633 research outputs found
Contribution of the Residual Body in the Spatial Organization of Toxoplasma gondii Tachyzoites within the Parasitophorous Vacuole
Toxoplasma gondii proliferates and organizes within a parasitophorous vacuole in rosettes around a residual body and is surrounded by a membranous nanotubular network whose function remains unclear. Here, we characterized structure and function of the residual body in intracellular tachyzoites of the RH strain. Our data showed the residual body as a body limited by a membrane formed during proliferation of tachyzoites probably through the secretion of components and a pinching event of the membrane at the posterior end. It contributes in the intravacuolar parasite organization by the membrane connection between the tachyzoites posterior end and the residual body membrane to give place to the rosette conformation. Radial distribution of parasites in rosettes favors an efficient exteriorization. Absence of the network and presence of atypical residual bodies in a ÎGRA2-HXGPRT knock-out mutant affected the intravacuolar organization of tachyzoites and their exteriorization
Point Source Detection with Fully-Convolutional Networks: Performance in Realistic Simulations
Point sources (PS) are one of the main contaminants to the recovery of the
cosmic microwave background (CMB) signal at small scales, and their detection
is important for the next generation of CMB experiments. We develop a method
(PoSeIDoN) based on fully convolutional networks to detect PS in realistic
simulations, and we compare its performance against one of the most used PS
detection method, the Mexican hat wavelet 2 (MHW2). We produce realistic
simulations of PS taking into account contaminating signals as the CMB, the
cosmic infrared background, the Galactic thermal emission, the thermal
Sunyaev-Zel'dovich effect, and the instrumental and PS shot noises. We first
produce a set of training simulations at 217 GHz to train the network. Then we
apply both PoSeIDoN and the MHW2 to recover the PS in the validating
simulations at all 143, 217, and 353 GHz, comparing the results by estimating
the reliability, completeness, and flux density accuracy and by computing the
receiver operating characteristic curves. In the extra-galactic region with a
30{\deg} galactic cut, the network successfully recovers PS at 90% completeness
corresponding to 253, 126, and 250 mJy for 143, 217, and 353 GHz respectively.
The MHW2 with a 3 flux density detection limit recovers PS up to 181,
102, and 153 mJy at 90% completeness. In all cases PoSeIDoN produces a much
lower number of spurious sources with respect to MHW2. The results on spurious
sources for both techniques worsen when reducing the galactic cut to 10{\deg}.
Our results suggest that using neural networks is a very promising approach for
detecting PS, providing overall better results in dealing with spurious sources
with respect to usual filtering approaches. Moreover, PoSeIDoN gives
competitive results even at nearby frequencies where the network was not
trained.Comment: 12 pages, 6 figures, accepted Astronomy & Astrophysic
The TRPM8 antagonist RGM8-51 displays analgesic activity in different pain models
TRPM8 channels are overexpressed in sensory neurons after nerve injury or
inflammation, resulting in enhanced sensitivity (allodynia and hyperalgesia) to physical
stimulation, and have been implicated in migraine, but the interest of TRPM8 antagonists
is still a matter of controversy (1,2). The aim of our work was to evaluate the analgesic
activity of a TRPM8 antagonist, RGM8-51, in different pain models, looking for
similarities and differences with other antagonists. To this end, we used the mouse
oxaliplatin-induced peripheral neuropathy, the chronic constriction injury of the rat
sciatic nerve (CCI) and mouse NTG-induced migraine-like models. Compound RGM8-
51 reduces the cold allodynia induced by oxaliplatin, from 15 to 60 min after
administration (0.1-1 ÎŒg, i.pl.), decreases the nocifensive responses to cold, heat and
mechanical stimuli in the CCI model (10 ÎŒg, i.pl., 30 mg/Kg, i.p.), and relief chronic pain
associated to migraine in mouse, in a sex-dependent manner (10 or 30 mg/Kg, i.v.). The
ÎČâlactam derivative RGM8-51 not only has analgesic activity in all assayed animal
models, but also seems to have a different mode of interaction with the TRPM8 channel
than other antagonists, as suggested by docking studies
Contribution of the Residual Body in the Spatial Organization of Toxoplasma gondii Tachyzoites within the Parasitophorous Vacuole
properly cited. Toxoplasma gondii proliferates and organizes within a parasitophorous vacuole in rosettes around a residual body and is surrounded by a membranous nanotubular network whose function remains unclear. Here, we characterized structure and function of the residual body in intracellular tachyzoites of the RH strain. Our data showed the residual body as a body limited by a membrane formed during proliferation of tachyzoites probably through the secretion of components and a pinching event of the membrane at the posterior end. It contributes in the intravacuolar parasite organization by the membrane connection between the tachyzoites posterior end and the residual body membrane to give place to the rosette conformation. Radial distribution of parasites in rosettes favors an efficient exteriorization. Absence of the network and presence of atypical residual bodies in a ÎGRA2-HXGPRT knock-out mutant affected the intravacuolar organization of tachyzoites and their exteriorization
DD04107-Derived neuronal exocytosis inhibitor peptides: Evidences for synaptotagmin-1 as a putative target
The analgesic peptide DD04107 (Pal-EEMQRR-NH2) and its acetylated analogue inhibit a-calcitonin gene-related peptide (a-CGRP) exocytotic release from primary sensory neurons. Examining the crystal structure of the SNARE-Synaptotagmin-1(Syt1) complex, we hypothesized that these peptides could inhibit neuronal exocytosis by binding to Syt1, hampering at least partially its interaction with the SNARE complex. To address this hypothesis, we first interrogate the role of individual side-chains on the inhibition of a-CGRP release, finding that E1, M3, Q4 and R6 residues were crucial for activity. CD and NMR conformational analysis showed that linear peptides have tendency to adopt a-helical conformations, but the results with cyclic analogues indicated that this secondary structure is not needed for activity. Isothermal titration calorimetry (ITC) measurements demonstrate a direct interaction of some of these peptides with Syt1-C2B domain, but not with Syt7-C2B region, indicating selectivity. As expected for a compound able to inhibit a-CGRP release, cyclic peptide derivative Pal-E-cyclo[EMQK]R-NH2 showed potent in vivo analgesic activity, in a model of inflammatory pain. Molecular dynamics simulations provided a model consistent with KD values for the interaction of peptides with Syt1-C2B domain, and with their biological activity. Altogether, these results identify Syt1 as a potential new analgesic target. © 202
Synthesis of Hierarchical Dorsal Spine Ag
Silver sulfide hierarchical structures with unique dorsal spine morphology were successfully synthesized on mechanically deformed silver substrates by simple solid-vapor reactions. It has been found that it is possible to change the structures morphology by changing the reagent gas composition. The carbon monoxide (CO) presence in a reactive sulfur atmosphere was found to be the key for growing the dorsal spine structures. In all cases, the Ag2S structures grew on the edge of the silver substrates where high plastic deformation occurred
Long-term effect of 2 intensive statin regimens on treatment and incidence of cardiovascular events in familial hypercholesterolemia : The SAFEHEART study
Funding: This study was supported by FundaciĂłn Hipercolesterolemia Familiar; Grant G03/181 Grant 08-2008 Centro Nacional de Investigaci?n Cardiovascular (CNIC).Background: Maximal doses of potent statins are the basement of treatment of familial hypercholesterolemia (FH). Little is known about the use of different statin regimens in FH. Objectives: The objectives of the study were to describe the treatment changes and low-density lipoprotein cholesterol (LDL-C) goal achievement with atorvastatin (ATV) and rosuvastatin (RV) in the SAFEHEART cohort, as well as to analyze the incidence of atherosclerotic cardiovascular events (ACVEs) and changes in the cardiovascular risk. Methods: SAFEHEART is a prospective follow-up nationwide cohort study in a molecularly defined FH population. The patients were contacted on a yearly basis to obtain relevant changes in life habits, medication, and ACVEs. Results: A total of 1939 patients were analyzed. Median follow-up was 6.6 years (5-10). The estimated 10-year risk according the SAFEHEART risk equation was 1.61 (0.67-3.39) and 1.22 (0.54-2.93) at enrollment for ATV and RV, respectively (P <.001). There were no significant differences at the follow-up: 1.29 (0.54-2.82) and 1.22 (0.54-2.76) in the ATV and RV groups, respectively (P =.51). Sixteen percent of patients in primary prevention with ATV and 18% with RV achieved an LDL-C <100 mg/dL and 4% in secondary prevention with ATV and 5% with RV achieved an LDL-C <70 mg/dL. The use of ezetimibe was marginally greater in the RV group. One hundred sixty ACVEs occurred during follow-up, being its incidence rate 1.1 events/100 patient-years in the ATV group and 1.2 in the RV group (P =.58). Conclusion: ATV and RV are 2 high-potency statins widely used in FH. Although the reduction in LDL-C levels was greater with RV than with ATV, the superiority of RV for reducing ACVEs was not demonstrated
Association of Body Mass Index With Clinical Outcomes in Patients With Atrial Fibrillation: A Report From the FANTASIIA Registry
Background Obesity and atrial fibrillation (AF) frequently coexist and independently increase mortality. We sought to assess the association between obesity and adverse events in patients receiving oral anticoagulants for AF. Methods and Results Consecutive AF outpatients receiving anticoagulant agents (both vitamin K antagonists and direct oral anticoagulants) were recruited into the FANTASIIA (Atrial fibrillation: influence of the level and type of anticoagulation on the incidence of ischemic and hemorrhagic stroke) registry. This observational, multicenter, and prospective registry of AF patients analyzes the quality of anticoagulation, incidence of events, and differences between oral anticoagulant therapies. We analyzed baseline patient characteristics according to body mass index, normal: <25 kg/m2, overweight: 25-30 kg/m2, and obese: â„30 kg/m2), assessing allâcause mortality, stroke, major bleeding and major adverse cardiovascular events (a composite of ischemic stroke, myocardial infarction, and total mortality) at 3 years' followâup. In this secondary prespecified substudy, the association of weight on prognosis was evaluated. We recruited 1956 patients (56% men, mean age 73.8±9.4 years): 358 (18.3%) had normal body mass index, 871 (44.5%) were overweight, and 727 (37.2%) were obese. Obese patients were younger (P<0.01) and had more comorbidities. Mean time in the therapeutic range was similar across body mass index categories (P=0.42). After a median followâup of 1070 days, 255 patients died (13%), 45 had a stroke (2.3%), 146 a major bleeding episode (7.5%) and 168 a major adverse cardiovascular event (8.6%). Event rates were similar between groups for total mortality (P=0.29), stroke (P=0.90), major bleeding (P=0.31), and major adverse cardiovascular events (P=0.24). On multivariate Cox analysis, body mass index was not independently associated with allâcause mortality, cardiovascular mortality, stroke, major bleeding, or major adverse cardiovascular events. Conclusions In this prospective cohort of patients anticoagulated for AF, obesity was highly prevalent and was associated with more comorbidities, but not with poor prognosis
Evaluation of an Electrocoagulation Process Modified by Fenton Reagent
This article is oriented to the degradation of nickel in an ionic state at laboratory level from synthetic water made with nickel sulfate, using the electrocoagulation process with aluminum cathodes and modifying this process by the addition of the Fenton reagent, which results from the combination of hydrogen peroxide (H2O2) and ferrous sulfate (FeSO4) being this reagent a catalyst and oxo-coagulant agent, The efficiency of this reagent will be compared with the typical treatment with aluminum sulfate, which is a typical process based on ion exchange/coagulation at the same percentage concentrations as the Fenton reagent. For this purpose, the optimum conditions of the advanced electrocoagulation process were determined, which consisted of determining the concentrations of Fentonâs reagent at concentrations of 150 ppm, 300 ppm, and 450 ppm, in addition to the operating variables such as pH of 8 and 10, voltage of 17.5 V and 19 V and their reaction time, which were compared with aluminum sulfate at 300 ppm, 600 ppm, and 900 ppm. The results obtained with respect to the typical treatment were 0% nickel degradation. However, with the advanced oxidation treatment, an average reduction of 97.5% was found at the conditions of 19 V, pH 10, and Fenton 150 ppm in a time of 30 min
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