Asymptomatic atrial fibrillation (AF) detection and pulmonary veins isolation (PVI) outcome prediction remain challenging. Our aim was to study the association between apelin and paroxysmal AF in ...patients undergoing radiofrequency catheter PVI.
Sixty-three consecutive patients (55 ± 8years, 12 females) with paroxysmal AF without a structural heart disease and implanted ECG loop recorders undergoing PVI and healthy control group of 34 persons (41 ± 9.5years, 21 females) were included. Apelin plasmatic concentrations were measured before and three months after PVI. AF burden was continually assessed for three years.
Apelin was significantly decreased in AF patients compared to the healthy controls (0.79 ± 0.09 vs 0.98 ± 0.06 ng/ml; p < 0.00001). Apelin plasmatic concentration of 0.89 ng/ml had 94 % specificity and 89 % sensitivity for AF prediction with the area under the curve (AUC) of 0.96. After propensity matching to sex, age and comorbidities, apelin concentration was significantly lower in AF group (0.78 ± 0.1 vs 0.99 ±0.06 ng/ml; p < 0.0001; AUC: 0.97). There was a significant inverse correlation between apelin concentration and AF burden both before and after PVI (Rho = ‒0.22; p = 0.05) and (Rho = ‒0.51; p = 0.006), respectively. There was no significant association between pre-PVI apelin and PVI long-term outcome.
In patients without a structural heart disease apelin showed a significant specificity and sensitivity for AF prediction and inversely correlated with AF burden (Tab. 3, Fig. 3, Ref. 34).
Oedema factor, a calmodulin-activated adenylyl cyclase, is important in the pathogenesis of anthrax. Here we report the X-ray structures of oedema factor with and without bound calmodulin. Oedema ...factor shares no significant structural homology with mammalian adenylyl cyclases or other proteins. In the active site, 3'-deoxy-ATP and a single metal ion are well positioned for catalysis with histidine 351 as the catalytic base. This mechanism differs from the mechanism of two-metal-ion catalysis proposed for mammalian adenylyl cyclases. Four discrete regions of oedema factor form a surface that recognizes an extended conformation of calmodulin, which is very different from the collapsed conformation observed in other structures of calmodulin bound to effector peptides. On calmodulin binding, an oedema factor helical domain of relative molecular mass 15,000 undergoes a 15 A translation and a 30 degrees rotation away from the oedema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation. These allosteric changes provide the first molecular details of how calmodulin modulates one of its targets.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A detailed tephrostratigraphic record, which dates back to Marine Isotope Stage (MIS) 5b (ca. 91 kyr), has been established from a 17.76 m long core (Co1215) from Lake Prespa (Macedonia, Albania and ...Greece). A total of eleven tephra and cryptotephra layers (PT0915-1 to PT0915-11) were identified, using XRF scanning, magnetic susceptibility measurements, and macro- and microscopic inspection of the sediments. The major element composition of glass shards and/or micro-pumice fragments indicates that the tephras and cryptotephras originate from the explosive volcanism of Italy. Eight tephra and cryptotephra layers were correlated with specific volcanic eruptions: the AD 512 eruption of Somma-Vesuvius (1438 cal yr BP), the Mercato eruption of Somma-Vesuvius (8890 ± 90 cal yr BP), the Tufi Biancastri/LN1-LN2 eruption of the Campi Flegrei (14 749 ± 523 cal yr BP and 15 551 ± 621 cal yr BP), the SMP1-e/Y-3 eruption of the Campi Flegrei (30 000–31 000 cal yr BP), the Campanian Ignimbrite/Y-5 eruption of the Campi Flegrei (39 280 ± 110 cal yr BP), the SMP1-a event of Ischia Island (around 44 000 cal yr BP) and the Green Tuff/Y-6 eruption of Pantelleria Island (around 45 000 cal yr BP). One tephra could be attributed to the volcanic activity of Mount Etna, but probably represents an unknown eruption at ca. 60 000 cal yr BP. Cryptotephras PT0915-6 and PT0915-10 remain unclassified so far, but according to the presented age-depth model these would have been deposited around 35 000 and 48 500 cal yr BP, respectively. Some of the tephras and cryptotephras are recognised for the first time in the Balkan region. The tephrostratigraphic work provides important information about ash dispersal and explosion patterns of source volcanoes and can be used to correlate and date geographically distant paleoenvironmental and archaeological archives in the central Mediterranean region. Moreover, the tephrostratigraphic work in combination with radiocarbon and electron spin resonance (ESR) dating is a precondition for paleoclimatic reconstructions inferred from the sediment succession Co1215.
Ultraviolet (UV) light induces different classes of mutagenic photoproducts in DNA, namely cyclobutane pyrimidine dimers (CPDs), 6-4 photoproducts (6-4PPs), and atypical thymine-adenine photoproducts ...(TA-PPs). CPD formation is modulated by nucleosomes and transcription factors (TFs), which has important ramifications for Ultraviolet (UV) mutagenesis. How chromatin affects the formation of 6-4PPs and TA-PPs is unclear. Here, we use UV damage endonuclease-sequencing (UVDE-seq) to map these UV photoproducts across the yeast genome. Our results indicate that nucleosomes, the fundamental building block of chromatin, have opposing effects on photoproduct formation. Nucleosomes induce CPDs and 6-4PPs at outward rotational settings in nucleosomal DNA but suppress TA-PPs at these settings. Our data also indicate that DNA binding by different classes of yeast TFs causes lesion-specific hotspots of 6-4PPs or TA-PPs. For example, DNA binding by the TF Rap1 generally suppresses CPD and 6-4PP formation but induces a TA-PP hotspot. Finally, we show that 6-4PP formation is strongly induced at the binding sites of TATA-binding protein (TBP), which is correlated with higher mutation rates in UV-exposed yeast. These results indicate that the formation of 6-4PPs and TA-PPs is modulated by chromatin differently than CPDs and that this may have important implications for UV mutagenesis.
10M Ni–Mn–Ga polycrystals show a typical self-accommodated microstructure consisting of macro and micro twins. The macro twin lamellae separate micro twins creating a so-called “twins within twins” ...microstructure. Such a configuration allows the distribution of martensitic variants with no net change in shape of the sample. The arrangement of variants can occur on different length scales, from a few nanometers up to a few millimeters, not only depending on grain size but also on processing condition (e.g., extrusion, torsion). Small austenite grains do not completely transform to martensite giving rise to some residual austenite. Furthermore, characteristic branching of macro and micro twins is observed due to lowering of the elastic energy at grain and macro twin boundaries, respectively.
Data describing contemporary profile of infective endocarditis (IE) in the Czech Republic are lacking. The aim of this study was to describe the current profile and outcomes of IE patients.
...Prospectively collected data on consecutive patients admitted for IE diagnosis between April 2016 and March 2018 to 11 main tertiary care cardiac centers in the Czech Republic were used for this analysis.
Among 208 patients, 88 patients (42.3 %) had native valve IE (NVIE), 56 patients (26.9 %) had prosthetic valve IE (PVIE), and 57 patients (27.4 %) had intracardiac device-related IE (CDRIE). The mean age was 61.66±15.54 years. Staphylococcus aureus was the most common etiological agent of IE (27.4 %), whereas Culture negative IE was present in 26.4 % patients. Surgery was performed during hospitalization in 112 (53.8 %) patients. In-hospital death occurred in 21.2 % patients, while 1-year mortality was 40.3 %. In patients, who had an indication for surgery, but the procedure was not performed, mortality was significantly higher (p=0.002).
High proportion of culture negative IE and IE related to artificial intra-cardiac materials calls for action. Furthermore, we show that cardiac surgery should be more often contemplated, especially in the presence of risk factors as septic shock and congestive heart failure (Tab. 6, Fig. 1, Ref. 32).
The dopamine agonist bromocriptine has been approved for the treatment of type 2 diabetes in the United States. Bromocriptine inhibits prolactin secretion, and patients with hyperprolactinaemia ...display impaired insulin sensitivity. We therefore hypothesized that low prolactin levels are associated with lower glycaemia and higher insulin sensitivity in healthy subjects. Prolactin levels were determined from fasting serum in participants without diabetes from the cross-sectional Tübingen family study for type 2 diabetes (m/f = 562/1,121, age = 40 ± 13 years, BMI = 30 ± 9 kg/m
2
). A 75 g oral glucose tolerance test was performed, and the area under the glucose curve (AUC
0–120
Glucose) and insulin sensitivity index were calculated. A subgroup (
n
= 494) underwent hyperinsulinaemic–euglycaemic clamp tests. Prolactin associated positively with insulin sensitivity (
p
= 0.001, adjusted for gender, age, and BMI). Age strongly interacted (
p
< 0.0001) with the effect of prolactin on insulin sensitivity, inverting the positive relationship to a negative one in younger participants. Glycated haemoglobin (HbA1c) and AUC
0–120
Glucose correlated negatively with prolactin, and an interaction with age was found as well. Higher prolactin levels are associated with improved insulin sensitivity and lower glucose in individuals without diabetes. This relationship turns to its opposite in younger persons. As prolactin is a proxy for the dopaminergic tone in the central nervous system, these associations may indicate an age-dependent influence of the brain on peripheral insulin sensitivity.
Polyadenylation of eukaryotic mRNAs contributes to stability, transport and translation, and is catalyzed by a large complex of conserved proteins. The Pcf11 subunit of the yeast CF IA factor ...functions as a scaffold for the processing machinery during the termination and polyadenylation of transcripts. Its partner, Clp1, is needed for mRNA processing, but its precise molecular role has remained enigmatic. We show that Clp1 interacts with the Cleavage-Polyadenylation Factor (CPF) through its N-terminal and central domains, and thus provides cross-factor connections within the processing complex. Clp1 is known to bind ATP, consistent with the reported RNA kinase activity of human Clp1. However, substitution of conserved amino acids in the ATP-binding site did not affect cell growth, suggesting that the essential function of yeast Clp1 does not involve ATP hydrolysis. Surprisingly, non-viable mutations predicted to displace ATP did not affect ATP binding but disturbed the Clp1-Pcf11 interaction. In support of the importance of this interaction, a mutation in Pcf11 that disrupts the Clp1 contact caused defects in growth, 3′-end processing and transcription termination. These results define Clp1 as a bridge between CF IA and CPF and indicate that the Clp1-Pcf11 interaction is modulated by amino acids in the conserved ATP-binding site of Clp1.
Context. Aims. We derive rotation curves from optical emission lines of 182 disc galaxies (96 in the cluster and 86 in the field) in the region of Abell 901/902 located at z ~ 0.165. We continue the ...kinematic analysis presented in a previous paper. Here, we focus on the analysis of B-band and stellar-mass Tully-Fisher relations. We examine possible environmental dependencies and differences between normal spirals and dusty red galaxies, i.e. disc galaxies that have red colours because of relatively low star formation rates. Methods. Assuming a tilted ring model we simulate the spectroscopy of a given galaxy and reconstruct the maximum rotation velocity from the best-fitting simulated rotation curve. We fit regression lines adopting a maximum-likelihood method based on Bayes’ theorem to build B-band and stellar-mass Tully-Fisher relations. Results. We find no significant differences between the best-fit Tully-Fisher slope of cluster and field galaxies. At fixed slope, the field population with high-quality rotation curves (57 objects) is brighter by ΔMB = −0.m42 ± 0.m15 than the cluster population (55 objects). We show that this slight difference is at least in part an environmental effect. The scatter of the cluster Tully-Fisher relation increases for galaxies closer to the core region, also indicating an environmental effect. Interestingly, dusty red galaxies become fainter towards the core at a given rotation velocity (i.e. total mass). This indicates that the star formation in these galaxies is in the process of being quenched. The luminosities of normal spiral galaxies are slightly higher at fixed rotation velocity for smaller cluster-centric radii. These galaxies are probably gas-rich (compared to the dusty red population) and the onset of ram-pressure stripping increases their star-formation rates. Galaxies with smooth morphology show higher root mean square values in the fitting of their rotation curves. This is particularly the case for dusty red galaxies. A cluster-specific interaction process like ram-pressure stripping is the best explanation, since it only affects the gaseous disc but not the stellar morphology. Conclusions. The results from the Tully-Fisher analysis are consistent with and complement our previous findings. Dusty red galaxies might be an intermediate stage in the transformation of infalling field spiral galaxies into cluster lenticulars (also known as S0s), and this might explain the well-known increase of the S0 fraction in galaxy clusters with cosmic time.
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