal loss and gliosis, which were severe in the substantia nigra and moderate in the globus pallidus and subthalamic nucleus. Astrocytic plaques were scattered throughout the amygdala and premotor cortex. The superficial cortical layers lacked ballooned neurons and spongiosis, and tau deposition was greater in glia than in neurons. The amygdala contained a moderate number of argyrophilic grains and pretangles. Western blot analysis showed a 37-kDa band among the low-molecular-weight tau fragments. Because the CBD pathology was mild, we attributed the patient's visual hallucinations to the marked argyrophilic grain pathology. CBD can occur with psychiatric symptoms, including visual hallucinations, and argyrophilic grain pathology may be associated with psychiatric symptoms.

Unidirectional conduction characterizing epicardial connections in patients with atrial tachyarrhythmias.

INTRODUCTION: Electrophysiological characteristics of epicardial connections (ECs) in atria and pulmonary veins (PVs) are unclear despite their important contributions to atrial fibrillation (AF). Unidirectional conduction associated with source-sink mismatch can occur in ECs due to their fine fibers with abrupt changes in orientation. We detailed the prevalence and electrophysiological characteristics of unidirectional conduction in the atria and investigated its association with the clinical manifestation of AF. METHODS: This study retrospectively reviewed electrophysiological studies and radiofrequency catheter ablation in 261 consecutive patients with AF. RESULTS: Unidirectional conduction was observed during ablation encircling the PVs in eight (3.1%) patients, and all occurred in the suspected (N = 4) or definitively (N = 4) recognized ECs. These ECs included three intercaval bundles, four septopulmonary bundles, and one Marshall bundle, and were first manifested in a second procedure in 6 (75%) patients. The unidirectional property was from PV to atrium (exit conduction) in all intercaval bundles and three septopulmonary bundles, and from atrium to PV (entrance conduction) in the remaining two bundles. Intercaval bundles acted as a limb of bi-atrial macro-reentrant tachycardia (50%, three of the six including previous cases). Ablation of the exit outside the PVs, including the right atrium, eliminated ECs in three (38%) patients. All patients remain free from arrhythmia recurrence after a mean 13-month follow-up. CONCLUSION: A unidirectional conduction property was closely associated with the EC, as estimated by histological findings. Recognition of this fact by electrophysiologists may help to clarify mechanisms for AF and atrial tachycardia and guide the creation of efficient and safe ablation lesion sets.

Impact of Interatrial Epicardial Connections on the Dominant Frequency of Atrial Fibrillation.

BACKGROUND: An epicardial connection (EC) between the right-sided pulmonary venous (RtPV) carina and right atrium (RA) may preclude PV isolation, but its electrophysiological role during atrial fibrillation (AF) remains unknown.Methods and Results: This prospective observational study included 98 consecutive patients undergoing catheter ablation for AF, subdivided into the EC group (n=17) and non-EC group (n=80) based on observation of RA posterior wall breakthrough during RtPV pacing. Mean left atrial (LA) dominant frequency (mean DFLA) was defined as the averaged DFs at the right and left PVs and LA appendage. The regional DF was higher in the EC group vs. the non-EC group except at the left PV antrum. The DF at the RA appendage (RAA) and mean DFLAwere equivocal (6.5±0.7 vs. 6.6±0.7 Hz) in the EC group, but the mean DFLAwas significantly higher than that at the RAA (5.8±0.6 vs. 6.1±0.5 Hz, P=0.001) in the non-EC group, suggesting an LA-to-RA DF gradient. A significant correlation of DF between the RtPV antrum and RAA was observed in the EC group (P<0.001, r=0.84) but not in the non-EC group. CONCLUSIONS: An electrophysiological link via interatrial ECs might attenuate the hierarchical nature of activation frequencies of AF, leading to advanced electrical remodeling of the atria.

Genome sequencing-based coverage analyses facilitate high-resolution detection of deletions linked to phenotypes of gamma-irradiated wheat mutants.

BACKGROUND: Gamma-irradiated mutants of Triticum aestivum L., hexaploid wheat, provide novel and agriculturally important traits and are used as breeding materials. However, the identification of causative genomic regions of mutant phenotypes is challenging because of the large and complicated genome of hexaploid wheat. Recently, the combined use of high-quality reference genome sequences of common wheat and cost-effective resequencing technologies has made it possible to evaluate genome-wide polymorphisms, even in complex genomes. RESULTS: To investigate whether the genome sequencing approach can effectively detect structural variations, such as deletions, frequently caused by gamma irradiation, we selected a grain-hardness mutant from the gamma-irradiated population of Japanese elite wheat cultivar "Kitahonami." The Hardness (Ha) locus, including the puroindoline protein-encoding genes Pina-D1 and Pinb-D1 on the short arm of chromosome 5D, primarily regulates the grain hardness variation in common wheat. We performed short-read genome sequencing of wild-type and grain-hardness mutant plants, and subsequently aligned their short reads to the reference genome of the wheat cultivar "Chinese Spring." Genome-wide comparisons of depth-of-coverage between wild-type and mutant strains detected ~ 130 Mbp deletion on the short arm of chromosome 5D in the mutant genome. Molecular markers for this deletion were applied to the progeny populations generated by a cross between the wild-type and the mutant. A large deletion in the region including the Ha locus was associated with the mutant phenotype, indicating that the genome sequencing is a powerful and efficient approach for detecting a deletion marker of a gamma-irradiated mutant phenotype. In addition, we investigated a pre-harvest sprouting tolerance mutant and identified a 67.8 Mbp deletion on chromosome 3B where Viviparous-B1 and GRAS family transcription factors are located. Co-dominant markers designed to detect the deletion-polymorphism confirmed the association with low germination rate, leading to pre-harvest sprouting tolerance. CONCLUSIONS: Short read-based genome sequencing of gamma-irradiated mutants facilitates the identification of large deletions linked to mutant phenotypes when combined with segregation analyses in progeny populations. This method allows effective application of mutants with agriculturally important traits in breeding using marker-assisted selection.

Apophyllite waveplates.

We investigate the polarization characteristics of apophyllite crystals in an attempt to evaluate their potential use for achromatic waveplates. Among the 50 plates that we extracted and polished from natural apophyllite crystals, a few show the sought-for characteristic of birefringence that increases linearly with the wavelength. However, we also find that the crystals among our samples exhibit a sectored structure in their polarization properties, as well as an undesirable degree of spatial nonuniformity.

Repeated Cardioembolic Stroke after COVID-19 mRNA Vaccination: A Case Report.

OBJECTIVE: There have been no reports suggesting a relationship between the COVID-19 mRNA vaccines that encodes the spike glycoprotein of SARS-CoV-2 and cerebrovascular disease. A case of repeated cardioembolic stroke after vaccination with the BNT162b2 (Pfizer) COVID-19 mRNA vaccine is presented. METHODS: Imaging and laboratory findings, treatment decisions, and the outcome of this case are presented. RESULTS: An 83-year-old Japanese woman developed right hemiplegia and motor aphasia three days after receiving her first dose of the BNT162b2 (Pfizer) COVID-19 mRNA vaccine. She had been taking rivaroxaban for persistent atrial fibrillation for 10 years, but had no symptomatic ischemic strokes. On magnetic resonance imaging (MRI) the left middle cerebral artery (MCA) was occluded. Intravenous recombinant tissue-plasminogen activator (rt-PA) therapy and mechanical thrombectomy were performed, and she recovered almost fully. However, three days after the second dose, she developed left hemiplegia and left hemispatial neglect. MRI showed occlusion of the right MCA. Only mechanical thrombectomy was performed again, but it could not be resumed due to the hard thrombus. DISCUSSION: In this case, it is difficult to exclude a causal relationship between the COVID-19 mRNA vaccine and ischemic stroke. This association needs to be carefully monitored.

RNA-Seq-based DNA marker analysis of the genetics and molecular evolution of Triticeae species.

The release of high-quality chromosome-level genome sequences of members of the Triticeae tribe has greatly facilitated genetic and genomic analyses of important crops such as wheat (Triticum aestivum) and barley (Hordeum vulgare). Due to the large diploid genome size of Triticeae plants (ca. 5 Gbp), transcript analysis is an important method for identifying genetic and genomic differences among Triticeae species. In this review, we summarize our results of RNA-Seq analyses of diploid wheat accessions belonging to the genera Aegilops and Triticum. We also describe studies of the molecular relationships among these accessions and provide insight into the evolution of common hexaploid wheat. DNA markers based on polymorphisms within species can be used to map loci of interest. Even though the genome sequence of diploid Aegilops tauschii, the D-genome donor of common wheat, has been released, the diploid barley genome continues to provide key information about the physical structures of diploid wheat genomes. We describe how a series of RNA-Seq analyses of wheat relatives has helped uncover the structural and evolutionary features of genomic and genetic systems in wild and cultivated Triticeae species.

A simple pacing maneuver to unmask an epicardial connection involving the right-sided pulmonary veins.

INTRODUCTION: An epicardial connection (EC) between the right-sided pulmonary venous (PV) carina and right atrium (RA) is one of the mechanisms for which carinal ablation is required for right-sided PV isolation. The purpose of the study was to devise a simple pacing maneuver to differentiate an EC from a residual conduction gap on the antral ablation line during radiofrequency catheter ablation. METHODS AND RESULTS: This study included 133 consecutive patients. After one round of ablation, electrograms at the posterior antrum outside the ablation line were recorded during sinus rhythm (SR) and coronary sinus (CS) pacing, and intervals between the antral and PV potentials were measured in each rhythm. The ΔintervalSR-CS was calculated as the difference between the interval during SR and that during CS pacing. Presence of an EC was confirmed by observation of a RA posterior wall breakthrough during right-sided PV pacing, which was then targeted for ablation. Patients with nonachievement of first-pass isolation (N = 35) and with PV reconnection during the procedure (N = 9) were classified into the EC-group (N = 20) and gap-group (N=24), respectively. The prevalence of carina breakthrough during SR was higher in the EC-group than the gap-group (18 [95%] vs. 1 [4%] patients, p < .0001). The ΔintervalSR-CS was larger in the EC-group versus gap-group (71 [interquartile range, 57-97] vs. 6 [2-9] ms, p < .0001). In all patients with an EC, RA ablation resulted in delay (32 [20-40] ms) (N = 15) or elimination of PV potentials (N = 5). CONCLUSION: An EC can be efficiently discriminated from a conduction gap by a simple pacing maneuver.

An autopsy case of PARK2 due to a homozygous exon 2 deletion of parkin and associated with α-synucleinopathy.

Lewy bodies (LBs) are usually detected in patients with idiopathic Parkinson's disease (PD), but there have been few reports of LBs in a familial form of early-onset PD associated with several mutations in parkin, a gene that encodes a ubiquitin E3 ligase involved in mitochondrial homeostasis, being also known as PARK2. Here, we report a case of PD with a PARK2 mutation characterized by a homozygous deletion of exon 2 and incidental LB pathology. A 60-year-old man developed tremor in the upper limbs. Although levodopa was initially effective, his symptoms slowly progressed. His cardiac uptake of 123 I-metaiodobenzylguanidine, as assessed by myocardial scintigraphy, decreased from an early stage after the onset. At the age of 81 years, he developed Legionella pneumonia and died of respiratory failure. Histopathological examination revealed a moderate loss of pigmented neurons, as well as gliosis in the substantia nigra and the locus coeruleus. Little LB-related pathology was found in the locus coeruleus, dorsal nucleus of vagal nerve, and basal nucleus of Meynert. The cardiac sympathetic nerve in the epicardium showed a reduction in the numbers of fibers immunoreactive for tyrosine hydroxylase and phosphorylated neurofilament protein. Genetic analysis of frozen brain materials revealed a homozygous deletion of exon 2 of parkin. To our knowledge, this is the first autopsy case with a homozygous deletion of exon 2 of parkin. The number of LBs was small, the age of disease onset was later than that in typical PARK2-associated PD patients, and cardiac sympathetic denervation was also present. Thus, we considered the LBs in our case as incidental and preclinical α-synucleinopathy.

Nitroxyl Radical/Copper-Catalyzed Electrooxidation of Alcohols and Amines at Low Potentials.

Nitroxyl radicals, such as 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO), can catalyze the electrochemical oxidation of alcohols and amines. Because the oxidation current obtained in this process depends on the concentration of alcohols and amines, this process can be applied to their sensing. However, the relatively high oxidation potentials required by nitroxyl radicals can induce interfering oxidation currents from various reductive substances in biological samples, which affects the accuracy of analyte measurements. In this study, we examined the electrooxidation of alcohols and amines at a low potential by applying cooperative oxidation catalysis using a nitroxyl radical and a copper salt. Nortropine N-oxyl (NNO), which showed higher catalytic activity than TEMPO was used as the nitroxyl radical. An increase in the oxidation current was observed at the low potential, and this increase depended on the alcohol concentration. In the case of the electrooxidation of amines, a positive correlation between oxidation current and amine concentration was observed at low amine concentrations. Therefore, low-potential cooperative catalysis can be applied to alcohol and amine electrooxidation for the development of accurate sensors suitable for clinical settings.

Predictors of Reperfusion and 90-day Functional Outcome After Mechanical Thrombectomy for Large Vessel Occlusion Strokes.

OBJECTIVES: Whether elderly patients with adverse comorbidities or strong vascular meandering benefit from mechanical thrombectomy to the same degree as patients who participated in the pivotal randomized controlled trials on this procedure (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, DAWN, and DEFUSE 3) remains unknown. We aimed to investigate the predictors of reperfusion and 90-day functional outcome using real-world clinical data, without excluding elderly patients with adverse comorbidities or patients in whom vascular access could not be achieved. MATERIALS AND METHODS: We retrospectively reviewed consecutive patients with acute ischemic stroke who underwent or in whom mechanical thrombectomy was attempted at Japanese Red Cross Matsue Hospital from April 2015 to June 2020. RESULTS: Altogether, 111 mechanical thrombectomies in 111 patients (average age 77.2 years) were attempted for acute ischemic stroke. Vascular access was not achieved in 8 (7.2%) cases. In the multivariable analysis, age ≥85 years (odd ratio [OR] 0.191, 95% confidence interval [CI] 0.057-0.641, p = 0.007) and presence of adverse comorbidities (OR 0.265, 95% CI 0.090-0.659, p = 0.016) were associated with failed reperfusion. The diffusion-weighted imaging (DWI)-ASPECT score ≥6 (OR 4.650, 95% CI 1.610-13.40, p = 0.005) was associated with good 90-day functional outcomes. Presence of adverse comorbidities was not a predictor, but it had a relatively strong correlation with poor functional outcome. CONCLUSIONS: Mechanical thrombectomy in elderly patients should be considered very carefully if they are aged ≥85 years, have low DWI-ASPECT score and have clear evidence of pre-existing adverse comorbidities.

Catheter Ablation of Refractory Ventricular Fibrillation Storm After Myocardial Infarction.

BACKGROUND: Ventricular fibrillation (VF) storm after myocardial infarction (MI) is a life-threatening condition that necessitates multiple defibrillations. Catheter ablation is a potentially effective treatment strategy for VF storm refractory to optimal medical treatment. However, its impact on patient survival has not been verified in a large population. METHODS: We conducted a multicenter, retrospective observational study involving consecutive patients who underwent catheter ablation of post-MI refractory VF storm without preceding monomorphic ventricular tachycardia. The target of ablation was the Purkinje-related ventricular extrasystoles triggering VF. The primary outcome was in-hospital and long-term mortalities. Univariate logistic regression and Cox proportional-hazards analysis were used to evaluate clinical characteristics associated with in-hospital and long-term mortalities, respectively. RESULTS: One hundred ten patients were enrolled (age, 65±11years; 92 men; left ventricular ejection fraction, 31±10%). VF storm occurred at the acute phase of MI (4.5±2.5 days after the onset of MI during the index hospitalization for MI) in 43 patients (39%), the subacute phase (>1 week) in 48 (44%), and the remote phase (>6 months) in 19 (17%). The focal triggers were found to originate from the scar border zone in 88 patients (80%). During in-hospital stay after ablation, VF storm subsided in 92 patients (84%). Overall, 30 (27%) in-hospital deaths occurred. The duration from the VF occurrence to the ablation procedure was associated with in-hospital mortality (odds ratio for each 1-day increase, 1.11 [95% CI, 1.03-1.20]; P=0.008). During follow-up after discharge from hospital, only 1 patient developed recurrent VF storm. However, 29 patients (36%) died, with a median survival time of 2.2 years (interquartile range, 1.2-5.5 years). Long-term mortality was associated with left ventricular ejection fraction <30% (hazard ratio, 2.54 [95% CI, 1.21-5.32]; P=0.014), New York Heart Association class ≥III (hazard ratio, 2.68 [95% CI, 1.16-6.19]; P=0.021), a history of atrial fibrillation (hazard ratio, 3.89 [95% CI, 1.42-10.67]; P=0.008), and chronic kidney disease (hazard ratio, 2.74 [95% CI, 1.15-6.49]; P=0.023). CONCLUSIONS: In patients with MI presenting with focally triggered VF storm, catheter ablation of culprit triggers is lifesaving and appears to be associated with short- and long-term freedom from recurrent VF storm. Mortality over the long-term follow-up is associated with the severity of underlying cardiovascular disease and comorbidities in this specific patient population.

Diploid genome differentiation conferred by RNA sequencing-based survey of genome-wide polymorphisms throughout homoeologous loci in Triticum and Aegilops.

BACKGROUND: Triticum and Aegilops diploid species have morphological and genetic diversity and are crucial genetic resources for wheat breeding. According to the chromosomal pairing-affinity of these species, their genome nomenclatures have been defined. However, evaluations of genome differentiation based on genome-wide nucleotide variations are still limited, especially in the three genomes of the genus Aegilops: Ae. caudata L. (CC genome), Ae. comosa Sibth. et Sm. (MM genome), and Ae. uniaristata Vis. (NN genome). To reveal the genome differentiation of these diploid species, we first performed RNA-seq-based polymorphic analyses for C, M, and N genomes, and then expanded the analysis to include the 12 diploid species of Triticum and Aegilops. RESULTS: Genetic divergence of the exon regions throughout the entire chromosomes in the M and N genomes was larger than that between A- and Am-genomes. Ae. caudata had the second highest genetic diversity following Ae. speltoides, the putative B genome donor of common wheat. In the phylogenetic trees derived from the nuclear and chloroplast genome-wide polymorphism data, the C, D, M, N, U, and S genome species were connected with short internal branches, suggesting that these diploid species emerged during a relatively short period in the evolutionary process. The highly consistent nuclear and chloroplast phylogenetic topologies indicated that nuclear and chloroplast genomes of the diploid Triticum and Aegilops species coevolved after their diversification into each genome, accounting for most of the genome differentiation among the diploid species. CONCLUSIONS: RNA-sequencing-based analyses successfully evaluated genome differentiation among the diploid Triticum and Aegilops species and supported the chromosome-pairing-based genome nomenclature system, except for the position of Ae. speltoides. Phylogenomic and epigenetic analyses of intergenic and centromeric regions could be essential for clarifying the mechanisms behind this inconsistency.

Oral caffeine intake amplifies the effect of isoproterenol in patients with frequent premature ventricular contractions.

AIMS: Infrequent appearance and failed induction of premature ventricular contractions (PVCs) at catheter ablation make their localization difficult and are associated with a poor procedural outcome. This study aimed to assess the effect of preprocedural oral caffeine intake on induction of PVCs during catheter ablation. METHODS AND RESULTS: Seventy patients (age: 54 ± 14 years, 37 men) undergoing catheter ablation for monofocal PVCs were randomized to receive oral caffeine (5 mg/kg) or placebo. Before ablation, PVC counts for 5 min were performed at baseline and during isoproterenol infusion and the isoproterenol washout period. PVC count fluctuation was defined as the difference between the highest and lowest 5-min count among the three-time periods. The 5-min PVC counts during baseline and isoproterenol infusion were equivalent between the groups. However, those during the isoproterenol washout period and PVC count fluctuation were significantly higher in the caffeine group than the control group (73.1 ± 73.2 vs. 38.9 ± 28.9 beats/5 min, P = 0.012 and 69.3 ± 61.3 vs. 37.7 ± 30.9 beats/5 min, P = 0.008, respectively). The procedure and ablation times were significantly shorter in the caffeine group than the control group (105.0 ± 23.4 vs. 136.9 ± 43.2 min, P < 0.01 and 219.1 ± 104.7 vs. 283.5 ± 136.0 sec, P < 0.01, respectively). CONCLUSION: Oral caffeine intake amplified the effect of isoproterenol infusion on PVC induction during catheter ablation. The combined use of oral caffeine intake and isoproterenol infusion can be an option to increase intraprocedural PVCs.

Difference in epicardial adipose tissue distribution between paroxysmal atrial fibrillation and coronary artery disease.

BACKGROUND: An increase in epicardial adipose tissue (EAT) volume is associated with the development of atrial fibrillation (AF) and coronary artery disease (CAD), but little is known about differences in its distribution. METHODS AND RESULTS: We included 50 patients with paroxysmal AF (PAF), 50 patients with CAD, and 50 control patients. Using multidetector computed tomography, EAT volumes surrounding the whole heart (total EAT), the atrium (atrial-EAT), and the ventricle (ventricular-EAT) were measured. EAT atrial/ventricular (A/V) ratio was calculated by dividing atrial- by ventricular-EAT volume. The total EAT volume indexes in the PAF and CAD groups were significantly larger than those in the control group. The atrial-EAT volume index in the PAF group was significantly larger than that in the CAD and control groups, whereas the ventricular-EAT volume index in the CAD group was significantly larger than that in the PAF and control groups. Thus, EAT A/V ratio was smaller in the CAD and control group than that in the PAF group (0.28 ± 0.12 vs. 0.38 ± 0.13 vs. 0.54 ± 0.33, P < .001). Univariate and multivariate linear regression analysis showed EAT A/V ratio to be independently associated with cardiovascular disease type (PAF vs. CAD; P < .001, ß = .463). CONCLUSIONS: Atrial- and ventricular-dominant distribution of EAT was observed in the PAF and CAD groups, respectively. Uneven distribution of EAT may imply the direct contribution of EAT-related inflammation to the pathogenesis of AF or CAD.