Insulin in Central Nervous System: More than Just a Peripheral Hormone

Insulin signaling in central nervous system (CNS) has emerged as a novel field of research since decreased brain insulin levels and/or signaling were associated to impaired learning, memory, and age-related neurodegenerative diseases. Thus, besides its well-known role in longevity, insulin may constitute a promising therapy against diabetes- and age-related neurodegenerative disorders. More interestingly, insulin has been also faced as the potential missing link between diabetes and aging in CNS, with Alzheimer's disease (AD) considered as the “brain-type diabetes.” In fact, brain insulin has been shown to regulate both peripheral and central glucose metabolism, neurotransmission, learning, and memory and to be neuroprotective. And a future challenge will be to unravel the complex interactions between aging and diabetes, which, we believe, will allow the development of efficient preventive and therapeutic strategies to overcome age-related diseases and to prolong human “healthy” longevity. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: diabetes and AD, both in terms of intracellular signaling and potential therapeutic approach

A hybrid approach to operational planning in home health care

Home health care (HHC) management needs to plan their operations to synchronize professionals and allocate resources to perform several HHC services needed by patients. The growing demand for this type of service dictates the interest of all the stakeholders (professionalsand patients) in finding high-quality daily solutions and logistics. Routing and scheduling are problems of combinatorial nature, extremely complex, and require sophisticated optimization approaches. This work aims to contribute to cost-efficient decision-making in the general improvement of the service quality. Thus, a mixed integer linear programming model, a genetic algorithm, and a hybrid approach were used to solve the operational planning through test instances of different sizes for public home care providers. Computational results are presented, followed by a discussion on the advantages and shortcomings, highlighting the strength of each approach.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES (PIDDAC) to CeDRI (UIDB/05757/2020 and UIDP/05757/2020), SusTEC (LA/P/0007/2021) and ALGORITMI Center (UIDB/00319/2020). Filipe Alves thanks the Foundation for Science and Technology (FCT, Portugal) for supporting its research with the PhD grant SFRH/BD/143745/2019.info:eu-repo/semantics/publishedVersio

Development of new vocational training modules on sustainable buildings maintenance and refurbishment

This article presents the methodology and main results obtained in Spain within the FORMAR project, a European-funded project under the Leonardo Da Vinci scheme (Lifelong Learning Programme), whose main goal is to jointly develop training resources and modules to improve the skills on sustainability issues of buildings maintenance and refurbishment workers, in three different European countries: Spain, Portugal (Project Coordinator) and France. The Units of Short-term Training (UST) developed within this project are focused on the VET of carpenters, painters, bricklayers, building technicians and installers of solar panels, and a transversal unit containing basic concepts on sustainable construction and nearly Zero Energy Buildings (n-ZEB) is also developed. In parallel, clients’ guides for the aforementioned professionals are also implemented to improve the information provided to clients and owners in order to support the procurement decisions regarding building products and materials. Therefore, the project provides an opportunity to exchange experiences between organizations of these three European countries, as the UST will be developed simultaneously in each of them, exploring opportunities for training, guidance and exchange of experience. Even though the UST will have a common structure and contents, they will be slightly different in each country to adapt them to the different specific training needs and regulations of Spain, Portugal and France. This paper details, as a case study, the development process of the UST for carpenters and building technicians in Spain, including the analysis of needs and existing training materials, the main contents developed and the evaluation and testing process of the UST, which involves the active participation of several stakeholders of this sector as well as a classroom testing to obtain the students’ feedback

Three dimensional printing : A new approach for the manufacture of individualized medicines

Poster presented at the FIP Virtual Event, 4-25 September 2020N/

Species gap analysis in DNA barcode reference libraries of marine non-indigenous species in the Azores archipelago

Coastal regions are widely recognised for their ecologic and socio-economic importance. The spread of invasive species, along with global climate change, overexploitation, pollution and habitat destruction, is a major threat to coastal ecosystems (Solan et al. 2004). Some of these species, in particular macroalgae and invertebrates, can spread quickly and become invasive, causing severe ecologic and economic impacts. When prevention fails, the early detection and surveillance of NIS could be essential for coordinating a timely and effective response to invasions. Marine ecosystems on oceanic islands, such as Azores, can be especially prone to invasions by non-indigenous species since they are characterized by a small number of native species and by a high availability of empty niches, and thus, the list of NIS is relatively long (Micael et al. 2014). There are no doubts that traditional morphology-based methods have highly contributed to the current knowledge about NIS communities inhabiting Portuguese coastal waters, including the Portuguese oceanic islands (Micael et al. 2014, Chainho et al. 2015). However, the hurdles associated with morphological methods may compromise the early detection and monitoring of the most risky species. On the other hand, DNA-based tools promise advantages over traditional ones, particularly the identification of individuals and life stages that cannot be recognized by using morphological approaches (Darling and Mahon 2011). Plus, most surveys typically target specific species or taxonomic groups, which may neither accurately represent overall ecosystems’ condition nor allow an early detection of NIS. Due to the above-mentioned reasons, it becomes a priority to develop and optimize novel detection methods capable to overcome some of these challenges and that would allow an early detection and ease the monitoring of NIS in coastal ecosystems. Particularly, the combination of DNA barcoding with high-throughput sequencing (HTS) renders metabarcoding the capacity to bolster current biodiversity assessments techniques (Cristescu 2014). Within this approach, genetic information can be obtained through the use of standardized DNA barcode markers targeting a wide taxonomic range of organisms in mixed specimens or environmental samples (Cristescu 2014). DNA-based tools promise a number of potential benefits over traditional methods, including increased sensitivity and specificity as well as greater throughput and cost effectiveness. However, the success of DNA-based methods is greatly dependent on the availability, taxonomic coverage and reliability of reference sequence databases, whose deficiencies can potentially compromise species identifications through HTS (Briski et al. 2016). In this study we conducted a species-gap analysis of DNA barcode sequences available for marine NIS occurring in the Azores archipelago in the Barcode of Life Data System V4 (BOLD V4) (Ratnasingham and Hebert 2007) and in the GenBank (https://www.ncbi.nlm.nih.gov/genbank/). The list of NIS occurring in Azores was compiled from a wide variety of sources, mainly from literature searches through scientific papers and reports, including recent field and taxonomic studies, and supplemented with existing databases and this is the list that was submitted to the 2019 interim ICES WGITMO report (International Council for the Exploration of the Sea; Working Group on Introductions and Transfers of Marine Organisms). The taxonomic classification of the compiled NIS followed the AlgaeBase and World Register of Marine Species (WoRMS) databases. A checklist of 80 marine NIS occurring in Azores archipelago was compiled and the species in the list were checked for the presence of public sequences on both BOLD v4 and GenBank databases. The species in the list were distributed by three kingdoms: i) Animalia (48 species), ii) Plantae (30 species) and iii) Chromista (2 species), comprehending 10 phyla. The most well represented phyla with NIS were Chordata (15 species), Mollusca and Bryozoa (both with 8 species) within Animalia, and Rhodophyta within Plantae (26 species); while the only represented phyla within Chromista was Ochrophyta with 2 species. In total, 3,884 sequences belonging to 25 different markers were found for the 80 species, published in BOLD and GenBank. Among these published sequences, the COI-5P is the most well represented loci, with 3,224 records belonging to 44 species. However, from the total species in the list, 25 were still missing a DNA sequence, which corresponded to ca. 31% of the total NIS. In addition, within sequenced species ca. 14% were singletons (i.e. only one sequence available). Animalia NIS were the most well represented with sequences, missing only for ca. 27% of the species, while for Chromista and Plantae the gap of missing species was higher than 35%. The current study allowed us to characterize the gaps in available sequences in public repositories for marine NIS occurring in the Azores archipelago. Actions developing DNA-based tools should be a priority for detection and effective management of biological invasions. DNA-based tools would allow the detection of early developmental stages or smaller organisms, reducing the time from introduction to discovery and increasing the success of NIS control and/or eradication (Holman et al. 2018). However, the gaps found in reference libraries can have strong implications for an accurate species identification through DNA-based tools. Prioritization efforts should be conducted in order to fulfil these gapsFCT – Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project PTDC/BIA-BMA/29754/2017 and by FEDER funds through the Operational Programme for Competitiveness Factors - COMPETE and by National Funds through FCT - Foundation for Science and Technology under the UID/BIA/50027/2013 and POCI-01-0145-FEDER-00682

Insulin restores metabolic function in cultured cortical neurons subjected to oxidative stress

We previously demonstrated that insulin has a neuroprotective role against oxidative stress, a deleterious condition associated with diabetes, ischemia, and age-related neurodegenerative diseases. In this study, we investigated the effect of insulin on neuronal glucose uptake and metabolism after oxidative stress in rat primary cortical neurons. On oxidative stress, insulin stimulates neuronal glucose uptake and subsequent metabolism into pyruvate, restoring intracellular ATP and phosphocreatine. Insulin also increases intracellular and decreases extracellular adenosine, counteracting the effect of oxidative stress. Insulin effects are apparently mediated by phosphatidylinositol 3-K and extracellular signal-regulated kinase signaling pathways. Extracellular adenosine under oxidative stress is largely inhibited after blockade of ecto-5'-nucleotidase, suggesting that extracellular adenosine results preferentially from ATP release and catabolism. Moreover, insulin appears to interfere with the ATP release induced by oxidative stress, regulating extracellular adenosine levels. In conclusion, insulin neuroprotection against oxidative stress-mediated damage involves 1) stimulation of glucose uptake and metabolism, increasing energy levels and intracellular adenosine and, ultimately, uric acid formation and 2) a decrease in extracellular adenosine, which may reduce the facilitatory activity of adenosine receptor

FTIR spectroscopic and theoretical study of matrix-isolated (E)-1-(cyclopropyldiazenyl)naphthalen-2-ol

Photochromic systems are important due to their industrial applications in variable optical transmission materials and optobioelectronic devices. For such applications, the organic photochromic compounds involved are usually incorporated in polymers, liquid crystalline materials, or other convenient host matrices [1, 2]. Herein, a photochromic compound, (E)-1-(cyclopropyldiazenyl)naphthalen-2-ol (show in Figure 1), which was synthesized by a published method [3] and characterized, was isolated in a cryogenic argon matrix and its structure as well as UV-induced phototransformations were characterized by IR spectroscopy. The structures of the starting compound and of the generated photoproducts were identified by comparison of their experimental IR spectra with the spectra theoretically calculated at the DFT (B3LYP)/6-311++G(d,p) level for several possible tautomeric and rotameric forms.Fundação para a Ciência e a Tecnologia (FCT

Effect of the matrix system in delivery and in vitro bioactivity of microencapsulated Oregano essential oil

Available at ScienceDirectThe effect of encapsulating matrix on retention, protection and delivery of Oregano essential oil (EO) was studied. EO was encapsulated in rice starch porous spheres, inulin and gelatine/sucrose capsules by spray drying. Gelatine/sucrose matrix was also dried by freeze drying. Experimental designs were applied to test the effect of bonding agents and solids content for rice starch and drying temperature and solids content for inulin and gelatine/sucrose systems. The ratio of gelatine/sucrose was also tested. EO was identified (confocal laser scanning microscopy and FT-IR) in all tested matrices and the release profiles, antioxidant activity and antimicrobial activity of encapsulates evaluated. Results showed that the three tested materials are able to encapsulate Oregano EO. Higher diffusion coefficients were obtained for starch microcapsules (about 10 13 m2/s) followed by spray-dried gelatine/sucrose systems (about 10 15 m2/s) and inulin microcapsules (about 10 16 m2/s). Gelatine/sucrose microparticles exhibit high antioxidant and antimicrobial activity while inulin and rice starch microencapsulates ensure higher stabilit

The interplay between redox signalling and proteostasis in neurodegeneration: In vivo effects of a mitochondria-targeted antioxidant in Huntington's disease mice.

Abnormal protein homeostasis (proteostasis), dysfunctional mitochondria, and aberrant redox signalling are often associated in neurodegenerative disorders, such as Huntington's (HD), Alzheimer's and Parkinson's diseases. It remains incompletely understood, however, how changes in redox signalling affect proteostasis mechanisms, including protein degradation pathways and unfolded protein responses (UPR). Here we address this open question by investigating the interplay between redox signalling and proteostasis in a mouse model of HD, and by examining the in vivo effects of the mitochondria-targeted antioxidant MitoQ. We performed behavioural tests in wild-type and R6/2 HD mice, examined markers of oxidative stress, UPR activation, and the status of key protein degradation pathways in brain and peripheral tissues. We show that R6/2 mice present widespread markers of oxidative stress, with tissue-specific changes in proteostasis that were more pronounced in the brain and muscle than in the liver. R6/2 mice presented increased levels of cytosolic and mitochondrial chaperones, particularly in muscle, indicating UPR activation. Treatment with MitoQ significantly ameliorated fine motor control of R6/2 mice, and reduced markers of oxidative damage in muscle. Additionally, MitoQ attenuated overactive autophagy induction in the R6/2 muscle, which has been associated with muscle wasting. Treatment with MitoQ did not alter autophagy markers in the brain, in agreement with its low brain bioavailability, which limits the risk of impairing neuronal protein clearance mechanisms. This study supports the hypotheses that abnormal redox signalling in muscle contributes to altered proteostasis and motor impairment in HD, and that redox interventions can improve muscle performance, highlighting the importance of peripheral therapeutics in HD

Histone Deacetylase Inhibitors Protect Against Pyruvate Dehydrogenase Dysfunction in Huntington's Disease

Transcriptional deregulation and changes in mitochondrial bioenergetics, including pyruvate dehydrogenase (PDH) dysfunction, have been described in Huntington's disease (HD). We showed previously that the histone deacetylase inhibitors (HDACIs) trichostatin A and sodium butyrate (SB) ameliorate mitochondrial function in cells expressing mutant huntingtin. In this work, we investigated the effect of HDACIs on the regulation of PDH activity in striatal cells derived from HD knock-in mice and YAC128 mice. Mutant cells exhibited decreased PDH activity and increased PDH E1alpha phosphorylation/inactivation, accompanied by enhanced protein levels of PDH kinases 1 and 3 (PDK1 and PDK3). Exposure to dichloroacetate, an inhibitor of PDKs, increased mitochondrial respiration and decreased production of reactive oxygen species in mutant cells, emphasizing PDH as an interesting therapeutic target in HD. Treatment with SB and sodium phenylbutyrate, another HDACI, recovered cell viability and overall mitochondrial metabolism in mutant cells. Exposure to SB also suppressed hypoxia-inducible factor-1 (HIF-1α) stabilization and decreased the transcription of the two most abundant PDK isoforms, PDK2 and PDK3, culminating in increased PDH activation in mutant cells. Concordantly, PDK3 knockdown improved mitochondrial function, emphasizing the role of PDK3 inactivation on the positive effects achieved by SB treatment. YAC128 mouse brain presented higher mRNA levels of PDK1-3 and PDH phosphorylation and decreased energy levels that were significantly ameliorated after SB treatment. Furthermore, enhanced motor learning and coordination were observed in SB-treated YAC128 mice. These results suggest that HDACIs, particularly SB, promote the activity of PDH in the HD brain, helping to counteract HD-related deficits in mitochondrial bioenergetics and motor function.SIGNIFICANCE STATEMENT The present work provides a better understanding of mitochondrial dysfunction in Huntington's disease (HD) by showing that the pyruvate dehydrogenase (PDH) complex is a promising therapeutic target. In particular, the histone deacetylase inhibitor sodium butyrate (SB) may indirectly (through reduced hypoxia-inducible factor 1 alpha stabilization) decrease the expression of the most abundant PDH kinase isoforms (e.g., PDK3), ameliorating PDH activity and mitochondrial metabolism and further affecting motor behavior in HD mice, thus constituting a promising agent for HD neuroprotective treatment.FCT, Santa Casa da Misericórdia de Lisboa (SCML), Fundação Luso-Americana para o Desenvolvimento (FLAD) Life Scienc