Can geosites be restored? The example of the Alto Vez geosite (Peneda Mountain, Portugal)

One of the most important tasks in geoheritage management is the conservation of the geosite values, protecting them from natural or human induced degradation. In some cases, degradation still occurs even with the existence of geoconservation initiatives. Normally, the loss of geodiversity features is irreversible and protection measures are only applied in order to try to stop further damage. However, should this be imperative to all types of geosites? This question emerged with the case of the restoration of the Alto Vez geosite in the Peneda Mountain, one of the most remarkable fields of glacial erratic boulders in Portugal. Besides the erratic granite boulders, other relevant glacial features occur such as an U-shaped valley and moraines, justifying the inclusion of this site as one of the most important geosites in the Portuguese geoheritage inventory. Despite its scientific relevance, it is located just outside the contiguous Peneda-Gerês National Park, the most important protected area in Portugal. This national park was founded in 1971 and its limits were defined before the scientific discovery of these relevant glacial features. In 2012, a horseracing track was constructed in the geosite by the local village administration, with the removal of erratic boulders from their original place, affecting the natural landscape and the geosite’s integrity. After a claim made by a citizen, legal and administrative actions made by the Portuguese Institute of Nature Conservation and Forests and by the municipal authorities, have resulted in the closure of the racing track, an assessment of the degradation and definition of a strategy to reduce the damages. Under our supervision, a restoration plan was conducted in 2017. Aerial photos captured by unmanned aerial vehicles were used, together with dGPS and GIS procedures. The initial topography was restored using earthmoving machinery and the buried erratic boulders were identified and carefully relocated to their original position. A management plan of the geosite is being produced in order to protect it more efficiently through a statutory designation and to promote its tourism and educational uses. This case-study shows that a well-informed society is essential to help authorities to protect geoheritage and that a geosite restoration is possible when the main geodiversity features are not yet fully destroyed

Evaluation of a model photo-caged dehydropeptide as a stimuli-responsive supramolecular hydrogel

Short peptides capped on the N-terminus with aromatic groups are often able to form supramolecular hydrogels, via self-assembly, in aqueous media. The rheological properties of these readily tunable hydrogels resemble those of the extracellular matrix (ECM) and therefore have potential for various biological applications, such as tissue engineering, biosensors, 3D bioprinting, drug delivery systems and wound dressings. We herein report a new photo-responsive supramolecular hydrogel based on a “caged” dehydropeptide (CNB-Phe-ΔPhe-OH 2), containing a photo-cleavable carboxy-2-nitrobenzyl (CNB) group. We have characterized this hydrogel using a range of techniques. Irradiation with UV light cleaves the pendant aromatic capping group, to liberate the corresponding uncaged model dehydropeptide (H-Phe-ΔPhe-OH 3), a process which was investigated by 1H NMR and HPLC studies. Crucially, this cleavage of the capping group is accompanied by dissolution of the hydrogel (studied visually and by fluorescence spectroscopy), as the delicate balance of intramolecular interactions within the hydrogel structure is disrupted. Hydrogels which can be disassembled non-invasively with temporal and spatial control have great potential for specialized on-demand drug release systems, wound dressing materials and various topical treatments. Both 2 and 3 were found to be non-cytotoxic to the human keratinocyte cell line, HaCaT. The UV-responsive hydrogel system reported here is complementary to previously reported related UV-responsive systems, which are generally composed of peptides formed from canonical amino acids, which are susceptible to enzymatic proteolysis in vivo. This system is based on a dehydrodipeptide structure which is known to confer proteolytic resistance. We have investigated the ability of the photo-activated system to accelerate the release of the antibiotic, ciprofloxacin, as well as some other small model drug compounds. We have also conducted some initial studies towards skin-related applications. Moreover, this model system could potentially be adapted for on-demand “self-delivery”, through the uncaging of known biologically active dehydrodipeptides.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM (UID/QUI/00686/2019) and of IPC (UID/CTM/50025/2019). L.H. acknowledges funding from the FCT Investigator Programme through grant IF/00606/2014. FCT, FEDER, PORTUGAL2020 and COMPETE2020 are also acknowledged for funding under research project PTDC/QUI-QOR/29015/2017 (POCI-01-0145-FEDER-029015)

Bioinformatics Projects Supporting Life-Sciences Learning in High Schools

The interdisciplinary nature of bioinformatics makes it an ideal framework to develop activities enabling enquiry-based learning. We describe here the development and implementation of a pilot project to use bioinformatics-based research activities in high schools, called "Bioinformatics@school." It includes web-based research projects that students can pursue alone or under teacher supervision and a teacher training program. The project is organized so as to enable discussion of key results between students and teachers. After successful trials in two high schools, as measured by questionnaires, interviews, and assessment of knowledge acquisition, the project is expanding by the action of the teachers involved, who are helping us develop more content and are recruiting more teachers and schools.Instituto Gulbenkian de Ciênci

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3β-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis

[Abstract:] Sea hares of "Aplysia" genus are recognized as a source of a diverse range of metabolites. 5α,8α-Endoperoxides belong to a group of oxidized sterols commonly found in marine organisms and display several bioactivities, including antimicrobial, anti-tumor, and immunomodulatory properties. Herein we report the isolation of 5α,8α-epidioxycholest-6-en-3β-ol (EnP(5,8)) from "Aplysia depilans" Gmelin, based on bioguided fractionation and nuclear magnetic resonance (NMR) analysis, as well as the first disclosure of its anti-inflammatory properties. EnP(5,8) revealed capacity to decrease cellular nitric oxide (NO) levels in RAW 264.7 macrophages treated with lipopolysaccharide (LPS) by downregulation of the Nos2 (inducible nitric oxide synthase, iNOS) gene. Moreover, EnP(5,8) also inhibited the LPS-induced expression of cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) at the mRNA and protein levels. Mild selective inhibition of COX-2 enzyme activity was also evidenced. Our findings provide evidence of EnP(5,8) as a potential lead drug molecule for the development of new anti-inflammatory agents.Portugal.Fundação para a Ciência e Tecnologia; UID/QUI/50006/2019Portugal. Fundação para a Ciência e Tecnologia; PD/BD/113565/201

New eugenol derivatives with enhanced insecticidal activity

Eugenol, the generic name of 4-allyl-2-methoxyphenol, is the major component of clove essential oil, and has demonstrated relevant biological potential with well-known antimicrobial and antioxidant actions. New O-alkylated eugenol derivatives, bearing a propyl chain with terminals like hydrogen, hydroxyl, ester, chlorine, and carboxylic acid, were synthesized in the present work. These compounds were later subjected to epoxidation conditions to give the corresponding oxiranes. All derivatives were evaluated against their effect upon the viability of insect cell line Sf9 (Spodoptera frugiperda), demonstrating that structural changes elicit marked effects in terms of potency. In addition, the most promising molecules were evaluated for their impact in cell morphology, caspase-like activity, and potential toxicity towards human cells. Some molecules stood out in terms of toxicity towards insect cells, with morphological assessment of treated cells showing chromatin condensation and fragmentation, which are compatible with the occurrence of programmed cell death, later confirmed by evaluation of caspase-like activity. These findings point out the potential use of eugenol derivatives as semisynthetic insecticides from plant natural products.This research was funded by COMPETE 2020 program, co-financed by the FEDER and the European Union, PTDC/ASP-AGR/30154/2017 (POCI-01-0145-FEDER-030154). The authors also acknowledge the Foundation for Science and Technology (FCT; Portugal), and FEDER-COMPETE/QREN-EU for financial support to the research centers CQ/UM (UIDB/00686/2020), CF-UM-UP (UIDB/04650/2020) and REQUIMTE (UIDB/50006/2020). The NMR spectrometer Bruker Avance III 400 is part of the NationalNMRNetwork and was purchased within the framework of the National Program for Scientific Re-equipment, contract REDE/1517/RMN/2005, with funds from POCI 2010 (FEDER) and the FCT. The authors would also like to thank RIAIDT-USC for the use of their analytical facilities

Aryl-capped lysine-dehydroamino acid dipeptide supergelators as potential drug release systems

Employing amino acids and peptides as molecular building blocks provides unique opportunities for generating supramolecular hydrogels, owing to their inherent biological origin, bioactivity, biocompatibility, and biodegradability. However, they can suffer from proteolytic degradation. Short peptides (<8 amino acids) attached to an aromatic capping group are particularly attractive alternatives for minimalistic low molecular weight hydrogelators. Peptides with low critical gelation concentrations (CGCs) are especially desirable, as the low weight percentage required for gelation makes them more cost-effective and reduces toxicity. In this work, three dehydrodipeptides were studied for their self-assembly properties. The results showed that all three dehydrodipeptides can form self-standing hydrogels with very low critical gelation concentrations (0.050.20 wt%) using a pH trigger. Hydrogels of all three dehydrodipeptides were characterised by scanning tunnelling emission microscopy (STEM), rheology, fluorescence spectroscopy, and circular dichroism (CD) spectroscopy. Molecular modelling was performed to probe the structural patterns and interactions. The cytotoxicity of the new compounds was tested using human keratinocytes (HaCaT cell line). In general, the results suggest that all three compounds are non-cytotoxic, although one of the peptides shows a small impact on cell viability. In sustained release assays, the effect of the charge of the model drug compounds on the rate of cargo release from the hydrogel network was evaluated. The hydrogels provide a sustained release of methyl orange (anionic) and ciprofloxacin (neutral), while methylene blue (cationic) was retained by the network.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding of CQUM (UID/QUI/00686/2019), IPC (UIDP/CTM/05256/2020 and UIDB/05256/2020) and REQUIMTE/LAQV (UIDB/50006/2020). L.H. acknowledges grant CEECINST/00156/2018. FCT, FEDER, PORTUGAL2020 and COMPETE2020 are also acknowl edged for funding under research project PTDC/QUI-QOR/29015/2017 (POCI-01-0145-FEDER 029015). TGC thanks FCT under the scope of the strategic funding of UIDB/04469/2020 unit, and LABBELS—Associate Laboratory in Biotechnology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020.info:eu-repo/semantics/publishedVersio

inTB - a data integration platform for molecular and clinical epidemiological analysis of tuberculosis

This deposit is composed by the main article plus the supplementary materials of the publication.Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data.Instituto Gulbenkian de Ciência, Programa Nacional de Luta contra a Tuberculose, Instituto Nacional de Saúde Ricardo Jorge, Administração Regional de Saúde de Lisboa e Vale do Tejo

Contribution of municipalities on the promotion of geodiversity: the example of Geovaldevez initiative

Resumos do XI CNG 2023Summary: The geodiversity concept is slowly gaining social recognition. Municipalities can play an important role in raising the awareness of their communities and tourists about the importance of geodiversity. Arcos de Valdevez municipality in Northern Portugal has developed an initiative for the educative and touristic promotion of the local geodiversity. This initiative includes publications, geological interpretation of trails, an educative kit for teachers, a dedicated website and app, and an interpretative centre where visitors can enjoy 3D and interactive devices to visualize the municipality geodiversity

Eugenol β-amino/β-alkoxy alcohols with selective anticancer activity

Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol β-amino alcohol and β-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three β-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.This research was funded by FCT under project PTDC/ASP-AGR/30154/2017 (PO-CI-01-0145- FEDER-030154) of COMPETE 2020, co-financed by FEDER and EU. FCT-Portugal and FEDERCOMPETE/ QREN-EU also gave financial support to the research centres CQ/UM (UIDB/00686/2020) and REQUIMTE (UIDB/50006/2020). The NMR spectrometer Bruker Avance III 400 (part of the National NMR Network) was financed by FCT and FEDER. Renato B. Pereira acknowledges PRIMA Foundation (H2020- PRIMA 2018—Section 2, Project MILKQUA) and FCT (PTDC/QUI-QFI/2870/2020) for the funding

Bolaamphiphilic Bis-Dehydropeptide hydrogels as potential drug release systems

The self-assembly of nanometric structures from molecular building blocks is an effective way to make new functional materials for biological and technological applications. In this work, four symmetrical bolaamphiphiles based on dehydrodipeptides (phenylalanyldehydrophenylalanine and tyrosyldehydrophenylalanine) linked through phenyl or naphthyl linkers (terephthalic acid and 2,6-naphthalenedicarboxylic acid) were prepared, and their self-assembly properties were studied. The results showed that all compounds, with the exception of the bolaamphiphile of tyrosyldehydrophenylalanine and 2,6-naphthalene dicarboxylic acid, gave self-standing hydrogels with critical gelation concentrations of 0.3 wt % and 0.4 wt %, using a pH trigger. The self-assembly of these hydrogelators was investigated using STEM microscopy, which revealed a network of entangled fibers. According to rheology, the dehydrodipeptide bolaamphiphilic hydrogelators are viscoelastic materials with an elastic modulus G' that falls in the range of native tissue (0.37 kPa brain-4.5 kPa cartilage). In viability and proliferation studies, it was found that these compounds were non-toxic toward the human keratinocyte cell line, HaCaT. In sustained release assays, we studied the effects of the charge present on model drug compounds on the rate of cargo release from the hydrogel networks. Methylene blue (MB), methyl orange (MO), and ciprofloxacin were chosen as cationic, anionic, and overall neutral cargo, respectively. These studies have shown that the hydrogels provide a sustained release of methyl orange and ciprofloxacin, while methylene blue is retained by the hydrogel network.Portugal2020, Compete2020, FEDER. PTDC/QUI-QOR/29015/2017. UIDB/04650/2020. UIDB/50006/2020. UID/QUI/00686/2019. UID/CTM/50025/2019. SFRH/BD/144017/201