Interactions of human acetylcholinesterase with phenyl valerate and acetylthiocholine: Thiocholine as an enhancer of phenyl valerate esterase activity

Phenyl valerate (PV) is a neutral substrate for measuring the PVase activity of neuropathy target esterase (NTE), a key molecular event of organophosphorus-induced delayed neuropathy. This substrate has been used to discriminate and identify other proteins with esterase activity and potential targets of organophosphorus (OP) binding. A protein with PVase activity in chicken (model for delayed neurotoxicity) was identified as butyr ylcholinesterase (BChE). Further studies in human BChE suggest that other sites might be involved in PVase activity. From the theoretical docking analysis, other more favorable sites for binding PV related to the Asn289 residue located far from the catalytic site (“PVsite”) were deduced.In this paper, we demonstrate that acetyl cholinesterase is also able to hydrolyze PV. Robust kinetic studies of interactions between substrates PV and acetylthiocholine (AtCh) were performed. The kinetics did not fit the classic competition models among sub strates. While PV interacts as a competitive inhibitor in AChE activity, AtCh at low concentrations enhances PVase activity and inhibits this activity at high concentrations. Kinetic behavior suggests that the potentiation effect is caused by thiocholine released at the active site, where AtCh could act as a Trojan Horse. We conclude that the products released at the active site could play an important role in the hydrolysis reactions of different substrates in biological systems

Social comparison processes and catastrophising in fibromyalgia:A path analysis

Introduction: In addition to coping strategies, social comparison may play a role in illness adjustment. However, little is known about the role of contrast and identification in social comparison in adaptation to fibromyalgia.Aim: To evaluate through a path analysis in a sample of fibromyalgia patients, the association between identification and contrast in social comparison, catastrophising and specific health outcomes (fibromyalgia illness impact and psychological distress).Material and Method: 131 Spanish fibromyalgia outpatients (mean age: 50.15, SD=11.1) filled out a questionnaire.Results: We present a model that explained 33% of the variance in catastrophising by direct effects of more use of upward contrast and downward identification. In addition, 35% of fibromyalgia illness impact variance was explained by less upward identification, more upward contrast and more catastrophising and 42% of the variance in psychological distress by a direct effect of more use of upward contrast together with higher fibromyalgia illness impact.Discussion: We suggest that intervention programmes with chronic pain and fibromyalgia patients should focus on enhancing the use of upward identification in social comparison, and on minimising the use of upward contrast and downward identification in social comparison

Compressive Review about Taxol: History and Future Challenges

© 2020. The authors. This document is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the Published version of a Published Work that appeared in final form in Molecules. To access the final edited and published work see DOI: 10.3390/molecules25245986Taxol®, which is also known as paclitaxel, is a chemotherapeutic agent widely used to treat different cancers. Since the discovery of its antitumoral activity, Taxol® has been used to treat over one million patients, making it one of the most widely employed antitumoral drugs. Taxol® was the first microtubule targeting agent described in the literature, with its main mechanism of action consisting of the disruption of microtubule dynamics, thus inducing mitotic arrest and cell death. However, secondary mechanisms for achieving apoptosis have also been demonstrated. Despite its wide use, Taxol® has certain disadvantages. The main challenges facing Taxol® are the need to find an environmentally sustainable production method based on the use of microorganisms, increase its bioavailability without exerting adverse effects on the health of patients and minimize the resistance presented by a high percentage of cells treated with paclitaxel. This review details, in a succinct manner, the main aspects of this important drug, from its discovery to the present day. We highlight the main challenges that must be faced in the coming years, in order to increase the effectiveness of Taxol® as an anticancer agent

Searching for dark-matter waves with PPTA and QUIJOTE pulsar polarimetry

The polarization of photons emitted by astrophysical sources might be altered as they travel through a dark matter medium composed of ultra light axion-like particles (ALPs). In particular, the coherent oscillations of the ALP background in the galactic halo induce a periodic change on the polarization of the electromagnetic radiation emitted by local sources such as pulsars. Building up on previous works, we develop a new, more robust, analysis based on the generalised Lomb-Scargle periodogram to search for this periodic signal in the emission of the Crab supernova remnant observed by the QUIJOTE MFI instrument and 20 galactic pulsars from the Parkes Pulsar Timing Array (PPTA) project. We also carefully take into account the stochastic nature of the axion field, an effect often overlooked in previous works. This refined analysis leads to the strongest limits on the axion-photon coupling for a wide range of dark matter masses spanning $10^{-23}\text{ eV}\lesssim m_a\lesssim10^{-19} \text{ eV}$. Finally, we survey possible optimal targets and the potential sensitivity to axionic dark-matter in this mass range that could be achieved using pulsar polarimetry in the future

Factors Controlling Properties of Ca-Mg, Ca-Er, Ca-Nd, or Ca-Y-Modified Aluminosilicate Glasses Containing Nitrogen and Fluorine

Glasses with composition (in eq.%) (30 − x)Ca:xM:55Si:15Al:80O:15N:5F have been prepared with different levels of substitution of Ca2+ cations by Mg2+, Y3+, Er3+, or Nd3+. The properties of these glasses are examined in detail and changes observed in molar volume (MV), free volume, fractional glass compactness, Young's modulus, microhardness, glass transition temperature, and thermal expansion as a function of M content are presented. Using linear regression analysis, evidence is presented which clearly shows that these glass properties are either solely dependent on the effective cation field strength, if modifier cation valency is the same (e.g., Mg substitution for Ca), or dependent on the effective cation field strength and the number of (Si, Al) (O, N, F) tetrahedra associated with each modifier when Ca is replaced by the trivalent modifiers. Combining these correlations with those observed previously relating glass properties to N and F substitution for O, it becomes apparent that glass properties for Ca–M–Si–Al–O–N–F glasses can be described by correlations which involve independent, but additive contributions by N and F substitution levels, effective cation field strength, and the number of tetrahedra associated with each modifier ion

Properties of Ca–(Y)–Si–Al–O–N–F Glasses: Independent and Additive Effects of Fluorine and Nitrogen

Thirty glasses of composition (in equivalent percent) 20-xCa:xY:50Si:30Al:(100-y-z)O:yN:zF, with x = 0, 10; y = 0, 10, 20, and z = 0, 1, 3, 5, 7 were prepared by melting and casting. All glasses were X-ray amorphous. Glass molar volumes (MV) decreased with nitrogen substitution for oxygen for all fluorine contents and, correspondingly, glass fractional compactness increased. Fluorine substitution of oxygen had virtually no effect on molar volume or fractional glass compactness for the three nitrogen contents tested. Young's modulus and microhardness were virtually unaffected by fluorine substitution for oxygen while nitrogen substitution for oxygen caused increases in these two properties. Glass-transition temperature and dilatometric-softening point values all decreased with increasing fluorine substitution levels, while increasing nitrogen substitution caused values for these thermal properties to increase. Correspondingly, the thermal expansion coefficient increased with fluorine and decreased with nitrogen substitution levels. Using property value differences between glasses containing fluorine and the corresponding glass containing 0 eq.% F enabled 24 data points to be used to determine the effect of fluorine on Tg,dil and TDS. The trends were linear with a gradient for both properties of the order of −22°C (eq.% F)−1. For the nitrogen effect, 20 data points were analyzed for trend effects. As expected from earlier work, all trends had good linearity. Gradients were for Tg,dil and TDS +2.5°C (eq.% N)−1, which are fairly similar to previous results in oxynitride systems. All of the data collected and its analysis clearly shows that the substitution effects of fluorine for oxygen and nitrogen for oxygen are independent and additive with the fluorine substitution. The property trends of the glasses are discussed in terms of their implications for glass structure.The authors wish to acknowledge Science Foundation Ireland and Valencian Small and Medium Enterprise Institute for financial support of this research and to thank colleagues in Materials Ireland and the Materials and Surface Science Institute for their help and advice

La agricultura ecológica a largo plazo en plantaciones de cítricos permite la recuperación del carbono orgánico del suelo

[ES] Se ha demostrado que el manejo del suelo bajo agricultura ecológica puede aumentar el contenido de carbono orgánico en el suelo moderando el incremento de los gases de efecto invernadero, pero hasta la fecha las evaluaciones cuantitativas basadas en mediciones a largo plazo han sido escasas, especialmente bajo condiciones mediterráneas. En esta investigación se examinaron los cambios en el contenido de carbono orgánico como respuesta a la agricultura ecológica con cobertura vegetal en una plantación de cítricos en el área mediterránea, utilizando una base de datos de 21 años. El incremento de contenido de carbono orgánico en el suelo fue más evidente tras cinco años desde el cambio del manejo del suelo, sugiriendo que, para plantaciones de cítricos en ambientes mediterráneos, los estudios deberían tener una duración superior a cinco años. La sata de secuestro de carbono orgánico no cambió significativamente durante los 21 años de observaciones, con valores que oscilaron entre -1.10 Mg C ha-1 a-1 y 1.89 Mg C ha-1 a-1. Tras 21 años, un total de 61 t CO2 ha-1 fueron secuestradas en las áreas de acumulación de carbono en el suelo. Estos resultados demuestran que la agricultura ecológica es una estrategia efectiva para restaurar o incrementar los niveles de carbono orgánico en el suelo en los sistemas de cítricos mediterráneos.[EN] It has been shown that soil management under organic farming can enhance soil organic carbon, thereby mitigating atmospheric greenhouse gas increases, but until now quantitative evaluations based on long term experiments are scarce, especially under Mediterranean conditions. Changes in soil organic carbon (SOC) content were examined in response to organic management with cover crops in a Mediterranean citrus plantation using 21 years of survey data. Soil organic carbon increase was more apparent 5 years after a land management change suggesting that, for citrus plantations on Mediterranean conditions, studies should be longer than five years in duration. Soil organic carbon sequestration rate did not significantly change during the 21 years of observation, with values ranging from -1.10 Mg C ha(-1) y(-1) to 1.89 Mg C ha(-1) y(-1). After 21 years, 61 Mg CO2 ha(-1) were sequestered in long-lived soil C pools. These findings demonstrate that organic management is an effective strategy to restore or increase SOC content in Mediterranean citrus systems.This research was funded by the European Union Seventh Framework Program (FP7/2007-2013) under grant no. 603498 (RECARE Project) and the research projects GL2008-02879/BTE and LEDDRA 243857.Novara, A.; Pulido, M.; Rodrigo-Comino, J.; Di Prima, S.; Smith, P.; Gristina, L.; Giménez Morera, A.... (2019). Long-term organic farming on a citrus plantation results in soil organic carbon recovery. Cuadernos de Investigación Geográfica. 45(1):271-286. https://doi.org/10.18172/cig.3794S27128645

Data preprocessing workflow for exhaled breath analysis by GC/MS using open sources

© 2020 The Authors. This document is made available under the CC-BY 4.0 license. http://creativecommons.org/licenses/by /4.0/ This document is the Accepted version of a Published Work that appeared in final form in Scientifc Reports. To access the final edited and published work see https://doi.org/10.1038/s41598-020-79014-

Tillage versus no-tillage. soil properties and hydrology in an organic persimmon farm in eastern Iberian Peninsula

There is an urgent need to implement environmentally friendly agriculture management practices to achieve the Sustainable Goals for Development (SDGs) of the United Nations by 2030. Mediterranean agriculture is characterized by intense and millennia-old tillage management and as a consequence degraded soil. No-Tillage has been widely examined as a solution for soil degradation but No-Tillage relies more on the application of herbicides that reduce plant cover, which in turn enhances soil erosion. However, No-Tillage with weed cover should be researched to promote organic farming and sustainable agriculture. Therefore, we compare Tillage against No-Tillage using weed cover as an alternative strategy to reduce soil losses in persimmon plantations, both of them under organic farming management. To achieve these goals, two plots were established at "La Canyadeta" experimental station on 25-years old Persimmon plantations, which are managed with Tillage and No-Tillage for 3 years. A survey of the soil cover, soil properties, runoff generation and initial soil losses using rainfall simulation experiments at 55 mm h-1 in 0.25 m2 plot was carried out. Soils under Tillage are bare (96.7%) in comparison to the No-Tillage (16.17% bare soil), with similar organic matter (1.71 vs. 1.88%) and with lower bulk densities (1.23 vs. 1.37 g cm3). Tillage induces faster ponding (60 vs. 92 s), runoff (90 vs. 320 s) and runoff outlet (200 vs. 70 s). The runoff discharge was 5.57 times higher in the Tillage plots, 8.64 for sediment concentration and 48.4 for soil losses. We conclude that No-tillage shifted the fate of the tilled field after 3 years with the use of weeds as a soil cover conservation strategy. This immediate effect of No-Tillage under organic farming conditions is very promising to achieve the SDGs

Cardiac Function and Serum Biomarkers throughout Staged Fontan Palliation:A Prospective Observational Study

Fontan patients undergo multiple cardiothoracic surgeries in childhood. Following these procedures, ventricular function is temporarily decreased, and recovers over months. This is presumably related to cardiopulmonary bypass, but this is incompletely understood. Throughout the Fontan palliation, cardiac function is also affected by volume unloading. We aimed to gain insight into the biological processes related to impaired ventricular function and recovery following Fontan palliations using a panel of biomarkers. Furthermore, we described changes in ventricular function across the Fontan palliation due to volume unloading. We performed a prospective multicenter observational study in patients undergoing partial (PCPC) or total cavo-pulmonary connection (TCPC). Patients underwent assessment-including echocardiography and blood sampling-before surgery (T1), at first follow-up (T2), and 1 year after their procedures (T3). Blood samples were analyzed using a biomarker panel (OLINK CVD-III). Ninety-two biomarkers were expressed as principal components (PC) to limit multiple statistical testing. We included 32 PCPC patients aged 7.2 [5.3-10.3] months, and 28 TCPC patients aged 2.7 [2.2-3.8] years. The single ventricular longitudinal strain (SV GLS) temporarily decreased for PCPC patients at T2 (-15.1 ± 5.6 (T1) to -13.5 ± 5.2 (T2) to -17.3 ± 4.5 (T3), p &lt; 0.047 for all differences), but not following TCPC. The serum biomarkers were expressed as 4 PCs. PC1, including biomarkers of cell-cell adhesion, was not related to any patient characteristic. PC2, including biomarkers of superoxide anion regulation, increased at T2. PC3, including biomarkers of cardiovascular development, related to the stage of Fontan palliation. PC4 was of uncertain biological or clinical significance. No PC was found that related to ventricular performance. The SV GLS was temporarily diminished following PCPC, but not following TCPC. Several biomarkers were related to post-operative stress and adaptation to the PCPC or TCPC circulation, but none were related to the outcome. </p