bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2869Role of PDE8 in cAMP dynamics in human atrial fibrillation
Authors: Grammatika Pavlidou N , Pecha S , Reichenspurner H , Christ T , Nikolaev V O , Molina C E 
Published: October 2019

Abstract

Background
Cardiac arrhythmias, such as atrial fibrillation (AF), are often related to remodeling of membrane receptors and alterations in cAMP-dependent regulation of Ca2+ handling mechanisms. For instance, decreased L-type calcium current (ICa,L) density but upregulated RyR2 are major hallmarks of AF. These inhomogeneous AF-associated changes of protein phosphorylation point to a local regulation of PKA activity within these intracellular compartments. Local cAMP compartmentation and the role of phosphodiesterase (PDEs) have ben extensively studied in ventricular myocytes from animals. However, only a few studies have evaluated the contribution of PDEs to the pathophysiology of AF and the reason for the persistent AF-associated hypophosphorylation of the L-type calcium channel (LTCC) is currently unknown. The aim of this study was to investigate whether a change in the expression level of PDE8 in human atrium may affects cAMP nearby LTCC promoting the reduction of the ICa,L observed in persistent AF.

Methods
Atrial myocytes were isolated from tissue of 47 patients in sinus rhythm (SR) and with AF. Cells were then transfect with an adenovirus (Epac1-camps or pm-Epac1-camps) in order to express the (cytosolic or membrane, respectively) FRET-based cAMP sensor and cultured during 48 hours. Föster-resonance energy transfer (FRET) was used to measure cAMP in 232 isolated human atrial myocytes. Ro-20-1724 (10 μM), Cilostamide (1 μM) and PF-04957325 (30 nM) and IBMX (100 μM) were used as PDE4, PDE3, PDE8 and non-selective phosphodiesterases (PDEs) inhibitor respectively.

Results
Effects of PDE4 and especially PDE3 inhibition on cytosolic [cAMP] are reduced in AF. Pharmacological PDE8 inhibition induces only a small increase in basal intracellular [cAMP] in AF but it showed a big synergic effect when PDE4 was inhibit at the same time. By contrast, PDE8 inhibition dramatically increased basal [cAMP] in the subsarcolemmal compartment in AF while PDE3 or PDE4 inhibition had a smaller effect that didn't change between SR and AF.

Conclusions
PDE8 controls basal cytosolic cAMP levels in human atrial myocytes from patients with persistent AF while PDE3 effects tends to be reduced in these patients. Furthermore, PDE8 is the main PDE in controlling cAMP levels at the membrane in persistent AF. Thus, our study may provide a clue for the reported reduction of the ICa,L in persistent AF.
P2883VT/VF treatment in a contemporary population of single chamber ICD recipients: ATP efficacVF
Authors: Angeletti A , Paolisso P , Statuto G , Massaro G , Lorenzetti S , Frisoni J , Martignani C , Ziacchi M , Giacopelli D , Grassini D , Diemberger I , Biffi M 
Published: October 2019

Abstract

Aim of the study
to investigate the efficacy of ATP in consecutive, unselected ICD recipients implanted in 2014–2015.

Methods
All patients had a VT zone as 350 ms and a VF zone as 280 ms programmed, with a detection duration >20 seconds and >8 seconds respectively for VT and VF. Anti-tachycardia pacing (ATP) was available before/during charging in the VF zone, while at least 3 attempts with ATP were programmed in the VT zone. ATP efficacy was assed at the first ventricular arrhythmia episode for each patient. Overall ATP efficacy was also calculated on the burden of treated episodes.

Results
A total of 165 patients (median age 63 [48–72] years, male 79%, primary prevention 80%, ischemic 53%) implanted with a single chamber ICD were followed for a median period of 847 [666–1030] days: 44 (27%) had VT/VF episodes. Among a total of 706 VT/VF episodes, 623 were treated with ATP and/or shock. 7 patients were treated with shock as first delivered therapy (efficacy 100%), whereas 33 were treated with ATP (efficacy 55% of treated patients, 71% of episodes). The median cycle of the treated arrhythmias was 309 [280–324] ms.
Efficacy at first attempt ALL Ischemic NICM Primary Secondary Per patient (first therapy occurrence)   Shock (7/7) 100% (7/7) 100% – (6/6) 100% (1/1) 100%   ATP (18/33) 55% (13/23) 57% (5/10) 50% (13/22) 59% (5/11) 45% Per episode   Shock (14/14) 100% (14/14) 100% – (6/6) 59% (8/8) 100%   ATP (432/609) 71% (245/362) 68% (187/247) 76% (127/201) 63% (305/408) 75%

Conclusion
ATP is quite effective is a contemporary cohort of single chamber ICD recipients in a fast arrhythmia range (average 190–220 bpm) with a long detection. This observation strengthen the value of ATP in ICD selection, and should be balancen when considering an S-ICD.
Profound reductions in first and total cardiovascular events with icosapent ethyl in the REDUCE-IT trial: why these results usher in a new era in dyslipidaemia therapeutics
Authors: Boden William E , Bhatt Deepak L , Toth Peter P , Ray Kausik K , Chapman M John , Lüscher Thomas F 
Published: October 2019

Abstract
The aims of this clinical review are to: (i) highlight the importance of elevated baseline triglycerides (TG) in the setting of well-controlled low-density lipoprotein cholesterol (LDL-C) on statins as a major contributor to residual atherosclerotic cardiovascular disease (ASCVD) risk, particularly among patients with type 2 diabetes mellitus, metabolic syndrome, and obesity whose distinctive lipid phenotype cannot be optimally treated with LDL-C reduction therapy alone; (ii) describe the findings and clinical implications of the landmark REDUCE-IT trial in which ethyl eicosapentaenoic acid significantly improved ASCVD outcomes. While many genetic studies have shown that elevated TG are an independent causal factor for ASCVD, prior placebo-controlled trials using niacin, fibrates, omega-3 fatty acids, and dietary supplement fish oil preparations have failed to demonstrate significant CV event reduction when added to statin therapy. In contrast, the REDUCE-IT trial in 8179 participants showed convincingly that the administration of 4 g daily of icosapent ethyl (an ethyl ester of eicosapentaenoic acid) in patients at high risk for ASCVD with increased levels of baseline TG [median value, 2.44 mmol/L (216.0 mg/dL)] but well-controlled LDL-C [median value, 1.94 mmol/L (75.0 mg/dL)] reduced significantly incident events across both the trial primary endpoint and multiple prespecified secondary endpoints, including cardiovascular death, as well as both subsequent and total primary endpoint and key secondary endpoint events. Icosapent ethyl unequivocally contributed to ASCVD event reduction over and above statin therapy. The REDUCE-IT trial results should alter our approach to managing a growing population of hypertriglyceridaemic patients whose lipid phenotype requires more intensive treatment beyond LDL-C lowering alone.
Non-invasive assessment of the arrhythmogenic substrate in Brugada syndrome using signal-averaged electrocardiogram: clinical implications from a prospective clinical trial
Authors: Ciconte Giuseppe , Santinelli Vincenzo , Vicedomini Gabriele , Borrelli Valeria , Monasky Michelle M , Micaglio Emanuele , Giannelli Luigi , Negro Gabriele , Giordano Federica , Mecarocci Valerio , Mazza Beniamino C , Locati Emanuela , Anastasia Luigi , Calovic Zarko , Pappone Carlo 
Published: October 2019

AbstractAimsBrugada syndrome (BrS) represents a major cause of sudden cardiac death in young individuals. The risk stratification to forecast future life-threatening events is still controversial. Non-invasive assessment of late potentials (LPs) has been proposed as a risk stratification tool. However, their nature in BrS is still undetermined. The purpose of this study is to assess the electrophysiological determinants of non-invasive LPs.Methods and ResultsTwo hundred and fifty consecutive patients with (Group 1, n = 96) and without (Group 2, n = 154) BrS-related symptoms were prospectively enrolled in the registry. Signal-averaged electrocardiogram (SAECG) was performed in all subjects before undergoing epicardial mapping. Group 1 patients exhibited larger arrhythmogenic substrates (AS; 5.8 ± 2.8 vs. 2.6 ± 2.1 cm2, P < 0.001) with more delayed potentials (220.4 ± 46.0 vs. 186.7 ± 42.3 ms, P < 0.001). Late potentials were present in 82/96 (85.4%) Group 1 and in 31/154 (20.1%) Group 2 individuals (P < 0.001). Patients exhibiting LPs had more frequently a spontaneous Type 1 pattern (30.1% vs. 10.9%, P < 0.001), SCN5A mutation (34.5% vs. 21.2%, P = 0.02), and exhibited a larger AS with longer potentials (5.8 ± 2.7 vs. 2.2 ± 1.7 cm2; 231.2 ± 37.3 vs. 213.8 ± 39.0 ms; P < 0.001, respectively). Arrhythmogenic substrate dimension was the strongest predictor of the presence of LPs (odds ratio 1.9; P < 0.001). An AS area of at least 3.5 cm2 identified patients with LPs (area under the curve 0.88, 95% confidence interval 0.843–0.931; P < 0.001) with a sensitivity of 86%, specificity 88%, positive predictive value 85%, and negative predictive value 89%.ConclusionThe results of this study support the role of the epicardial AS as an electrophysiological determinant of non-invasive LPs, which may serve as a tool in the non-invasive assessment of the BrS substrate, as SAECG-LPs could be considered an expression of the abnormal epicardial electrical activity.ClinicalTrials.gov number (NCT02641431; NCT03106701).
A chromosomal-level genome assembly for the giant African snail Achatina fulica
Authors: Guo Yunhai , Zhang Yi , Liu Qin , Huang Yun , Mao Guangyao , Yue Zhiyuan , Abe Eniola M , Li Jian , Wu Zhongdao , Li Shizhu , Zhou Xiaonong , Hu Wei , Xiao Ning 
Published: October 2019

Abstract

Background
Achatina fulica, the giant African snail, is the largest terrestrial mollusk species. Owing to its voracious appetite, wide environmental adaptability, high growth rate, and reproductive capacity, it has become an invasive species across the world, mainly in Southeast Asia, Japan, the western Pacific islands, and China. This pest can damage agricultural crops and is an intermediate host of many parasites that can threaten human health. However, genomic information of A. fulica remains limited, hindering genetic and genomic studies for invasion control and management of the species.

Findings
Using a k-mer–based method, we estimated the A. fulica genome size to be 2.12 Gb, with a high repeat content up to 71%. Roughly 101.6 Gb genomic long-read data of A. fulica were generated from the Pacific Biosciences sequencing platform and assembled to produce a first A. fulica genome of 1.85 Gb with a contig N50 length of 726 kb. Using contact information from the Hi-C sequencing data, we successfully anchored 99.32% contig sequences into 31 chromosomes, leading to the final contig and scaffold N50 length of 721 kb and 59.6 Mb, respectively. The continuity, completeness, and accuracy were evaluated by genome comparison with other mollusk genomes, BUSCO assessment, and genomic read mapping. A total of 23,726 protein-coding genes were predicted from the assembled genome, among which 96.34% of the genes were functionally annotated. The phylogenetic analysis using whole-genome protein-coding genes revealed that A. fulica separated from a common ancestor with Biomphalaria glabrata ~182 million years ago.

Conclusion
To our knowledge, the A. fulica genome is the first terrestrial mollusk genome published to date. The chromosome sequence of A. fulica will provide the research community with a valuable resource for population genetics and environmental adaptation studies for the species, as well as investigations of the chromosome-level of evolution within mollusks.
Effect of a dual enteric and respiratory pathogen challenge on swine growth, efficiency, carcass composition, and pork quality1
Authors: Outhouse Amanda C , Helm Emma T , Patterson Brian M , Dekkers Jack C M , Rauw Wendy M , Schwartz Kent J , Gabler Nicholas K , Huff-Lonergan Elisabeth , Lonergan Steven M 
Published: October 2019

Abstract
The objective of this study was to determine the influence of a dual respiratory and enteric pathogen challenge on growth performance, carcass composition, and pork quality of high and low feed efficient pigs. Pigs divergently selected for low and high residual feed intake (RFI, ~68 kg) from the 11th generation of Iowa State University RFI project were used to represent high and low feed efficiency. To elicit a dual pathogen challenge, half of the pigs (n = 12/line) were inoculated with Mycoplasma hyopneumoniae (Mh) and Lawsonia intracellularis (MhLI) on days post-inoculation (dpi) 0. Pigs in a separate room of the barn were not inoculated and used as controls (n = 12/RFI line). Pigs were weighed and feed intake was recorded to calculate ADG, ADFI, and G:F for the acclimation period (period 1: dpi −21 to 0), during peak infection (period 2: dpi 0 to 42), and during the remaining growth period to reach market weight (period 3: dpi 42 to harvest). At ~125 kg, pigs were harvested using standard commercial procedures. Carcasses were evaluated for composition (weight, fat free lean, loin eye area, 10th rib fat depth) and meat quality (pH decline, temperature decline, Hunter L, a, and b, subjective color and marbling, star probe, drip loss, cook loss, proximate composition, and desmin degradation). Challenged pigs had lesser ADFI than controls during period 2 (P &lt; 0.05), but had greater ADG and G:F during period 3 (P &lt; 0.05). Selection for feed efficiency did not result in a differential response to MhLI (P &gt; 0.05). Loin chops from the less feed efficient, high RFI pigs, had greater drip loss, greater cook loss, lesser moisture content, greater Hunter L values, and greater Hunter b values (P &lt; 0.05) than loin chops from low RFI pigs. Infection status did not significantly affect carcass composition or pork quality traits (P &gt; 0.05). These results indicate that a MhLI challenge early in growth did not significantly affect ultimate carcass composition or meat quality traits. Selection for greater feed efficiency in pigs did not affect their response to pathogenic challenge.
Brassinosteroids act as a positive regulator of NBR1-dependent selective autophagy in response to chilling stress in tomato
Authors: Chi Cheng , Li Xiaomeng , Fang Pingping , Xia Xiaojian , Shi Kai , Zhou Yanhong , Zhou Jie , Yu Jingquan 
Published: October 2019

Abstract
Autophagy is a highly conserved and regulated catabolic process involved in the degradation of protein aggregates, which plays critical roles in eukaryotes. In plants, multiple molecular processes can induce or suppress autophagy but the mechanism of its regulation by phytohormones is poorly understood. Brassinosteroids (BRs) are steroid phytohormones that play crucial roles in plant response to stresses. Here, we investigate the role of BRs in NBR1-dependent selective autophagy in response to chilling stress in tomato. BRs and their signaling element BZR1 can induce autophagy and accumulation of the selective autophagy receptor NBR1 in tomato under chilling stress. Cold increased the stability of BZR1, which was promoted by BRs. Cold- and BR-induced increased BZR1 stability activated the transcription of several autophagy-related genes (ATGs) and NBR1 genes by directly binding to their promoters, which resulted in selective autophagy. Furthermore, silencing of these ATGs or NBR1 genes resulted in a decreased accumulation of several functional proteins and an increased accumulation of ubiquitinated proteins, subsequently compromising BR-induced cold tolerance. These results strongly suggest that BRs regulate NBR1-dependent selective autophagy in a BZR1-dependent manner in response to chilling stress in tomato.
CIRCADIAN CLOCK ASSOCIATED 1 and ATAF2 differentially suppress cytochrome P450-mediated brassinosteroid inactivation
Authors: Peng Hao , Neff Michael M 
Published: October 2019

AbstractBrassinosteroids (BRs) are a group of steroid hormones regulating plant growth and development. Since BRs do not undergo transport among plant tissues, their metabolism is tightly regulated by transcription factors (TFs) and feedback loops. BAS1 (CYP734A1, formerly CYP72B1) and SOB7 (CYP72C1) are two BR-inactivating cytochrome P450s identified in Arabidopsis thaliana. We previously found that a TF ATAF2 (ANAC081) suppresses BAS1 and SOB7 expression by binding to the Evening Element (EE) and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1)-binding site (CBS) on their promoters. Both the EE and CBS are known binding targets of the circadian regulatory protein CCA1. Here, we confirm that CCA1 binds the EE and CBS motifs on BAS1 and SOB7 promoters, respectively. Elevated accumulations of BAS1 and SOB7 transcripts in the CCA1 null mutant cca1-1 indicate that CCA1 is a repressor of their expression. When compared with either cca1-1 or the ATAF2 null mutant ataf2-2, the cca1-1 ataf2-2 double mutant shows higher SOB7 transcript accumulations and a stronger BR-insensitive phenotype of hypocotyl elongation in white light. CCA1 interacts with ATAF2 at both DNA–protein and protein–protein levels. ATAF2, BAS1, and SOB7 are all circadian regulated with distinct expression patterns. These results demonstrate that CCA1 and ATAF2 differentially suppress BAS1- and SOB7-mediated BR inactivation.
Hot disk of the Swift J0243.6+6124 revealed by Insight-HXMT
Authors: Doroshenko V , Zhang S N , Santangelo A , Ji L , Tsygankov S , Mushtukov A , Qu L J , Zhang S , Ge M Y , Chen Y P , Bu Q C , Cao X L , Chang Z , Chen G , Chen L , Chen T X , Chen Y , Chen Y B , Cui W , Cui W W , Deng J K , Dong Y W , Du Y Y , Fu M X , Gao G H , Gao H , Gao M , Gu Y D , Guan J , Guo C C , Han D W , Hu W , Huang Y , Huo J , Jia S M , Jiang L H , Jiang W C , Jin J , Jin Y J , Kong L D , Li B , Li C K , Li G , Li M S , Li T P , Li W , Li X , Li X B , Li X F , Li Y G , Li Z J , Li Z W , Liang X H , Liao J Y , Liu C Z , Liu G Q , Liu H W , Liu S Z , Liu X J , Liu Y , Liu Y N , Lu B , Lu F J , Lu X F , Luo T , Ma X , Meng B , Nang Y , Nie J Y , Ou G , Sai N , Song L M , Song X Y , Sun L , Tan Y , Tao L , Tuo Y L , Wang G F , Wang J , Wang W S , Wang Y S , Wen X Y , Wu B B , Wu M , Xiao G C , Xiong S L , Xu H , Xu Y P , Yang Y R , Yang J W , Yang S , Yang Y J , Zhang A M , Zhang C L , Zhang C M , Zhang F , Zhang H M , Zhang J , Zhang Q , Zhang T , Zhang W , Zhang W C , Zhang W Z , Zhang Y , Zhang Y , Zhang Y F , Zhang Y J , Zhang Z , Zhang Z L , Zhao H S , Zhao J L , Zhao X F , Zheng S J , Zhu Y , Zhu Y X , Zou C L 
Published: October 2019

Abstract
We report on analysis of observations of the bright transient X-ray pulsar Swift J0243.6+6124 obtained during its 2017-2018 giant outburst with Insight-HXMT, NuSTAR, and Swift observatories. We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields.
Predicting fully self-consistent satellite richness, galaxy growth and starformation rates from the STastical sEmi-Empirical modeL steel.
Authors: Grylls Philip J , Shankar F , Leja J , Menci N , Moster B , Behroozi P , Zanisi L 
Published: October 2019

Abstract
Observational systematics complicate comparisons with theoretical models limiting understanding of galaxy evolution. In particular, different empirical determinations of the stellar mass function imply distinct mappings between the galaxy and halo masses, leading to diverse galaxy evolutionary tracks. Using our state-of-the-art STatistical sEmi-Empirical modeL, steel, we show fully self-consistent models capable of generating galaxy growth histories that simultaneously and closely agree with the latest data on satellite richness and star-formation rates at multiple redshifts and environments. Central galaxy histories are generated using the central halo mass tracks from state-of-the-art statistical dark matter accretion histories coupled to abundance matching routines. We show that too flat high-mass slopes in the input stellar-mass-halo-mass relations as predicted by previous works, imply non-physical stellar mass growth histories weaker than those implied by satellite accretion alone. Our best-fit models reproduce the satellite distributions at the largest masses and highest redshifts probed, the latest data on star formation rates and its bi-modality in the local Universe, and the correct fraction of ellipticals. Our results are important to predict robust and self-consistent stellar-mass-halo-mass relations and to generate reliable galaxy mock catalogues for the next generations of extra-galactic surveys such as Euclid and LSST.
The effect of pulsation on the near-ultraviolet spectrum of AGB stars
Authors: Guerrero Martín A , Ortiz Roberto 
Published: October 2019

ABSTRACT
Pulsating and non-pulsating asymptotic giant branch (AGB) stars exhibit a variable near-ultraviolet (near-UV) spectrum, which suggest that mechanisms other than pulsation may affect their near-UV spectrum. In this work, we analyse the near-UV spectra of two groups of AGB stars: (1) regularly pulsating and (2) irregular, small-amplitude stars. Near-UV and blue spectra were obtained for 27 stars distributed into these two groups with the Isaac Newton Telescope (La Palma, Spain). Additional near-UV spectra were taken from the iue library. The occurrence of Fe ii lines depends mainly on the intensity of the stellar continuum: as it increases, Fe ii lines are gradually hampered. Balmer emission lines are pulsation driven, as they appear only among the large-amplitude pulsating stars of our sample, between −0.10 &lt; ϕ &lt; 0.50. Among the regularly pulsating stars, the intensity of the Mg ii λ2800 doublet is driven by pulsation, with its maximum between 0.20 &lt; ϕ &lt; 0.35. On the other hand, this feature is also highly variable among small-amplitude, irregularly pulsating stars. This suggests that, besides pulsation, other mechanisms may participate in the formation of this line. The spectral slope between 3000 &lt; λ(Å)&lt;3200 is approximately constant among small-amplitude stars, but it shows a strong correlation with the phase of the pulsation in the other group, which indicates that the origin of the continuum is chromospheric. Different phase lags between the Mg ii λ2800 and the slope of the continuum suggests that this line and its neighbouring continuum might be formed in distinct places in the chromosphere or its surroundings.