Editorial

UID/PAM/00417/2019 DL 57/2016/CP1453/CT0033publishersversionpublishe

Machine learning-enhanced T cell neoepitope discovery for immunotherapy design

Immune responses mediated by T cells are aimed at specific peptides, designated T cell epitopes, that are recognized when bound to human leukocyte antigen (HLA) molecules. The HLA genes are remarkably polymorphic in the human population allowing a broad and fine-tuned capacity to bind a wide array of peptide sequences. Polymorphisms might generate neoepitopes by impacting the HLA-peptide interaction and potentially alter the level and type of generated T cell responses. Multiple algorithms and tools based on machine learning (ML) have been implemented and are able to predict HLA-peptide binding affinity with considerable accuracy. Challenges in this field include the availability of adequate epitope datasets for training and benchmarking and the development of fully integrated pipelines going from next-generation sequencing to neoepitope prediction and quality analysis metrics. Effectively predicting neoepitopes from in silico data is a demanding task that has been facilitated by ML and will be of great value for the future of personalized immunotherapies against cancer and other diseases.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research received funding from Fundação para a Ciência e a Tecnologia (FCT) contract IF/00474/2014; PhD scholarship SFRH/BD/132797/2017.info:eu-repo/semantics/publishedVersio

The nucleolar protein Viriato/Nol12 is required for the growth and differentiation progression activities of the Dpp pathway during Drosophila eye development

Drosophila Decapentaplegic (Dpp), a member of the BMP2/4 class of the TGF-βs, is required for organ growth, patterning and differentiation. However, much remains to be understood about the mechanisms acting downstream of these multiple roles. Here we investigate this issue during the development of the Drosophila eye. We have previously identified viriato (vito) as a dMyc-target gene encoding a nucleolar protein that is required for proper tissue growth in the developing eye. By carrying out a targeted in vivo double-RNAi screen to identify genes and pathways functioning with Vito during eye development, we found a strong genetic interaction between vito and members of the Dpp signaling pathway including the TGF-β receptors tkv (type I), put (type II), and the co-Smad medea (med). Analyzing the expression of the Dpp receptor Tkv and the activation pattern of the pathway’s transducer, p-Mad, we found that vito is required for a correct signal transduction in Dpp-receiving cells. Overall, we validate the use of double RNAi to find specific genetic interactions and, in particular, we uncover a link between the Dpp pathway and Vito, a nucleolar component. vito would act genetically downstream of Dpp, playing an important role in maintaining a sufficient level of Dpp activity for the promotion of eye disc growth and regulation of photoreceptor differentiation in eye development

exploring knowledge, risk perception, and sexual behaviors

High circular mobility creates vulnerability and elevates risk for sexually transmitted infections (STIs) including Human Immunodeficiency Virus (HIV). We aim to explore knowledge, perceptions of risk, and sexual behaviors in relation to STIs/HIV, in Mozambican women involved in an informal cross border trade (ICBT) and residing in South Mozambique. A cross-sectional quantitative study, in 200 women cross border traders (WICBT), affiliated to the Mukhero Association, using a structured, face-to-face questionnaire, was conducted. Descriptive statistics and Pearson’s Chi-square test were used. The median age of participants was 37.0 years (interquartile range (IQR): 31.0–43.0), 100% were literate, travelled on average six times a month. WICBT with a high education level were more likely to have awareness of Gonorrhea, Syphilis, and Candidiasis; to self-perceive being at risk of getting HIV, Syphilis, and Human Papilloma Virus (HPV); and to test for HIV and Syphilis. Those with a low education level were more likely to have misconceptions about HIV and ever have sex in exchange for money/goods/services. Married participants were more likely to know how to prevent HIV. Participants with a high income were more likely to know about HPV; to self-perceive being at risk of getting Syphilis; to point sex workers as being at higher risk of getting HPV; and to ever test for HIV. WICBT with a low income were more likely to have sex in exchange for money/goods/services. Low and inconsistent knowledge and misconceptions of STIs/HIV, high sexual risky behavior, low perception of risk of getting STIs/HIV among this neglected and key population suggests their increased vulnerability to the STIs/HIV.publishersversionpublishe

HABIT - a webserver for interactive T cell neoepitope discovery

bioRxiv - the Preprint Server for Biology.Neoepitopes generated by amino acid variants specifically found in pathogens or cancer cells are gaining momentum in immunotherapy development. HABIT (HLA Binding InTelligence) is a web platform designed to generate and analyse machine learning-based T cell epitope predictions for improved neoepitope discovery. Availability and Implementation: HABIT is available at http://habit.evobiomed.com . Peptide-HLA binding predictions by NetMHCpan 4.0 and NetMHCIIpan 3.1 were implemented in a web application for interactive data exploration using shiny package powered by RStudio.info:eu-repo/semantics/publishedVersio

Assessment of the biotic effects of cephalexin on clinical strains of staphylococcus aureus and enterococcus faecalis isolated from a polymicrobial infection

info:eu-repo/semantics/publishedVersio

Seed extracts of Gleditsia triacanthos : functional properties evaluation and incorporation into galactomannan films

In this work, three different extraction procedures were performed in Gleditsia triacanthos seeds in order to obtain extracts that were characterized in terms of the yield of extraction, total phenolic content and antioxidant properties. The extracts have been shown to contain considerable amounts of phenolic compounds (between 4.93 and 12.34 mg galicacid g extract − 1) and antioxidant activity between 18.77 and 71.59%. Different concentrations of one of the extracts (extract presenting simultaneously the best values of total phenolic content, radical scavenging activity and the concentration of the compounds that caused a 50% inhibition of the radical scavenging activity) were incorporated into G. triacanthos galactomannan solutions and films were cast from these. A 2 2 full factorial design was done to evaluate the effect of the galactomannan and extract concentrations in film properties. Galactomannan concentrations ranging from 0.5 to 1.5% and extract concentrations ranging from 0 to 1.0%, were used and the evaluated film properties as: water vapour permeability, colour, total phenolic compounds content and antioxidant activity. This work has shown that G. triacanthos can be used not only as a source of galactomannan films suitable to incorporate antioxidant compounds for further application in the food industry but also as a source of the active compounds to be incorporated.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil).Fundação para a Ciência e Tecnologia (FCT) - SFRH/BD/ 23897/2005; SFRH/BD/32566/200

Bacteriophages a bio sustainable solution to tackle Alzheimer´s disease

Introduction: Amyloid-beta (AB) is a prime suspect to cause Alzheimers disease (AD), an irreversible, progressive and age-dependent neurodegenerative disorder affecting millions of people worldwide. An accumulation of AB in the brain leads to its aggregation into soluble oligomeric and fibrillar clusters, which are the culprits to impair synaptic function and memory formation in mice models. Currently, we lack diagnostic tools to detect AB oligomers (ABOs) in the brain, all the methods used provide a late diagnosis when there are already symptoms. Moreover, the existence of the blood-brain-barrier (BBB) is the major bottleneck for reaching the brain. To overcome this, bacteriophages (phages: bacterial viruses) are a solution, once they posses the capacity to cross the BBB. Aims: Hence, our main goals were the development of a solution to 1) detect ABOs in the brain and monitor AD progression and 2) delay or prevent the onset of the symptoms. Methods: We resorted to phage engineering with AB-targeting peptides described to recognize ABOs and fibrils with high affinity. These were tested for their capacity to detect ABOs in tissues samples and their effect on AB aggregation. Results: The engineered phages are able to detect the early and toxic forms of AB in brain tissue of APP/PS1 transgenic mice and human donors. Moreover, these phages also possess a high therapeutic potential by inhibiting the aggregation process of AB. Conclusion: We provide a highly versatile bio-inspired solution based on phages displaying AB peptides to detect early soluble AB oligomers in the brain, and possibly prevent, or delay, the onset of the symptoms, consequently inhibiting AD progression.The authors thank the Project EARLY - Phage towards initial amyloid-beta funded by TecMinho through the iProof initiative, in the scope of the project UI-Transfer, co-financed by COMPETE 2020, through Fundo Europeu de Desenvolvimento Regional (FEDER). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit, and by LABBELS – Associate Laboratory in Biotechnology, Bioengineering and Microelectromechanical Systems, LA/P/0029/2020, center grant UID/MULTI/04046/2020 (to BioISI), PhD fellowship SFRH/BD/101171/2014 (to J.S.C.), and by Alzheimer Nederland (H.W.K.).info:eu-repo/semantics/publishedVersio

Shelf life extension of Ricotta cheese using coatings of galactomannans from nonconventional sources incorporating nisin against Listeria monocytogenes

Shelf life extension of Ricotta cheese was evaluated at 4 °C upon the use of edible coatings made of galactomannans from Gleditsia triacanthos incorporating nisin against Listeria monocytogenes. Three different treatments were tested in cheese: samples without coating; samples with coating without nisin; and samples with coating containing 50 IU·g−1 of nisin. To test the effectiveness of the treatments against L. monocytogenes, the surface of the cheese was inoculated with a suspension of the microorganism. Microbiological and physical−chemical analyses of the cheese samples were performed during 28 days. Results showed that the cheese coated with nisin-added galactomannan film was the treatment presenting the best results in terms of microbial growth delay (p < 0.05). The addition of nisin also affects (p < 0.05) the physical and mechanical properties of the films: O2 permeability decreased from 1.84 to 1.35 × 10−12 cm3·(Pa·s·m)−1; CO2 permeability increased from 1.96 to 6.31 × 10−12 cm3·(Pa·s·m)−1; opacity increased from 3.68 to 4.59%; tensile strength ranged from 0.84 to 1.46 MPa; and elongation at break improved from 50.93 to 68.16%. These results demonstrate that novel galactomannan-based edible coatings, when combined with nisin, may provide consumer-friendly alternatives to reduce L. monocytogenes postcontamination on cheese products during storage.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil)Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/32566/2006, SFRH/BD/23897/200