Broad emission lines in quasars enable us to “resolve” structure and kinematics of the broad-line emitting region (BLR) thought to involve an accretion disk feeding a supermassive black hole. ...Interpretation of broad line measures within the 4DE1 formalism simplifies the apparent confusion among such data by contrasting and unifying properties of so-called high and low accreting Population A and B sources. Hβ serves as an estimator of black hole mass, Eddington ratio and source rest frame; the latter being a valuable input for Civλ1549 studies which allow us to isolate the blueshifted wind component. Optical and HST-UV spectra yield Hβ and Civλ1549 spectra for low-luminosity sources while VLT-ISAAC and FORS and TNG-LRS provide spectra for high-luminosity sources. New high-S/N data for Civ in high-luminosity quasars are presented here for comparison with the other previously published data. Comparison of Hβ and Civλ1549 profile widths/shifts indicates that much of the emission from the two lines arise in regions with different structure and kinematics. Covering a wide range of luminosity and redshift shows evidence for a correlation between Civλ1549 blueshift and source Eddington ratio, with a weaker trend with source luminosity (similar amplitude outflows are seen over four of the five dex luminosity ranges in our combined samples). At low luminosity (z ≲ 0.7) only Population A sources show evidence for a significant outflow while at high luminosity the outflow signature begins to appear in Population B quasars as well.
•A novel approach for endocrine-disrupting chemicals determination in mussels.•Development of a matrix solid phase dispersion methodology for mussel samples.•Simultaneous separation and ...quantification of 11 EDCs by HPLC-DAD.•Limits of quantification ranged between 0.25 and 16.20 µg/Kg.
A new matrix solid-phase dispersion (MSPD) extraction methodology, combined with high-performance liquid chromatography equipped with a diode-array detector, was developed and validated for the simultaneous determination of 10 compounds in mussels from Galician Rias (Spain). These pollutants are compounds commonly used for plastic production as additives, as well as common plastic contaminants. The compounds selected were bisphenol-A, bisphenol-F, bisphenol-S, nonylphenol-9, nonylphenol, diethyl phthalate, dibutyl phthalate, di-2-ethylhexyl phthalate, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethane, and dichlorodiphenyldichloroethylene. The parameters affecting the MSPD extraction efficiency such as the type of sorbent, mass sample-sorbent ratio, and extraction solvent were optimised. The proposed method provided satisfactory quantitative recoveries (80–100%), with relative standard deviations lower than 7%. In all cases, the matrix-matched calibration curves were linear in the concentration range of 0.32–120.00 µg/kg, with quantification limits of 0.25–16.20 µg/kg. The novel developed MSPD-high-performance liquid chromatography methodology provided good sensitivity, accuracy, and repeatability for quality control analysis in mussels.
Base excision repair (BER) generates gapped DNA intermediates containing a 5′-terminal 2-deoxyribose-5-phosphate (5′-dRP) group. In mammalian cells, gap filling and dRP removal are catalyzed by Pol ...β, which belongs to the X family of DNA polymerases. In higher plants, the only member of the X family of DNA polymerases is Pol λ. Although it is generally believed that plant Pol λ participates in BER, there is limited experimental evidence for this hypothesis. Here we have characterized the biochemical properties of
Arabidopsis thaliana
Pol λ (AtPol λ) in a BER context, using a variety of DNA repair intermediates. We have found that AtPol λ performs gap filling inserting the correct nucleotide, and that the rate of nucleotide incorporation is higher in substrates containing a C in the template strand. Gap filling catalyzed by AtPol λ is most efficient with a phosphate at the 5′-end of the gap and is not inhibited by the presence of a 5′-dRP mimic. We also show that AtPol λ possesses an intrinsic dRP lyase activity that is reduced by mutations at two lysine residues in its 8-kDa domain, one of which is present in Pol λ exclusively and not in any Pol β homolog. Importantly, we also found that the dRP lyase activity of AtPol λ allows efficient completion of uracil repair in a reconstituted short-patch BER reaction. These results suggest that AtPol λ plays an important role in plant BER.
Key message
Pol λ, the only X family DNA polymerase present in plants, possesses a dRP lyase activity that is required for completion of base excision repair in
Arabidopsis
.
In the last years, several scientific studies have shown that carbamazepine (CBZ) is one of the most frequently detected pharmaceutical in aquatic environment. However, little data is available on ...its detection and its transformation products (TPs) in marine water. The use of polar organic chemical integrative sampling (POCIS) passive samplers as a semi-quantitative and qualitative tool for screening of pharmaceuticals and TPs in seawater has been studied. Furthermore, the uptake rates of the target compounds were also determined under laboratory experiments to characterize the levels accumulated in devices. The results confirmed the presence of residues of anticonvulsant CBZ as well as some of its main metabolites, over a 1-year monitoring campaign carried out in French coast on the Mediterranean Sea. The work reports for the first time the presence of two TPs (10,11-dihydro-10,11-trans-dihydroxycarbamazepine (TRANS) and 10-hydroxy-10,11-dihydrocarbamazepine (10OH)) in marine water. The results contribute in assessing the environmental and human health risk of pharmaceuticals on coastal areas.
Nowadays, combined oral contraceptives (COCs) are successfully employed for the treatment of endometriosis (END) and adenomyosis (AD) in a large proportion of patients. However, literature focusing ...on the clinical and sonographic response to treatment in the long-term follow-up of patients with deep endometriosis (DE) and AD is scarce. The aim of this study was to evaluate the changes in the symptoms and the sonographic exams at 12 and 24 months of follow-up in patients who had received a flexible extended COC regimen containing 2 mg of dienogest/30 μg ethinyl estradiol. This prospective, longitudinal, observational study included women diagnosed with DE and AD presenting no surgical indication and were candidates to treatment with COCs. The presence and severity of dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria were evaluated using the Numerical Rating Scale (NRS) at baseline, and at 12 and 24 months of treatment. Transvaginal ultrasound was also performed at these check points searching for criteria of AD and reporting the size of the DE nodules and ovarian endometriomas (OE). Sixty-four patients were included. A significant decrease in the number of patients with severe dysmenorrhea and non-menstrual pelvic pain was reported during follow-up. The mean NRS score for dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria was also significantly lower at follow-up. There was a significant reduction in the sonographic number and type of AD criteria during follow-up after treatment. Similarly, a significant decrease in the size of OE and uterosacral ligament involvement in DE was observed at the 12-month follow-up, with a further, albeit not statistically significant, decrease in the 12- to 24-month follow-up. Additionally, torus and rectosigmoid DE decreased in size, although the reduction was not statistically significant at any study point. This prospective study suggests a clinical and sonographic improvement after a flexible extended COC regimen in DE and AD patients, which was significant at 12 months of follow-up. The improvement was more evident in AD and OEs compared with DE. Further research with a longer follow-up, larger sample size and comparison with other treatments is needed.
Under pathological conditions, microglia, the resident CNS immune cells, become reactive and release pro-inflammatory cytokines and neurotoxic factors. We investigated whether this phenotypic switch ...includes changes in the expression of the L-type voltage-gated calcium channel (VGCC) in a rat model of N-methyl-d-aspartate-induced hippocampal neurodegeneration. Double immunohistochemistry and confocal microscopy evidenced that activated microglia express the L-type VGCC. We then analyzed whether BV2 microglia express functional L-type VGCC, and investigated the latter's role in microglial cytokine release and phagocytic capacity. Activated BV2 microglia express the CaV1.2 and CaV1.3 subunits of the L-type VGCC determined by reverse transcription-polymerase chain reaction, Western blot and immunocytochemistry. Depolarization with KCl induced a Ca2+ entry facilitated by Bay k8644 and partially blocked with nifedipine, which also reduced TNF-α and NO release by 40%. However, no nifedipine effect on BV2 microglia viability or phagocytic capacity was observed. Our results suggest that in CNS inflammatory processes, the L-type VGCC plays a specific role in the control of microglial secretory activity.
•Reactive microglial from hippocampus express α1 subunits of the L-type VGCC in vivo and in vitro.•Nifedipine and Bay k8644 modulate intracellular calcium concentration of reactive BV2 microglia.•L-type VGCC participates in the control of the pro-inflammatory activity of microglia.
The adiposity invokes innate immune activity, coronary microvascular dysfunction and consequently heart failure preserved ejection fraction (HFpEF). Our aim was to study the neutrophils profile on ...obesity and cardiovascular disease and its regulation by adipose tissue‐secretome and dapagliflozin. We have isolated neutrophils from patients undergoing open heart surgery (19 women and 51 men). Its migration activity was performed with culture‐transwell, transcriptional studies of proteolytic enzymes, adhesion molecules or receptors were analysed by real‐time PCR and proteomics (from 20 patients) analysis by TripleTOF mass spectrometer. Differentiated HL‐60 (dHL‐60) was used as a preclinical model on microfluidic for endothelial cells attaching assays and genes regulation with epicardial and subcutaneous fat secretomes from patients (3 women and 9 men) or dapagliflozin 1–10 μM treatments. The transcriptional and proteomics studies have determined higher levels of adhesion molecules in neutrophils from patients with obesity. The adhesion molecule CD11b levels were higher in those patients with the combined obesity and HFpEF factors (1.70 ± 0.06 a.u. without obesity, 1.72 ± 0.04 a.u. obesity or HFpEF without obesity and 1.79 ± 0.08 a.u. obesity and HFpEF; p < .01). While fat‐secretome induces its upregulation, dapagliflozin can modulated it. Because CD11b upregulation is associated with higher neutrophils migration and adhesion into endothelial cells, dapagliflozin might modulate this mechanism on patients with obesity and HFpEF.
We aimed to evaluate the utility of the FreeStyle Libre 2 device for reducing time below range level 1 and level 2 compared with the Freestyle Libre device (without alarms) in people with type 1 ...diabetes mellitus. We conducted longitudinal observational follow-up study of a cohort of 100 people with type 1 diabetes mellitus who had switched from FreeStyle Libre to FreeStyle Libre 2 as part of routine clinical practice. Three months after switching to FreeStyle Libre 2, compared with results with FreeStyle Libre, there were a significant improvements in time below range level 1 (p = 0.02) and level 2 (p <0.001), time in range (p <0.001), time above range level 1 (p = 0.002), glucose management indicator (p= 0.04) and mean glucose (p= 0.04) during follow-up. Furthermore there was a significant direct association between age and change in TIR with a coefficient of 0.23, and a significant inverse association between age and change in TAR-1 with a coefficient of 0.11. Switching to a flash glucose monitoring system with alarms improves time below range, time in range and coefficient of variation in people with type 1 diabetes mellitus.
•Study of switching from isCGM to isCGM with alarms in people with type 1 diabetes.•Time below range level 1 and 2 decreased significantly with isCGM with alarms use.•isCGM with alarms use improved time in range and time above range 1 significantly.•Baseline HbA1c was associated with changes in coefficient of variation.•Age was associated with changes in time above range level 1 and time in range.
Novel coordination compounds, mono‐ (1) and binuclear copper complexes (2) and a zinc complex (3) were synthesized and studied through single‐crystal X‐ray crystallography, solid‐state NMR and EPR ...techniques to determine the chemical functionalization of the carbonyl group in N‐methyl‐2‐imidazolecarboxaldehyde ligand. Particularly, molecules containing carbonyl groups are versatile ligands that give rise to a wide range of new materials due to the high reactivity of the carbonyl group. However, the chemical identification of the functional group present in these coordination compounds is a challenge because the copper ion affects the NMR signals. In this sense, X‐ray crystallography becomes an indispensable tool for the analysis. The imidazole ligands in copper complexes 1 and 2 were found to be the aldehyde and the gem‐diol forms, respectively. Furthermore, the gem‐diol and carboxylate moieties were detected in the crystal lattice for the zinc complex 3 and studied by solution‐ and solid‐state NMR.
Mono‐ (1) and binuclear copper complexes (2) and a zinc complex (3) were synthesized and studied through X‐ray crystallography, solid‐state NMR and EPR techniques to determine the chemical functionalization of the aldehyde group in N‐methyl‐2‐imidazolecarboxaldehyde. The ligands in the complexes 1, 2 and 3 were found to be the aldehyde, the gem‐diol, and both the gem‐diol and carboxylate moieties, respectively.
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