728 research outputs found

    Cdk1 and Plk1 mediate a CLASP2 Phospho-Switch that Stabilizes Kinetochore–Microtubule Attachments

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    Accurate chromosome segregation during mitosis relies on a dynamic kinetochore (KT)-microtubule (MT) interface that switches from a labile to a stable condition in response to correct MT attachments. This transition is essential to satisfy the spindle-assembly checkpoint (SAC) and couple MT-generated force with chromosome movements, but the underlying regulatory mechanism remains unclear. In this study, we show that during mitosis the MT- and KT-associated protein CLASP2 is progressively and distinctively phosphorylated by Cdk1 and Plk1 kinases, concomitant with the establishment of KT-MT attachments. CLASP2 S1234 was phosphorylated by Cdk1, which primed CLASP2 for association with Plk1. Plk1 recruitment to KTs was enhanced by CLASP2 phosphorylation on S1234. This was specifically required to stabilize KT-MT attachments important for chromosome alignment and to coordinate KT and non-KT MT dynamics necessary to maintain spindle bipolarity. CLASP2 C-terminal phosphorylation by Plk1 was also required for chromosome alignment and timely satisfaction of the SAC. We propose that Cdk1 and Plk1 mediate a fine CLASP2 phospho-switch that temporally regulates KT-MT attachment stability

    Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder in Older Adults: Systematic Review and Meta-analysis

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    Background Major depressive disorder (MDD) in older adults is a serious public health concern. Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological intervention approved for MDD treatment in adults, but its value in older adults remains unknown. This study aims to systematically review and meta-analyze evidence of rTMS efficacy in MDD treatment among older adults. Methods We systematically reviewed the literature for randomized controlled trials (RCTs) and open-label studies assessing rTMS for the treatment of MDD in patients older than 50 years, published until June 2020. Random-effects meta-analyses using standardized mean differences (SMDs) were conducted to assess change in depression severity score (primary outcome), while odds ratios (ORs) were used to assess secondary categorical outcomes (response and remission). Additionally, univariate meta-regression analyses were performed to identify potential predictors of change in depression severity scores. Results Fourteen RCTs were included in meta-analyses and 26 studies (10 RCTs and 16 open-label studies) in meta-regression. Active rTMS was significantly superior to sham treatment for reduction of severity (SMD = 0.36; 95% CI = 0.13–0.60), as well as response (OR = 3.26; 95% CI = 2.11–5.04) and remission (OR = 4.63; 95% CI = 2.24–9.55). Studies were of moderate to high quality, with funnel plots and Egger’s regression test not suggestive of publication bias. In meta-regressions, higher mean age and number of sessions were significantly associated with greater improvement. Conclusions Our results support that rTMS is an effective, safe, and well-tolerated treatment for MDD in older adults and that it should be considered in the treatment of this vulnerable population.info:eu-repo/semantics/publishedVersio

    Production de vins mousseux a partir de "Vinhos Verdes" blancs monovarietaux

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    On a fait l'étude comparative de vins mousseux élaborés à partir de vins de base issus de cinq cépages recommandés pour la Région: Loureiro, Trajadura, Avesso, Pedernã et Azal blanc, en ce qui concerne les propriétés organoleptiques. Les vins de base ont été produits selon le processus utilisé dans la Région -égrappage, pressurage, débourbage et fermentation alcoolique-, ayant été soumis aussi à une fermentation malolactique. La prise de mousse a été effectuée en bouteille, avec des levures immobilisées en billes d'alginate, pendant cinq mois à 14 °C. Les propriétés sensorielles des vins ont été évaluées en utilisant des fiches classificatrices et descriptives, par une chambre de neuf dégustateurs expérimentés. Le traitement statistique des résultats, effectué par le logiciel SPSS, a été fait en recourrant à l'analyse de variance. On a trouvé quelques différences parmi les cinq vins mousseux surtout en ce qui concerne l'aspect du cordon et l'arôme. Cependant, tous ces vins ont obtenu des classifications globales au-dessus de l'acceptable, atteignant parfois l'excellent. Ces résultats préliminaires ainsi obtenus, basés sur les caractéristiques organoleptiques, suggèrent la possibilité d'obtenir des vins mousseux de qualité à partir des cépages de "Vinho Verde"

    Chiral analysis of pesticides and drugs of environmental concern: biodegradation and enantiomeric fraction

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    The importance of stereochemistry for medicinal chemistry and pharmacology is well recognized and the dissimilar behavior of enantiomers is fully documented. Regarding the environment, the significance is equivalent since enantiomers of chiral organic pollutants can also differ in biodegradation processes and fate, as well as in ecotoxicity. This review comprises designed biodegradation studies of several chiral drugs and pesticides followed by enantioselective analytical methodologies to accurately measure the enantiomeric fraction (EF). The enantioselective monitoring of microcosms and laboratory-scale experiments with different environmental matrices is herein reported. Thus, this review focuses on the importance of evaluating the EF variation during biodegradation studies of chiral pharmaceuticals, drugs of abuse, and agrochemicals and has implications for the understanding of the environmental fate of chiral pollutants.info:eu-repo/semantics/publishedVersio

    Solid Phase Extraction of Fluoroquinolone Antibiotics from Wastewaters – Assessment of Different Commercial Sorbents

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    Microbial degradation of fluorinated pharmaceuticals during wastewater treatment processes remains inadequate in most situations. Due to incomplete elimination, these residues are continually being introduced into the aquatic environments in which they settle throughout time since many of them are resistant to degradation. Fluoroquinolone antibiotics due to its persistence and implication on resistant-bacteria development, pose special interest in environmental analysis. Due to their zwitterionic characteristics, the extraction/pre-concentration process of fluoroquinolones prior analyses is an unquestionable challenge. This work compares the solid phase extraction efficiency of four fluoroquinolones (Ofloxacin, Norfloxacin, Ciprofloxacin and Moxifloxacin) from wastewater effluents by different commercial sorbents. Prior to wastewater analysis, preliminary tests were conducted in distilled water with a larger number of sorbents. Different experimental protocols and sorbents, namely OASIS® HLB, OASIS® WAX, OASIS® WCX (500 mg) and the molecularly imprinted polymer SupelMIP TM were applied to wastewater samples collected from a municipal wastewater treatment plant from the north of Portugal. The extracts were analyzed by a HPLC withFluorescence Detection validated method using a Luna PFP (2) 3µm column. Despite good results obtained with the molecularly imprinted polymer in distilled water, these cartridges did not perform efficiently when applied to wastewater effluents, probably due to the sample high complexity especially since their specific design for biological samples. Regarding OASIS® considered sorbents; HLB 500mg and WAX 500mg presented the best recovery rates of the fourstudied antibiotics, between 84-75% and 64-94%, respectively. Although the recoveries achievedwere not that dissimilar between the two mentioned sorbents, chromatograms of WAX extracts appear much cleaner in the antibiotics retention times while chromatograms of HLB extractsclearly show the presence of strong polar substances, probably matrix humic and fulvic acids,that behave as resilient interferences in the analysis, disturbing a proper identification of target compounds and reducing chromatographic resolution

    Interviewing Peter Gow — Dundee, June 24, 2017

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    This interview presents an initial dialogue about Peter Gow’s trajectory as an anthropologist, trying to bring to light particularly the fieldwork experiences and events that it had not been possible to commenton and explore in the published material. Its aim is to understand more closely the particular ways in which Peter Gow had come to arrive at the insights and the analyses presented in his brilliant ethnographies with the Yine/Piro people of Amazonia

    Development and Optimization of an Online SPE-HPLC-FD Method for Quantification of Fluoroquinolones in Wastewater Effluents

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    Fluoroquinolones are antimicrobial agents widely found in environmental matrices and extensively studied due to their persistence and implications for multiresistant bacteria. The presence of fluoroquinolones in the environment is mainly due to the incapability of wastewater treatment plants (WWTPs) to completely remove those compounds. The amount of fluoroquinolones released through effluents depends on the type of treatment used by the WWTPs. So, accurate analytical methods to quantify those compounds on WWTPs process and in effluents are crucial. Solid phase extraction (SPE) coupled to liquid chromatography is a straightforward technique that provides analyte extraction, cleanup, separation and detection while providing a good reproducibility and efficiency. The purpose of this work was the establishment of a novel method for quantification of Ofloxacin, Norfloxacin, Ciprofloxacin and Moxifloxacin on WWTPs effluents using on-line SPE. Samples were injected directly on a restricted access material column LichroCart 25-4 Lichrospher® RP-18 ADS (25 μm) and then transferred to an analytical column Luna PFP (2) (150 x 4.6 mm ID, 100 Å, 3 μm) for separation in isocratic mode with a mixture of 0.1% triethylamine in water (acidified to pH = 2.2 with trifluoroacetic acid) and ethanol as mobile phase; column oven was set at 45ºC. The detection was performed by fluorescence with an excitation wavelength of 290 nm and an emission wavelength of 460 nm. The injection volume of 100 μL of previous preconcentrated sample was compared with larger volume injection of only filtered effluent samples. The study was conducted with effluent samples collected from a municipal WWTP in the north of Portugal

    A Review of This Enzyme Role in the Intestinal Barrier Function

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    Funding Information: This study was supported by ERDF through the operation POCI-01-0145-ERDF-007746 funded by Programa Operacional Competitividade e Internacionaliza??o?COMPETE2020 and by National Funds through FCT?Funda??o para a Ci?ncia e a Tecnologia within CINTESIS, R&D Unit (reference UID/IC/4255/2013) and (PTDC/BAA-AGR/7419/2020).Intestinal alkaline phosphatase (IALP) has recently assumed a special relevance, being the subject of study in the prevention and treatment of certain diseases related to leaky gut. This brush border enzyme (ecto-enzyme) plays an important role in the maintenance of intestinal microbial homeostasis and intestinal barrier function through its ability to dephosphorylate lipopolysaccharide (LPS). This review addresses how IALP and intestinal barrier dysfunction may be implicated in the pathophysiology of specific diseases such as inflammatory bowel disease, necrotizing enterocolitis, and metabolic syndrome. The use of IALP as a possible biomarker to assess intestinal barrier function and strategies to modulate IALP activity are also discussed.publishersversionpublishe

    Enantioselective Determination of Fluoxetine and Norfluoxetine in Wastewater

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    Microbial degradation of chiral compounds during wastewater treatment processes can be enantioselective and needs chiral analytical methodology to discriminate the biodegradation of both enantiomers. An enantioselective HPLC-FD method was developed and validated to monitor the degradation of fluoxetine (FLX) enantiomers by wastewater and the possible formation of its metabolite norfluoxetine (NFLX). The Solid Phase Extraction (SPE) of 50 mL of wastewater samples on 500 mg Oasis MCX cartridges was followed by the HPLC analysis using a Chirobiotic V chiral stationary phase under reversed mode. The developed method wasvalidated within the wastewater effluent used in microcosms laboratory assays. The chiral SPE-HPLC-FD method demonstrated to be selective, linear, sensitive, accurate and precise to quantify the enantiomers of FLX and of its metabolites NFLX in wastewaters. The limits of detection (0.8-2.0 ng mL -1 ) and quantification (2.0 – 4.0 ng mL -1 ) were adequate to monitoring the degradation assays at environmental level. The method proved to be robust to follow the biodegradation assays using real wastewater samplesspiked with FLX, during 46 days. To the best of our knowledge, this is the first reportof simultaneous separation of FLX and NFLX enantiomers using a Chirobiotic V and the application of the validated method to the enantioselective degradation by wastewate
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