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Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) can restrict viral pathogens, but pro- and anti-viral activities have been reported for coronaviruses. Here, we show that artificial overexpression of IFITMs blocks SARS-CoV-2 infection. However, endogenous IFITM expression supports efficient infection of SARS-CoV-2 in human lung cells. Our results indicate that the SARS-CoV-2 Spike protein interacts with IFITMs and hijacks them for efficient viral infection. IFITM proteins were expressed and further induced by interferons in human lung, gut, heart and brain cells. IFITM-derived peptides and targeting antibodies inhibit SARS-CoV-2 entry and replication in human lung cells, cardiomyocytes and gut organoids. Our results show that IFITM proteins are cofactors for efficient SARS-CoV-2 infection of human cell types representing in vivo targets for viral transmission, dissemination and pathogenesis and are potential targets for therapeutic approaches. IFITM proteins can inhibit several viruses, but effects on SARS-CoV-2 infection are not well understood. Here, the authors show that endogenous IFITMs support SARS-CoV-2 infection in different in vitro models by binding spike and enhancing virus entry.

In this work, optical fiber Bragg grating sensors were used to measure water velocity and examine how it was distributed in open channels. Several types of coatings were incorporated into the design of the sensors to examine their effects on the strain that the fibers experienced as a result of the water flow. Due to their low elastic coefficient, which reduced the hysteresis, the results indicated that the aluminum- and acrylate-coated fibers had the best performance. ANSYS-CFX V2020 R2 software was used to model the strain encountered by the fibers under various flow rates to assess the performance of the FBG sensors. The calculations and actual data exhibited good convergence, demonstrating the accuracy of the FBG sensors in determining water velocity. The study illustrated the usability of the proposal in both scenarios by contrasting its application in rivers and channels.

Accurate reference data to validate burned area (BA) products are crucial to obtaining reliable accuracy metrics for such products. However, the accuracy of reference data can be affected by numerous factors; hence, we can expect some degree of deviation with respect to real ground conditions. Since reference data are usually produced by semi-automatic methods, where human-based image interpretation is an important part of the process, in this study, we analyze the impact of the interpreter on the accuracy of the reference data. Here, we compare the accuracy metrics of the FireCCI51 BA product obtained from reference datasets that were produced by different analysts over 60 sites located in tropical regions of South America. Additionally, fire severity, tree cover percentage, and canopy height were selected as explanatory sources of discrepancies between interpreters’ reference BA classifications. We found significant differences between the FireCCI51 accuracy metrics obtained with the different reference datasets. The highest accuracies (highest Dice coefficient) were obtained with the reference dataset produced by the most experienced interpreter. The results indicated that fire severity is the main source of discrepancy between interpreters. Disagreement between interpreters was more likely to occur in areas with low fire severity. We conclude that the training and experience of the interpreter play a crucial role in guaranteeing the quality of the reference data.

Theoretical approaches to dehumanization consider civility to be an attribute of human uniqueness (HU). However, studies that explore the links between civility and humanness are scarce. More precisely, the present research tests whether there is a consistent relationship between civility and HU. Method and results: The first study (N = 192; Mage = 19.91; SD = 2.70; 69% women) shows that individuals infer more HU traits in the agents of civil behaviors compared to agents of other positive behaviors that are not related to civility. The second study (N = 328; Mage = 19.69; SD = 3.65; 77% women) reveals that uncivil and immoral behaviors displayed a similar pattern of inference of HU traits; however, moral behaviors were more associated with human nature than civil behaviors. Conclusions: Overall, results confirmed that civil behaviors facilitate the inference of humanness, specifically of HU traits, and that civil and moral behaviors are not equivalent in terms of the human inferences to which they lead.

Chimeric antigen receptor (CAR)-T cell therapy is a groundbreaking immunotherapy for cancer. However, the intricate and costly manufacturing process remains a hurdle. Improving the transduction rate is a potential avenue to cut down costs and boost therapeutic efficiency. Peptide nanofibrils (PNFs) serve as one such class of transduction enhancers. PNFs bind to negatively charged virions, facilitating their active engagement by cellular protrusions, which enhances virion attachment to cells, leading to increased cellular entry and gene transfer rates. While first-generation PNFs had issues with aggregate formation and potential immunogenicity, our study utilized in silico screening to identify short, endogenous, and non-immunogenic peptides capable of enhancing transduction. This led to the discovery of an 8-mer peptide, RM-8, which forms PNFs that effectively boost T cell transduction rates by various retroviral vectors. A subsequent structure-activity relationship (SAR) analysis refined RM-8, resulting in the D4 derivative. D4 peptide is stable and assembles into smaller PNFs, avoiding large aggregate formation, and demonstrates superior transduction rates in primary T and NK cells. In essence, D4 PNFs present an economical and straightforward nanotechnological tool, ideal for refining ex vivo gene transfer in CAR-T cell production and potentially other advanced therapeutic applications.

Acknowledgments: Dany Domínguez Pérez was supported by a Ph.D. grant (SFRH/BD/80592/2011) from the Portuguese Foundation for Science and Technology (FCT—Fundação para a Ciência e a Tecnologia, Portugal). A. Campos work were supported respectively by Postdoc grants SFRH/BPD/92978/2013 and SFRH/BPD/103683/2014 from the FCT. Armando A Rodríguez was supported by an Alexander von Humboldt postdoctoral fellowship (3.2-KUB/1153731 STP and the Collaborative Research Centre 1279 funded by the German Research Foundation). We are grateful to Isabel Cunha and Daniela Almeida from CIIMAR, FCUP, University of Porto, for the help in the identification, sampling and transporting of B. verrucosa specimens. To Barbara Frazão, from Instituto Português do Mar e da Atmosfera, Lisbon, Portugal for suggestions and by providing information related the species studied. This study was funded in part by the Strategic Funding UID/Multi/04423/2013 through national funds provided by FCT and the European Regional Development Fund (ERDF) in the framework of the program PT2020, by the European Structural and Investment Funds (ESIF) through the Competitiveness and Internationalization Operational Program—COMPETE 2020 and by National Funds through the FCT under the project PTDC/AAG-GLO/6887/2014 (POCI-01-0124-FEDER-016845), and by the Structured Programs of R&D&I INNOVMAR—Innovation and Sustainability in the Management and Exploitation of Marine Resources (NORTE-01-0145-FEDER-000035, Research Line NOVELMAR) and CORAL NORTE (NORTE-01-0145-FEDER-000036), and funded by the Northern Regional Operational Program (NORTE2020) through the ERDF.

Endogenous antimicrobial peptides (AMPs) play a key role in the host defense against pathogens. AMPs attack pathogens preferentially at the site of entry to prevent invasive infection. Mycobacterium tuberculosis (Mtb) enters its host via the airways. AMPs released into the airways are therefore likely candidates to contribute to the clearance of Mtb immediately after infection. Since lysozyme is detectable in airway secretions, we evaluated its antimicrobial activity against Mtb. We demonstrate that lysozyme inhibits the growth of extracellular Mtb, including isoniazid-resistant strains. Lysozyme also inhibited the growth of non-tuberculous mycobacteria. Even though lysozyme entered Mtb-infected human macrophages and co-localized with the pathogen we did not observe antimicrobial activity. This observation was unlikely related to the large size of lysozyme (14.74 kDa) because a smaller lysozyme-derived peptide also co-localized with Mtb without affecting the viability. To evaluate whether the activity of lysozyme against extracellular Mtb could be relevant in vivo, we incubated Mtb with fractions of human serum and screened for antimicrobial activity. After several rounds of sub-fractionation, we identified a highly active fraction-component as lysozyme by mass spectrometry. In summary, our results identify lysozyme as an antimycobacterial protein that is detectable as an active compound in human serum. Our results demonstrate that the activity of AMPs against extracellular bacilli does not predict efficacy against intracellular pathogens despite co-localization within the macrophage. Ongoing experiments are designed to unravel peptide modifications that occur in the intracellular space and interfere with the deleterious activity of lysozyme in the extracellular environment.

A critical challenge faced by sustainability science is to develop strategies to cope with highly uncertain social and ecological dynamics. This article explores the use of the robust control framework toward this end. After briefly outlining the robust control framework, we apply it to the traditional Gordon-Schaefer fishery model to explore fundamental performance-robustness and robustness-vulnerability trade-offs in natural resource management. We find that the classic optimal control policy can be very sensitive to parametric uncertainty. By exploring a large class of alternative strategies, we show that there are no panaceas: even mild robustness properties are difficult to achieve, and increasing robustness to some parameters (e.g., biological parameters) results in decreased robustness with respect to others (e.g., economic parameters). On the basis of this example, we extract some broader themes for better management of resources under uncertainty and for sustainability science in general. Specifically, we focus attention on the importance of a continual learning process and the use of robust control to inform this process.

Social pain is considered a feature of humanity. The goal of this study was to confirm whether children, like adults, dehumanise out-group members attributing them less capacity to experience social pain than to in-group members. A total of 119 participants aged between 9 and 13 years responded to a questionnaire which collected information about situations that caused physical pain and situations that caused social pain. The task of the participants was to indicate to what extent they considered that two persons (a member of the in-group and a member of an out-group) would experience pain in each situation. The results indicated that there was a higher estimate of social pain suffered by in-group members. There were no significant differences in the case of situations that generated physical in the groups. The results were analysed from the dehumanisation perspective.

Marine invertebrates are a prime source of biologically active peptides due to their role in humoral immunity. These peptides typically exhibit broad-spectrum functions, including antibacterial, antifungal, anticancer, and immunomodulatory activities. In this report, we describe the identification and biological characterization of five novel bioactive peptides from the marine mollusk Pisania pusio. An extract of P. pusio was analyzed using nanoLC-ESI-MS-MS, and five peptides (PP1–5) were selected via bioinformatic screening as potential antimicrobial and anticancer peptides and subsequently validated experimentally. Among these, PP1, PP2, and PP4 were identified as cryptides derived from the proteolytic cleavage of actin, while PP3 and PP5 are novel peptides with no known protein precursors. All peptides exhibited moderate activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae with minimum inhibitory concentrations (MICs) predominantly at 100 µM. In contrast, only PP1 and PP5 were active against cancer cells, with PP1 being the most effective against A375 melanoma cells (IC50 = 17.08 µM). This experimental validation confirmed the utility of the integrated in silico/peptidomic pipeline for lead identification. None of these peptides showed significant hemolytic activity or toxicity on fetal lung fibroblasts over 800 μM, demonstrating promising in vitro selectivity. These results highlight the multifunctional nature of P. pusio-derived peptides and their potential as lead compounds for further optimization and development into therapeutic agents against microbial infections and cancer, subject to more comprehensive safety evaluations in relevant models