Neospora caninum: high susceptibility to the parasite in C57BL/10ScCr mice

Neospora caninum: high susceptibility to the parasite in C57BL/10ScCr miceC57BL/10ScCr mice, lack Toll-like receptor 4 and a functional Interleukin-12 receptor. Taking this into account, susceptibility of these mice to Neospora caninum infection was assessed comparatively to that of immunocompetent C57BL/10ScSn mice. C57BL/10ScCr mice inoculated intraperitoneally with 5 x 10(5) N. caninum tachyzoites showed a high Susceptibility to this parasite. All infected C57BL/10ScCr mice were dead by day 8 post-infection whereas all control C57BL/10ScSn mice survived this parasitic challenge. Immunohistochemical analysis of infected C57BL/10ScCr mice showed N. caninum tachyzoites spread in the pancreas, liver, lung, intestine, heart and brain whereas no parasites were detected in similarly infected C57BL/10ScSn controls. The higher susceptibility of C57BL/10ScCr mice to neosporosis correlates with reduced interferon-gamma mRNA expression and increased IL-4 mRNA expression, comparatively to C57BL/10ScSn controls, detected in the spleen after the parasitic challenge. C57BL/10ScCr mice could thus be used as a new experimental model where to study immunobiological mechanisms associated with host Susceptibility to neosporosis.info:eu-repo/semantics/publishedVersio

Determination and comparison of the chemical composition of Calendula L. species growing in Continental Portugal

11th National Meeting of Organic Chemistry and 4th Meeting of Therapeutic Chemistry.The flora of Continental Portugal includes three species of Calendula L. (Calendula officinalis L., C. arvensis L., C. suffruticosa Vahl), one of which comprises three subspecies (C. suffruticosa subsp. algarbiensis (Boiss.) Nyman, C. suffruticosa subsp. lusitanica (Boiss.) Ohle and C. suffruticosa subsp. cinerea (Ohle) P.Silveira & A.C.Gonç.). C. officinalis is recognised for its medical properties and its chemical composition has been widely studied (Muley, B. P., et al. J. Pharm. Res. 2009, 8, 455; Safdar, W., et al. Int. J. Cell Mol. Biol. 2010, 1, 108). Nevertheless, little is known about the chemical composition of C. arvensis and even less regarding the different subspecies of C. suffruticosa. Therefore, the present study aims the elucidation of these plants’ chemical composition and to compare and identify differences and/or similarities among them. […].Instituto da Conservação da Natureza e das Florestas; Universidade de Aveiro; FCT / MEC (FCT UID / QUI / 00062/2013); UEM CESAM (UID / AMB / 50017); FEDER (Acordo de Parceria PT2020).info:eu-repo/semantics/publishedVersio

An insight into the synthesis of cationic porphyrin-imidazole derivatives and their photodynamic inactivation efficiency against Escherichia coli

New porphyrin-imidazole derivatives were synthesised by Radziszewski reaction between 2-formyl-5,10,15,20-tetraphenylporphyrin 1 and several (hetem)aromatic 1,2-diones, which after cationization afforded promising monocationic photosensitizers 3a-d. Singlet oxygen studies have demonstrated that all the cationic porphyrin-imidazole conjugates 3a-d were capable to produce cytotoxic species. These photosensitizers were able to photoinactivate Eschericha coli and their inactivation profile was improved in the presence of KI.The authors are grateful to University of Aveiro and FCT/MCT for the financial support for QOPNA research Unit (FCT UID/QUI/00062/2019), the LAQV-REQUIMTE (UIDB/50006/2020), CESAM (UID/AMB/50017/2019) and CQUM (QUI/UI0686/2018) through national founds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement, and to the Portuguese NMR Network. The research contract of N.M.M. Moura (REF.-048-88-ARH/2018) is funded by national funds (OE), through FCT - Fundacao para a Ciencia e a Tecnologia, I.P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19

An insight on the role of photosensitizer nanocarriers for Photodynamic Therapy

Photodynamic therapy (PDT) is a modality of cancer treatment in which tumor cells are destroyed by reactive oxygen species (ROS) produced by photosensitizers following its activation with visible or near infrared light. The PDT success is dependent on different factors namely on the efficiency of the photosensitizer deliver and targeting ability. In this review a special attention will be given to the role of some drug delivery systems to improve the efficiency of tetrapyrrolic photosensitizers to this type of treatment.publishe

Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay

We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC‐2017‐CoG‐771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA‐MIC/6982/2020 (to HV); PTDC/BIA‐PLA/3432/2012 (to SRF); FCT through MOSTMICRO‐ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and FCT fellowship SFRH/BD/147052/2019 (to BMS); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie grant agreement No 839596 (to SS) and by the European Molecular Biology Organization through award ALTF 673‐2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com .A computer-aided drug design (CADD) approach was developed for a focused chemical library comprising a series of sixteen thiazolo[5,4-c]isoquinoline derivatives. Little is known about this group of heteroaromatic compounds, both from the point of view of their synthesis and their biological properties. First, our CADD approach included target prediction by Mondrian conformal prediction with the ChEMBL database. The acetylcholinesterase (AChE) was identified as having a high probability of thiazolo[5,4-c]isoquinolines being active against it. Secondly, the molecular docking predictions revealed four promising thiazoloisoquinolines (2, 7, 13 and 14) according to their prominent ligand-protein energy scores and relevant binding affinities with the AChE pocket residues. The subsequent in vitro evaluation of promising hits and related ones revealed a set of novel AChE inhibitors. Therefore, the findings reported herein may provide a new strategy for discovering novel AChE inhibitors.publishersversionpublishe

Hadron beam test of a scintillating fibre tracker system for elastic scattering and luminosity measurement in ATLAS

A scintillating fibre tracker is proposed to measure elastic proton scattering at very small angles in the ATLAS experiment at CERN. The tracker will be located in so-called Roman Pot units at a distance of 240 m on each side of the ATLAS interaction point. An initial validation of the design choices was achieved in a beam test at DESY in a relatively low energy electron beam and using slow off-the-shelf electronics. Here we report on the results from a second beam test experiment carried out at CERN, where new detector prototypes were tested in a high energy hadron beam, using the first version of the custom designed front-end electronics. The results show an adequate tracking performance under conditions which are similar to the situation at the LHC. In addition, the alignment method using so-called overlap detectors was studied and shown to have the expected precision.Comment: 12 pages, 8 figures. Submitted to Journal of Instrumentation (JINST

Starch-based films doped with porphyrinoid photosensitizers for active skin wound healing

Starch is a biodegradable and biocompatible carbohydrate that, when combined with bioactive molecules, can be processed as biomimetic platforms with enhanced performance, allowing its use as active wound dressing materials. Porphyrinoid photosensitizers can tune the physicochemical/functional profile of biomacromolecules, allowing their use in anti-infective strategies. In this work, the feasibility of using the cationic 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetraiodide (TMPyP) to enhance the physicochemical, mechanical, antimicrobial performance, and wound healing ability of casted starch-based films was studied. TMPyP conferred a reddish coloration to the films, maintaining their pristine transparency. It increased by 87 % the films hydrophobicity and, depending on the TMPyP used, conferred mobility to the starch polymeric chains. Starch/TMPyP-based films effectively photoinactivated Escherichia coli (>99.99 %) and favored the wound healing process, even in the absence of light. Therefore, the incorporation of TMPyP into starch-based formulations revealed to be a promising strategy to tune the films compaction degree while giving rise to water tolerant and photosensitive biomaterials that can act as multitarget antimicrobial medical dressings and glycocarriers of active compounds relevant for effective skin wound healing.The authors thank to University of Aveiro and FCT/MCT for the financial support provided to CICECO (UIDB/50011/2020, UIDP/50011/2020, LA/P/0006/2020), LAQV-REQUIMTE (UIDB/50006/2020 and UIDP/50006/2020), CESAM (UIDP/50017/2020, UIDB/50017/2020, LA/P/0094/2020), CEB (UIDB/04469/2020), LABBELS (LA/P/0029/2020), and to projects PORP2PS (EXPL/QUI-QOR/0586/2021) and PREVINE (FCT-PTDC/ASP-PES/29576/2017), through national funds (OE) and where applicable co-financed by the FEDER - Operational Thematic Program for Competitiveness and Internationalization - COMPETE 2020, within the PT2020 Partnership Agreement. Thanks are also due to the Portuguese NMR and Mass Networks. FCT also funded ASMJ PhD grant (2021.06854.BD), Investigator FCT program (PF, IF/00300/2015), and the Scientific Employment Stimulus program (IG, CEECIND/00430/2017; AR, 2021.02803.CEECIND). NMMM thanks FCT for funding through program DL 57/2016 (CDL-CTTRI-048-88-ARH/2018). The authors also acknowledge to POTATOPLASTIC project (POCI-01-0247-FEDER-017938), financed by FEDER through POCI, to Isolago – Indústria de Plásticos, S. A., the project leader, and to A Saloinha, Lda. company for providing the starch-rich potato washing slurries.info:eu-repo/semantics/publishedVersio

Cognitive appraisal of environmental stimuli induces emotion-like states in fish

The occurrence of emotions in non-human animals has been the focus of debate over the years. Recently, an interest in expanding this debate to non-tetrapod vertebrates and to invertebrates has emerged. Within vertebrates, the study of emotion in teleosts is particularly interesting since they represent a divergent evolutionary radiation from that of tetrapods, and thus they provide an insight into the evolution of the biological mechanisms of emotion. We report that Sea Bream exposed to stimuli that vary according to valence (positive, negative) and salience (predictable, unpredictable) exhibit different behavioural, physiological and neuromolecular states. Since according to the dimensional theory of emotion valence and salience define a two-dimensional affective space, our data can be interpreted as evidence for the occurrence of distinctive affective states in fish corresponding to each the four quadrants of the core affective space. Moreover, the fact that the same stimuli presented in a predictable vs. unpredictable way elicited different behavioural, physiological and neuromolecular states, suggests that stimulus appraisal by the individual, rather than an intrinsic characteristic of the stimulus, has triggered the observed responses. Therefore, our data supports the occurrence of emotion-like states in fish that are regulated by the individual's perception of environmental stimuli.European Commission [265957 Copewell]; Fundacao para a Ciencia e Tecnologia [SFRH/BD/80029/2011, SFRH/BPD/72952/2010]info:eu-repo/semantics/publishedVersio

Genome variations: Effects on the robustness of neuroevolved control for swarm robotics systems

Manual design of self-organized behavioral control for swarms of robots is a complex task. Neuroevolution has proved a viable alternative given its capacity to automatically synthesize controllers. In this paper, we introduce the concept of Genome Variations (GV) in the neuroevolution of behavioral control for robotic swarms. In an evolutionary setup with GV, a slight mutation is applied to the evolving neural network parameters before they are copied to the robots in a swarm. The genome variation is individual to each robot, thereby generating a slightly heterogeneous swarm. GV represents a novel approach to the evolution of robust behaviors, expected to generate more stable and robust individual controllers, and bene t swarm behaviors that can deal with small heterogeneities in the behavior of other members in the swarm. We conduct experiments using an aggregation task, and compare the evolved solutions to solutions evolved under ideal, noise-free conditions, and to solutions evolved with traditional sensor noise.info:eu-repo/semantics/acceptedVersio

New nitroindazole-porphyrin conjugates: synthesis, characterization and antibacterial properties

The synthesis of new porphyrin-indazole hybrids by a Knoevenagel condensation of 2-formyl-5,10,15,20-tetraphenylporphyrin and N-methyl-nitroindazolylacetonitrile derivatives is reported. The target compounds were isolated in moderate to good yields (32-57%) and some of the isolated porphyrin-indazole conjugates showed good performance in the generation of singlet oxygen when irradiated with visible light. Their efficiency as photosensitizers in the photoinactivation of methicillin resistant Staphylococcus aureus-MRSA was evaluated. All derivatives showed to be able to photoinactivate the MRSA bacteria. Compound 3a appears to be the most promising photosensitiser (PS) in the photoinactivation of these bacteria, despite being the least efficient in singlet oxygen generation. The addition of potassium iodide (KI) significantly potentiated the antimicrobial Photodynamic Therapy (aPDT) process mediated by all the analysed porphyrin-indazole conjugates. The combined action of nitroindazole-porphyrins with potassium iodide (KI) action appears to be promising in the photoinactivation of MRSA.publishe