Interplay Between Ni and Brønsted and Lewis Acid Sites in the Hydrodesulfurization of Dibenzothiophene.

Ni-MoS2/γ-Al2O3 catalysts are commonly used in hydrotreating to enhance fossil fuel quality. The extensive research on these catalysts reveals a gap in understanding the role of Ni, often underestimated as an inactive sulfide phase or just a MoS2 promoter. In this work, we focused on analyzing whether well-dispersed supported nickel nanoparticles can be active in the hydrodesulfurization of dibenzothiophene. We dispersed Ni by Strong Electrostatic Adsorption (SEA) method across four supports with different types of acidity: silica (~ neutral acidity), γ-Al2O3 (Lewis acidity), H+-Y zeolite, and microporous-mesoporous H+-Y zeolite (both with Brønsted-Lewis acidity). Our findings reveal that Ni is indeed active in dibenzothiophene hydrodesulfurization, even with alumina and silica as supports, although their catalytic activity declines abruptly in the first hours. Contrastingly, the acid nature of zeolites imparts sustained stability and performance, attributed to robust metal-support interactions. The efficacy of the SEA method and the added mesoporosity in zeolites further amplify catalytic efficiency. Overall, we demonstrate that Ni nanoparticles may perform as a hydrogenating metal in the same manner as noble metals such as Pt and Pd perform in hydrodesulfurization. We discuss some of the probable reasons for such performance and remark on the role of Ni in hydrotreatment.

Nickel(II)-Catalyzed Formal [3+2] Cycloadditions between Indoles and Donor-Acceptor Cyclopropanes.

This article describes the development of a nickel-catalyzed regio- and diastereoselective formal [3+2] cycloaddition between N-substituted indoles and donor-acceptor cyclopropanes to synthesize cyclopenta[b]indoles. Optimized reaction conditions provide the desired nitrogen-containing cycloadducts in up to 93% yield and dr 8.6:1 with complete regioselectivity. The substrate scope showed high tolerance to various substituted indoles and cyclopropanes, resulting in the synthesis of six new cyclopenta[b]indoles and the isolation of five derivatives previously reported in the literature. In addition, a mechanistic proposal for the reaction was studied through online reaction monitoring by ESI-MS, allowing for the identification of the reactive intermediates in the Ni(II) catalyzed process. X-ray crystallography confirmed the structure and relative endo stereochemistry of the products. This method enables the fast and efficient construction of fused indolines from readily accessible starting materials.

Exploration of the Production of Three Thiodiketopiperazines by an Endophytic Fungal Strain of Cophinforma mamane.

Endophytic fungi possess a versatile metabolism which is related to their ability to live in diverse ecological niches. While culturing under laboratory conditions, their metabolism is mainly influenced by the culture media, time of incubation and other physicochemical factors. In this study, we focused on the production of 3 thiodiketopiperazines (TDKPs) botryosulfuranols A-C produced by an endophytic strain of Cophinforma mamane isolated from the leaves of Bixa orellana L collected in the Peruvian Amazon. We studied the time-course production of botryosulfuranols A-C during 28 days and evaluated the variations in the production of secondary metabolites, including the TDKPs, produced by C. mamane in response to different culture media, light versus dark conditions and different incubation times. We observed a short time-frame production of botryosulfuranol C while its production was significantly affected by the light conditions and nutrients of the culture media. Botryosulfuranols A and B showed a similar production pattern and a similar response to culturing conditions. Molecular networking allowed us to detect three compounds related to TDKPs that will be the focus of future experiments.

P2X7-Receptor Pathway Involvement in the Anti-Inflammatory Activity of Medicinal Plants.

Medicinal plants used in European folk medicine attached to Lamiales, Gentianales or Asterales orders are used to treat inflammatory disorders. Many targets have been identified but to date, implication of purinergic receptor P2X7 activation has not yet been investigated. We managed to evaluate the protective effect on P2X7 activation by plant extracts used as anti-inflammatory in European folk medicine by the YO-PRO-1 uptake dye in vitro bioassay. Results revealed that among our selected plants, species from Scrophularia and Plantago genus were able to decrease significantly P2X7 activation (>50 % at 0.1 and 1 µg/mL). UPLC/MS, dereplication and metabolomic analysis of Scrophularia extracts, allowed us to identify the cinnamoyl-iridoid harpagoside as putative inhibitor of P2X7 activation. These results open a new research field regarding the anti-inflammatory mechanism of cinnamoyl-iridoids bearing plants, which may involve the P2X7 receptor.

Enhancing c-Si Solar Cell Efficiency in the UV Region: Photophysical Insights into the Use of Eu3+ Complexes for Down-Shifting Layer Applications.

[Eu(3DPIQC)3] (where DPIQC = 3-(diphenyl phosphoryl)-1-isoquinolinecarboxylate), a luminescent europium complex with antenna ligands, has been carefully embedded within a polyvinyl butyral (PVB) matrix and the resulting material was used to prepare films used as luminescent down-shifting layers (LDSLs) for crystalline Si-based solar cells. The films were characterized using photoluminescence spectroscopy, atomic force spectroscopy (AFM), UV-Vis spectroscopy, and fluorescence microscopy. The AFM analysis shows films with low surface roughness, while fluorescence microscopy revealed that the Eu complex embedded in PVB assumed a spheroidal configuration, a morphology especially beneficial for optical applications. The so-obtained LDSLs were utilized as energy converters in c-Si solar cells to enhance the utilization of high-energy photons, thereby improving their overall efficiency. The determination of photovoltaic parameters carried out before and after the deposition of the LDSLs on the c-Si cells confirms a positive effect on the efficiency of the cell. The Jsc increases from 121.6 mA/cm2 to 124.9 mA/cm2, and the open circuit voltage (Voc) is found to be unrelated to the complex concentration in the films. The fill factor (FF) remains constant with the Eu concentration. The EQE curves indicate an enhancement in the performance of the photovoltaic cells within the UV region of the spectrum for all coated devices. Electrochemical impedance spectroscopy (EIS) was also carried out in order to analyze the effect of the Eu complex in the charge transfer process of the devices.

The relationship between carotid intima-media thickness and cognitive function and depression in postmenopausal women.

Introduction: Atherosclerosis, cognitive impairment, and depression are common entities in postmenopausal patients. Our aim was to ascertain the relationship between the carotid intima-media thickness (IMT) and cognitive function and depression in postmenopausal women. Material and methods: This was an observational, cross-sectional, comparative study among postmenopausal women. A carotid artery ultrasound was performed, and the IMT was measured. Mental function was assessed with the mini-mental state examination (MMSE), and the presence of depression with the Hamilton Depression Rating Scale (HDRS). For statistical analysis the Mann-Whitney U test and Spearman correlation were used. Sensitivity, specificity, positive predictive value, negative predictive value, and odds ratio (OR) were calculated. Results: Seventy-five patients were studied. The median of age was 52 years (31-76), and the IMT was 1.1 mm (0.6-0.20). The HDRS score was 8.9 (1-21), and that of the MMSE was 29 (18-30). After dividing the group according to the presence or absence of depression, it was found that age and IMT were greater in the group with depression, and the MMSE score was greater in the group without depression. After dividing according to the MMSE score, age and HDRS score were significantly greater in the group with cognitive impairment. The intima-media thickness had an OR of 12.2 (2.6-58.0) for cognitive impairment and an OR of 5.2 (1.9-14.1) for depression. Conclusions: The intima-media thickness is associated with greater risk of cognitive impairment and depression.

Dereplication and Quantification of Major Compounds of Convolvulus arvensis L. Extracts and Assessment of Their Effect on LPS-Activated J774 Macrophages.

Convolvulus arvensis is used in Pakistani traditional medicine to treat inflammation-related disorders. Its anti-inflammatory potential was evaluated on hexane, dichloromethane, ethyl acetate, methanol, and aqueous extracts of whole plant on pro-inflammatory mediators in LPS-activated murine macrophage J774 cells at the non-cytotoxic concentration of 50 µg/mL. Ethyl acetate (ARE) and methanol (ARM) extracts significantly decreased mRNA levels of IL-6, TNF-α, MCP-1, COX-2, and iNOS. Furthermore, both extracts dose dependently decreased IL-6, TNF-α, and MCP-1 secretion. Forty-five compounds were putatively identified in ARE and ARM by dereplication (using HPLC-UV-HRMSn analysis and molecular networking), most of them are reported for the first time in C. arvensis, as for example, nineteen phenolic derivatives. Rutin, kaempferol-3-O-rutinoside, chlorogenic acid, 3,5-di-O-caffeoylquinic acid, N-trans-p-coumaroyl-tyramine, and N-trans-feruloyl-tyramine were main constituents identified and quantified by HPLC-PDA in ARE and ARM. Furthermore, chlorogenic acid, tyramine derivatives, and the mixture of the six identified major compounds significantly decreased IL-6 secretion by LPS-activated J774 cells. The activity of N-trans-p-coumaroyl-tyramine is shown here for the first time. Our results indicate that ARE, ARM and major constituents significantly inhibited the expression of pro-inflammatory mediators, which supports the use of this plant to treat inflammatory diseases.

Pistacia lentiscus L. Distilled Leaves as a Potential Cosmeceutical Ingredient: Phytochemical Characterization, Transdermal Diffusion, and Anti-Elastase and Anti-Tyrosinase Activities.

The present work was performed to investigate the phenolic composition of P. lentiscus L. distilled leaves (PDL) and examine its potential against certain key enzymes related to skin aging. High-pressure liquid chromatography coupled to mass spectrometry (HPLC-MS) and various separation procedures combined with nuclear magnetic resonance (NMR) and MS analysis were performed to isolate and identify compounds present in the ethyl acetate extract (EAE) of PDL. A high amount of flavonol glycoside was detected in EAE. Indeed, quercetin-3-O-rhamnoside (FC), myricetin-3-O-rhamnoside (FM2), and kaempferol-3-O-rhamnoside (FB2) were isolated from EAE, and are present in high quantities of 10.47 ± 0.26, 12.17 ± 0.74, and 4.53 ± 0.59 mg/g dry weight, respectively. A transdermal diffusion study was carried out to determine the EAE-molecules that may transmit the cutaneous barrier and showed that FM2 transmits the membrane barrier with a high amount followed by FC. EAE, FM2, and FC were tested against tyrosinase and elastase enzymes. Moreover, intracellular tyrosinase inhibition and cytotoxicity on skin melanoma cells (B16) were evaluated. The results indicated that EAE, FC, and FM2 have important inhibitory activities compared to the well-known standards, at non-cytotoxic concentrations. Therefore, they could be excellent agents for treating skin pigmentation and elasticity problems.

Fractionation Coupled to Molecular Networking: Towards Identification of Anthelmintic Molecules in Terminalia leiocarpa (DC.) Baill.

Terminalia leiocarpa is a medicinal plant widely used in ethnoveterinary medicine to treat digestive parasitosis whose extracts were shown to be active against gastrointestinal nematodes of domestic ruminants. The objective of our study was to identify compounds responsible for this activity. Column fractionation was performed, and the activity of the fractions was assessed in vitro on Haemonchus contortus and Caenorhabditis elegans as well as their cytotoxicity on WI38 fibroblasts. Two fractions were the most active on both nematode models and less cytotoxic. LC-MS/MS analysis and manual dereplication coupled to molecular networking allowed identification of the main compounds: ellagic acid and derivatives, gallic acid, astragalin, rutin, quinic acid, and fructose. Other potentially identified compounds such as shikimic acid, 2,3-(S)-hexahydroxydiphenoyl-D-glucose or an isomer, quercetin-3-O-(6-O-galloyl)-ß-D-galactopyranoside or an isomer, and a trihydroxylated triterpenoid bearing a sugar as rosamultin are reported in this plant for the first time. Evaluation of the anthelmintic activity of the available major compounds showed that ellagic and gallic acids were the most effective in inhibiting the viability of C. elegans. Their quantification in fractions 8 and 9 indicated the presence of about 8.6 and 7.1 µg/mg ellagic acid and about 9.6 and 2.0 µg/mg gallic acid respectively. These concentrations are not sufficient to justify the activity observed. Ellagic acid derivatives and other compounds that were found to be positively correlated with the anthelmintic activity of the fractions may have additive or synergistic effects when combined, but other unidentified compounds could also be implicated in the observed activity.

Time-of-flight camera characterization with functional modeling for synthetic scene generation.

In this manuscript, we design, describe, and present a functional model of Time-of-Flight (ToF) cameras. The model can be used to generate randomized scenes that incorporate depth scenarios with various objects at various depths with varied orientations and illumination intensity. In addition to the potential to generate any random depth scenario, the camera, pixels, and binning are modelled incorporating radial distortion based on camera intrinsic and extrinsic. The model also includes ToF artifacts such as Signal Noise, Crosstalk and Multipath. We measured experimentally the Noise in Time-of-Flight. We experimentally fitted, and simulated with state-of-the art Simulator the Crosstalk effect, and characterized multipath according with the existing literature. Our work can be used to generate as many images as needed for neural network (NN) training and testing. The proposed approach can also be used to benchmark and evaluate both End-to-End ToF algorithms as well as specialized algorithms for denoising, unwrapping, crosstalk, and multipath correction.

Chemical Composition, Antibacterial Screening and Cytotoxic Activity of Chiliadenus antiatlanticus (Asteraceae) Essential Oil.

The chemical composition and in vitro antibacterial and cytotoxic activities of the essential oil (EO) of Chiliadenus antiatlanticus (Emb. & Maire) Gómiz, an asteraceous species endemic to the southwest of Morocco, were investigated. The EO yield was 1.07±0.28 %, twenty-seven metabolites were identified representing more than 96.4 % of the total composition. Camphor (35.7 %) and derivatives, borneol (4.9 %) and camphene (4.2 %) together with intermedeol (19.9 %), α-pinene (15.5 %) and (E)-pinocarveol (4.1 %) were the major constituents. An antibacterial activity was noticed against 24 strains (all Gram-positive) out of 71 at MICs values=100 µg/mL. The EO also showed significant toxicity towards liver HepG2 (55.8 % of cell viability) and melanoma B16 4A5 (41.6 % of cell viability) tumor cell lines at 100 µg/mL.

Chemical Composition and Biological Screening of the Essential Oils of Micromeria macrosiphon and M. arganietorum (Lamiaceae).

The chemical composition and in vitro biological activities of the essential oil (EO) of Micromeria macrosiphon Coss. and M. arganietorum (J. Emb.) R. Morales, two Lamiaceae endemic to south Morocco, were investigated. GC/MS analysis resulted in the identification of 36 metabolites from the EO of M. macrosiphon, 45 from M. arganietorum. Borneol was the major metabolite in both oils and together with related derivatives such as camphor, accounted for 2/3 of the EO of M. macrosiphon, 1/3 of those of M. arganietorum. Pinene and terpinene derivatives were also present in high proportions. From a chemotaxonomic point of view, the composition of the examined samples may be related to those of other species endemic to Macaronesia. Both EOs showed significant toxicity towards liver HepG2 and melanoma B16 4A5 tumor cell lines at 100 µg/mL; however, they were also cytotoxic towards S17 normal cell lines, with a selectivity index <1. No antibacterial activity was noticed against 52 strains at 100 µg/mL.

A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic Esters.

Pentacyclic triterpenes (PTs) are commonly found in medicinal plants with well-known antiparasitic effects. Previous research on C-3 and C-27 triterpenic esters showed effective and selective in vitro antiparasitic activities and in vivo effectiveness by parenteral routes. The aim of this study was to determine triterpenic esters' stability in different biological-like media and the main microsomal degradation products. An HPLC-PDA method was developed and validated to simultaneously analyze and quantify bioactive triterpenic esters in methanol (LOQ: 2.5 and 1.25-100 µg/mL) and plasma (LOQ: 5-125 µg/mL). Overall, both triterpenic esters showed a stable profile in aqueous and buffered solutions as well as in entire plasma, suggesting gaining access to the ester function is difficult for plasma enzymes. Conversely, after 1 h, 30% esters degradation in acidic media was observed with potential different hydrolysis mechanisms. C-3 (15 and 150 µM) and C-27 esters (150 µM) showed a relatively low hepatic microsomal metabolism (<23%) after 1 h, which was significantly higher in the lowest concentration of C-27 esters (15 µM) (>40% degradation). Metabolic HPLC-PDA-HRMS studies suggested hydrolysis, hydroxylation, dehydration, O-methylation, hydroxylation and/or the reduction of hydrolyzed derivatives, depending on the concentration and the position of the ester link. Further permeability and absorption studies are required to better define triterpenic esters pharmacokinetic and specific formulations designed to increase their oral bioavailability.

Relationship of vitamin D blood concentration with muscle mass and cognitive function in postmenopausal women.

INTRODUCTION: Low levels of vitamin D have been associated with muscle mass loss and cognitive function alteration. OBJECTIVE: To find out the relationship of vitamin D blood levels with muscle mass and cognitive function in postmenopausal women. MATERIALS AND METHODS: Ninety-nine postmenopausal women aged ≥ 50 years were studied. Calf circumference, and tricipital, bicipital, subscapular and suprailiac skinfolds were measured. Arm muscle area, bone-free arm muscle area, and muscle mass were calculated. The short physical performance battery (SPPB) was performed, and the sarcopenia rapid diagnostic questionnaire (SARC-F), as well as the Mini Mental State Examination (MMSE) were applied. A blood sample was taken to measure vitamin D blood concentration. For statistical analysis, Mann-Whitney's U-test and Spearman's correlation analysis were used. RESULTS: It was found that, the older the age, the higher the vitamin D levels, as well as higher SARC-F score. Vitamin D levels were negatively correlated with grip strength and SPPB. There was a negative correlation between vitamin D levels and MMSE global score. CONCLUSIONS: Vitamin D did not have a positive influence on muscle mass. A better MMSE performance was observed in those with lower vitamin D levels.

INTRODUCCIÓN: Las concentraciones bajas de vitamina D se han asociado con la pérdida de masa muscular y la alteración de la función cognitiva. OBJETIVO: Conocer la relación de la concentración sanguínea de vitamina D con la masa muscular y la función cognitiva en mujeres posmenopáusicas. MATERIALES Y MÉTODOS: Se estudiaron 99 mujeres posmenopáusicas ≥ 50 años. Se midió la circunferencia de la pantorrilla, los pliegues cutáneos tricipital, bicipital, subescapular y suprailíaco. Se calcularon: el área muscular del brazo, el área muscular libre de hueso y la masa muscular total. Se realizó la prueba corta de desempeño físico (PCDF), se aplicó el cuestionario de diagnóstico rápido de sarcopenia (SARC-F) y el Mini Examen del Estado Mental (MMSE). Se tomó una muestra de sangre para medir la concentración de vitamina D en sangre. Para el análisis estadístico se utilizó la prueba U de Mann-Whitney y análisis de correlación de Spearman. RESULTADOS: Se encontró que a mayor edad hubieron mayores concentraciones de vitamina D y mayor puntaje SARC-F. Las concentraciones de vitamina D se correlacionaron negativamente con la fuerza de agarre, la PCDF y la puntuación total del MMSE. CONCLUSIONES: La vitamina D no tuvo una influencia positiva sobre la masa muscular. Se observó un mejor desempeño en el MMSE en aquellas con concentraciones más bajas de vitamina D.

Correlation study on methoxylation pattern of flavonoids and their heme-targeted antiplasmodial activity.

A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomimetic MS assay and in vitro antiplasmodial activity on two strains of P. falciparum. Stability of heme adducts was discussed using the dissociation voltage at 50% (DV50). No correlation was observed between the methoxylation pattern and the antiparasitic activity, either for the 3D7 chloroquine-sensitive or for the W2 chloroquine-resistant P. falciparum strains. However, in each PMF family an increased DV50 was observed for the derivatives methoxylated in position 5. Measurement of intra-erythrocytic hemozoin formation of selected derivatives was performed and hemozoin concentration was inversely correlated with heme-binding affinity. Kaempferol showed no influence on hemozoin formation, reinforcing the hypothesis that this compound may exert in vitro antiplasmodial activity mostly through other pathways. Pentamethoxyquercetin has simultaneously demonstrated a significant biological activity and a strong interaction with heme, suggesting that inhibition of hemozoin formation is totally or partially responsible for its antiparasitic effect.

Nondestructive nanostraw intracellular sampling for longitudinal cell monitoring.

Here, we report a method for time-resolved, longitudinal extraction and quantitative measurement of intracellular proteins and mRNA from a variety of cell types. Cytosolic contents were repeatedly sampled from the same cell or population of cells for more than 5 d through a cell-culture substrate, incorporating hollow 150-nm-diameter nanostraws (NS) within a defined sampling region. Once extracted, the cellular contents were analyzed with conventional methods, including fluorescence, enzymatic assays (ELISA), and quantitative real-time PCR. This process was nondestructive with >95% cell viability after sampling, enabling long-term analysis. It is important to note that the measured quantities from the cell extract were found to constitute a statistically significant representation of the actual contents within the cells. Of 48 mRNA sequences analyzed from a population of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs), 41 were accurately quantified. The NS platform samples from a select subpopulation of cells within a larger culture, allowing native cell-to-cell contact and communication even during vigorous activity such as cardiomyocyte beating. This platform was applied both to cell lines and to primary cells, including CHO cells, hiPSC-CMs, and human astrocytes derived in 3D cortical spheroids. By tracking the same cell or group of cells over time, this method offers an avenue to understand dynamic cell behavior, including processes such as induced pluripotency and differentiation.

Relationship of the neutrophil/lymphocyte ratio with cardiovascular risk markers in premenopausal and postmenopausal women.

INTRODUCTION: Cardiovascular disease is more frequent in postmenopausal women. Atherosclerosis is associated with inflammation and the neutrophil/lymphocyte ratio (NLR) is a marker of inflammation whose behavior in postmenopause is unknown. AIM OF THE STUDY: To know the relationship of the NLR with cardiovascular risk markers in premenopausal and postmenopausal women. MATERIAL AND METHODS: Premenopausal and postmenopausal women were studied, in all of them a complete hemogram and the NLR, platelet/lymphocyte ratio (PLR) were calculated, also glucose and lipids levels were measured. In all of them subcutaneous and visceral fat, carotid intima-media thickness (IMT), epicardial fat were measured by ultrasound Also baseline and and after flow-mediated stimulus the arterial diameter, the pulsatility index and the resistive index of the brachial artery were measured by ultrasound. The results are reported with medians and intervals, Mann-Whitney U and Spearman correlation analysis were performed. RESULTS: Eighty two patients were recruited, 41 premenopausal and 41 postmenopausal. When comparing both groups there was no difference in glucose, lipids, NLR, PLR, carotid IMT, epicardial fat, subcutaneous fat, visceral fat or Doppler parameters of the brachial artery. CONCLUSION: NLR was not different between premenopausal and postmenopausal women but abnormal PLR was greater in those postmenopausal with vasomotor symptoms.

Efecto de la frecuencia de aplicación de estrógenos locales sobre el grosor endometrial en mujeres posmenopáusicas.

INTRODUCTION: Conjugated estrogens, when used by the vaginal route for the relief of vaginal dryness and atrophy, can produce endometrial changes. OBJECTIVE: To know the effect of vaginal conjugated estrogens application frequency on endometrial thickness in postmenopausal women. METHOD: Seventy postmenopausal women with vaginal dryness who received conjugated estrogen cream (0.625 mg/1 g) for 12 weeks were studied. The women were divided according to application frequency as follows: group 1, twice-weekly (n = 35), and group 2, thrice-weekly (n = 35). At baseline and at end-of-treatment, vaginal cytology was examined to determine the estrogenic value, and an endovaginal ultrasound was performed to measure endometrial thickness. The comparison between groups was carried out with Mann Whitney's U-test, and the comparison between baseline and post-treatment values, with Wilcoxon's test. RESULTS: Of 70 recruited women, only 38 were studied, 19 in each group, paired by baseline estrogenic value. No difference was found between groups, neither at baseline nor after treatment, in the maturation index, estrogenic value or endometrial thickness. CONCLUSION: There were no differences in endometrial thickness between the conjugate estrogen cream different application frequencies.

INTRODUCCIÓN: Los estrógenos conjugados vía vaginal para aliviar la atrofia y sequedad vaginales pueden producir cambios endometriales. OBJETIVO: Conocer el efecto de la frecuencia de aplicación de estrógenos conjugados vía vaginal en el grosor endometrial en mujeres posmenopáusicas. MÉTODO: Se estudiaron 70 mujeres posmenopáusicas con sequedad vaginal que recibieron estrógenos conjugados en crema (0.625 mg/1 g) durante 12 semanas divididas de la siguiente manera según la frecuencia de aplicación: grupo 1, dos veces por semana (n = 35) y grupo 2, tres veces por semana (n = 35). Al inicio y final del tratamiento se determinó el valor estrogénico en la citología vaginal y se realizó ultrasonido endovaginal para medir el grosor endometrial. La comparación entre los grupos se realizó con U de Mann-Whitney y entre los valores pre y postratamiento con prueba de Wilcoxon. RESULTADOS: De 70 mujeres reclutadas solo se estudiaron 38 mujeres, 19 en cada grupo, pareadas por valor estrogénico inicial. No se encontró diferencia entre los grupos, ni antes ni después del tratamiento, en el índice de maduración, valor estrogénico ni grosor endometrial. CONCLUSIÓN: No hubo diferencias en el grosor endometrial entre las distintas frecuencias de aplicación de estrógenos conjugados en crema.

Bassoon and Piccolo maintain synapse integrity by regulating protein ubiquitination and degradation.

The presynaptic active zone (AZ) is a specialized microdomain designed for the efficient and repetitive release of neurotransmitter. Bassoon and Piccolo are two high molecular weight components of the AZ, with hypothesized roles in its assembly and structural maintenance. However, glutamatergic synapses lacking either protein exhibit relatively minor defects, presumably due to their significant functional redundancy. In the present study, we have used interference RNAs to eliminate both proteins from glutamatergic synapses, and find that they are essential for maintaining synaptic integrity. Loss of Bassoon and Piccolo leads to the aberrant degradation of multiple presynaptic proteins, culminating in synapse degeneration. This phenotype is mediated in part by the E3 ubiquitin ligase Siah1, an interacting partner of Bassoon and Piccolo whose activity is negatively regulated by their conserved zinc finger domains. Our findings demonstrate a novel role for Bassoon and Piccolo as critical regulators of presynaptic ubiquitination and proteostasis.