Enteral Feeding: Brain-Visceral Interactions in the Processing of Nutrients

Enteral nutrition is often mandatory, especially for patients in vegetative or minimally conscious state. However, its application is nonviable in certain cases due to various adverse effects. Some of these are explained by absence of the cephalic phase of digestion, during which exocrine, endocrine, and motor physiological responses prepare the digestive system to receive, digest, transform, and utilize ingested nutrients. These responses result from the stimulation by nutrients of cephalic sensory systems, mainly in the oropharyngeal cavity, and can also be elicited by food-related thoughts or expectations. The digestive system appears able to rapidly assess the suitability of food and transmit this information to the brain. The vagus nerve and its brainstem relays in the caudal nucleus of the solitary tract (NST) and parabrachial complex appear to participate in the anatomic pathway responsible for this rapid processing. Thus, blockade of the vagus nerve, NST, or external lateral parabrachial region (LPBe) interrupts expression of conditioned taste preferences induced by administration of “predigested” food, while LPBe activation by electric stimulation generates similar preferences to those observed after cephalic food administration. This review may help design enteral diets better adapted to digestive physiology and develop pharmacological interventions against adverse effects of enteral nutrition

Design, synthesis and structure-activity evaluation of novel 2-pyridone-based inhibitors of a-synuclein aggregation with potentially improved BBB permeability

The treatment of Parkinson''s disease (PD), the second most common neurodegenerative human disorder, continues to be symptomatic. Development of drugs able to stop or at least slowdown PD progression would benefit several million people worldwide. SynuClean-D is a low molecular weight 2-pyridone-based promising drug candidate that inhibits the aggregation of a-synuclein in human cultured cells and prevents degeneration of dopaminergic neurons in a Caenorhabditis elegans model of PD. Improving SynuClean-D pharmacokinetic/pharmacodynamic properties, performing structure/activity studies and testing its efficacy in mammalian models of PD requires the use of gr-amounts of the compound. However, not enough compound is on sale, and no synthetic route has been reported until now, which hampers the molecule progress towards clinical trials. To circumvent those problems, we describe here an efficient and economical route that enables the synthesis of SynuClean-D with good yields as well as the synthesis of SynuClean-D derivatives. Structure-activity comparison of the new compounds with SynuClean-D reveals the functional groups of the molecule that can be disposed of without activity loss and those that are crucial to interfere with a-synuclein aggregation. Several of the derivatives obtained retain the parent''s compound excellent in vitro anti-aggregative activity, without compromising its low toxicity. Computational predictions and preliminary testing indicate that the blood brain barrier (BBB) permeability of SynuClean-D is low. Importantly, several of the newly designed and obtained active derivatives are predicted to display good BBB permeability. The synthetic route developed here will facilitate their synthesis for BBB permeability determination and for efficacy testing in mammalian models of PD. © 2021 The Author

Phthalates, organotin compounds and per-polyfluoroalkyl substances in semiconfined areas of the Spanish coast: occurrence, sources and risk assessment

Postprint3,25

Descriptive Analysis of the Performance of a Vegetated Swale through Long-Term Hydrological Monitoring: A Case Study from Coventry, UK

Vegetated swales are a popular sustainable drainage system (SuDS) used in a wide range of environments from urban areas and transport infrastructure, to rural environments, sub-urban and natural catchments. Despite the fact that vegetated swales, also known as grassed swales, have received scientific attention over recent years, especially from a hydrological perspective, there is a need for further research in the field, with long-term monitoring. In addition, vegetated swales introduce further difficulties, such as the biological growth occurring in their surface layer, as well as the biological evolution taking place in them. New developments, such as the implementation of thermal devices within the cross-section of green SuDS for energy saving purposes, require a better understanding of the long-term performance of the surface temperature of swales. This research aims to contribute to a better understanding of these knowledge gaps through a descriptive analysis of a vegetated swale in Ryton, Coventry, UK, under a Cfb Köppen climatic classification and a mixed rural and peri-urban scenario. Precipitation and temperature patterns associated with seasonality effects were identified. Furthermore, a level of biological evolution was described due to the lack of periodical and planned maintenance activities, reporting the presence of both plant species and pollinators. Only one event of flooding was identified during the three hydrological years monitored in this research study, showing a robust performance

The Spanish Network on Environmental DMAs: introduction and main activities

Comunicación presentada en: V Reunión Española de Ciencia y Tecnología de Aerosoles – RECTA 2011 celebrada del 27 al 29 de junio de 2011 en CIEMAT, Madrid

Web Application for Atmospheric Aerosol Data Management: Software and Case Study in the Spanish Network on Environmental Differential Mobility Analysers

[Abstract] SCALA© (Sampling Campaigns for Aerosols in the Low Atmosphere) is a web-based software system that was developed in a multidisciplinary manner to integrally support the documentation and the management and analysis of atmospheric aerosol data from sampling campaigns. The software development process applied considered the prototyping and the evolutionary approaches. The software product (SCALA©) allows for the comprehensive management of the sampling campaigns’ life cycle (management of the profiles and processes involved in the start-up, development and closure of a campaign) and provides support for both intra- and inter-campaigns data analysis. The pilot deployment of SCALA© considers the Spanish Network on Environmental Differential Mobility Analysers (DMAs) (REDMAAS) and the PROACLIM project. This research project involves, among other objectives, the study of temporal and spatial variations of the atmospheric aerosol through a set of microphysical properties (size distribution, optical properties, hygroscopicity, etc.) measured in several locations in Spain. The main conclusions regarding size distribution are presented in this work. These have been have been extracted through SCALA© from the data collected in the REDMAAS 2015 and 2019 intercomparison campaigns and two years (2015 and 2016) of measurements with two Scanning Mobility Particle Sizers (SMPS) at CIEMAT (Madrid, central Spain) and UDC (A Coruña, NW of Spain) sites.Ministerio de Economía y Competitividad; CGL2014-52877-RMinisterio de Economía y Competitividad; CGL2017-85344-RXunta de Galicia; GRC2013-047Xunta de Galicia; ED431C 2017/28Gobierno Regional de Madrid; Y2018/EMT-517

Occurrence of organotin compounds in waters of the spanish coast under the European Water Framework Directive

Organotin compounds (OTCs), such as tributyltin (TBT), are persistent organic pollutants that are present in water samples (surface water, river water, sea water, waste water, etc.) because of anthropogenic activities (antifouling agents in ship paints, biocides in polymers, etc.). The toxicity and endocrine disruption potential of these chemicals have been demonstrated even at very low levels (<1 ng L−1) (Devos et al. 2012). Due to the extensive presence of OTCs in all environmental media as well as their adverse effects on human health and biota, quantitative and qualitative determination of those com-pounds in complex environmental matrices has become a matter of great concern, mainly butyl and phenyl-substituted. Also, these compounds are included in the list of priority substances according to the EU Directive 2013/39/EU amending Directives 2000/60/EC and 2008/105/EC as regards priority substances in the field of water policy. This directive specifies annual average environmental quality standard (AA-EQS) of 0.2 ng L−1 TBT and a maximum allowable environmental quality standard (MAC-EQS) of 1.5 ng L−1 TBT for all surface waters. Samples were collected in two semiconfined coastal areas, one of them an area with high industrial and port activities (Ría de Vigo) and the other one with high touristic and agricultural activity (Mar Menor).The sampling campaigns were performed in spring and autumn of 2015. The levels of MBT, DBT, TBT, MPhT, DPhT and TPhT in the seawater samples were analyzed by HS-SPME-GC–QqQMS/ MS method (Moscoso-Pérez et al. 2015). MPhT, DPhT and TPhT were not detected in any sample at levels higher than LOQ. For butylated compounds, MBT, DBT and TBT were detected in 100% of the analyzed samples in the Mar Menor. In the Vigo estuary, MBT has been detected in 83.3% of the samples, the DBT in 75% and the TBT in 88%. The TBT is present in 92% of the total of 39 analyzed samples, being detected in 100% of the samples of the Mar Menor and in 88% of the samples of the Ría de Vigo. These levels are similar than those detected in other locations, and lower than the detected in ports near the coast of Gijón characterized by a great maritime traffic (Centineo et al. 2004).Program of Consolidation and Structuring of Units of Competitive Investigation of the University System of Galicia (Xunta de Galicia) potentially cofinanced by ERDF in the frame of the operative Program of Galicia 2007-2013 (reference: GRC2013-047) and by the Ministry of Economy and Competitiveness (IMPACTA, project reference: CTM2013-48194-C3-2-R, and ARPA-ACUA, project reference: CTM2016-77945-C3-3-R)

Alchemical Design of Pharmacological Chaperones with Higher Affinity for Phenylalanine Hydroxylase

Phenylketonuria (PKU) is a rare metabolic disease caused by variations in a human gene, PAH, encoding phenylalanine hydroxylase (PAH), and the enzyme converting the essential amino acid phenylalanine into tyrosine. Many PKU-causing variations compromise the conformational stability of the encoded enzyme, decreasing or abolishing its catalytic activity, and leading to an elevated concentration of phenylalanine in the blood, which is neurotoxic. Several therapeutic approaches have been developed to treat the more severe manifestations of the disorder, but they are either not entirely effective or difficult to adhere to throughout life. In a search for novel pharmacological chaperones to treat PKU, a lead compound was discovered (compound IV) that exhibited promising in vitro and in vivo chaperoning activity on PAH. The structure of the PAH-IV complex has been reported. Here, using alchemical free energy calculations (AFEC) on the structure of the PAH-IV complex, we design a new generation of compound IV-analogues with a higher affinity for the enzyme. Seventeen novel analogues were synthesized, and thermal shift and isothermal titration calorimetry (ITC) assays were performed to experimentally evaluate their stabilizing effect and their affinity for the enzyme. Most of the new derivatives bind to PAH tighter than lead compound IV and induce a greater thermostabilization of the enzyme upon binding. Importantly, the correspondence between the calculated alchemical binding free energies and the experimentally determined ¿¿Gb values is excellent, which supports the use of AFEC to design pharmacological chaperones to treat PKU using the X-ray structure of their complexes with the target PAH enzyme. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

A pyrene-inhibitor fluorescent probe with large stokes shift for the staining of Aβ1–42, α-synuclein, and amylin amyloid fibrils as well as amyloid-containing staphylococcus aureus biofilms

Amyloid fibrils formed by a variety of peptides are biological markers of different human diseases, such as Alzheimer, Parkinson or Type II diabetes, and are structural constituents of bacterial biofilms. Novel fluorescent probes offering improved sensitivity or specificity towards that diversity of amyloid fibrils, or providing alternative spectral windows are needed to improve the detection or the identification of amyloid structures. One potential source for such new probes is offered by molecules known to interact with fibrils, such as the inhibitors of amyloid aggregation found in drug discovery projects. Here, we show the feasibility of the approach by designing, synthesizing and testing several pyrene-based fluorescent derivatives of a previously discovered inhibitor of the aggregation of the Aβ1-42 peptide. All the derivatives tested retain the interaction with the amyloid architecture and allow its staining. The more soluble derivative, compound 1D, stains similarly well amyloid fibrils formed by Aβ1-42, α-synuclein or amylin, provides a sensitivity only slightly lower than that of Thioflavin T, displays a large Stokes shift, allows an efficient excitation in the UV spectral region,and it is not cytotoxic. Compound 1D can also stain amyloid fibrils formed by Staphylococcal peptides present in biofilm matrices and can be used to distinguish, by direct staining,S. aureus biofilms containing amyloid forming phenol soluble modulins from those lacking them.IL is supported by the Spanish Ministry of Economy and Competitiveness grant BIO2014-53530-R. SVis supported by grant BIO2016-783-78310-R and by ICREA (ICREA Academia 2015). MDD is supported by the Government of Aragon (GA E-102). JS is supported by grants BFU2016-78232-P (MINECO, Spain) and E45_17R (Gobierno de Aragón, Spain). JS and IL acknowledge financial support from grant CI-2017/001-3 (Campus Iberus, Spain). AM was a recipient of a predoctoral FPU fellowship from the Spanish Government

Tracers and impact of open burning of rice straw residues on PM in Eastern Spain

6 figures, 3 tables.-- © 2007. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/Biomass burning emissions of rice straw residues may be carried out near urban agglomerations and may present a potential health risk for the population. Thus, tracers of these emissions should be clearly identified. We present a detailed chemical characterisation, including inorganic and organic tracer species, of PM10 aerosol at a rural site located close to the urban agglomeration of Valencia (Eastern Spain) during the rice straw burning season in 2006. Our results show that open burning of rice field residues increased daily PM10 concentrations on a regional scale (approximately 17,400 ha) by 10-15 μg m-3 on average, with a maximum of 30 μg m-3 on peak episodic days. PM10 levels during open burning events were especially enriched in oxalate, fluoranthene, C31 n-alkane, levoglucosan, K, water-soluble organic carbon (WSOC), oleic acid, Cl-, Na, NO3 -, and V. High enrichments were also obtained for Zn, Pb, Cr, Cd, and Na, probably as a consequence of the bioaccumulation of trace metals in rice straw and the influence of sea spray and brackish waters on the crops. Anthropogenic contributions from lubricant oil residues, probably from agricultural machinery or nearby traffic emissions, were also detected in the levels of n-alkanes (C19). The high Carbon Preference Index (CPI; >3.5) obtained for n-alkanoic acids confirmed their mostly biogenic origin. Organic tracers were more sensitive than inorganic species to the influence of indirect (regional scale or long-range transported) biomass burning emissions. Source apportionment of the PM10 mass by means of PCA-MLRA showed that rice straw burning reached maximum contributions up to 40% of the PM10 mass during peak episodes.Meteorological data were collected from the flux tower located at the rice fields from CARBOEUROPE IP EU project. The sampling equipment and the site were provided by the DEVESA-ALBUFERA department (Valencia City Council) in the framework of their participation in the ECORICE LIFE project. [...]. The work at Ghent University was supported by the Belgian Federal Science Policy Office and the Research Foundation—Flanders (FWO)