The Toll-dorsal pathway is required for resistance to viral oral infection in Drosophila

Pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. Drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. Here we investigate the role of the Toll pathway in resistance to oral viral infection in D. melanogaster. We show that several Toll pathway components, including Spätzle, Toll, Pelle and the NF-kB-like transcription factor Dorsal, are required to resist oral infection with Drosophila C virus. Furthermore, in the fat body Dorsal is translocated from the cytoplasm to the nucleus and a Toll pathway target gene reporter is upregulated in response to Drosophila C Virus infection. This pathway also mediates resistance to several other RNA viruses (Cricket paralysis virus, Flock House virus, and Nora virus). Compared with control, viral titres are highly increased in Toll pathway mutants. The role of the Toll pathway in resistance to viruses in D. melanogaster is restricted to oral infection since we do not observe a phenotype associated with systemic infection. We also show that Wolbachia and other Drosophila-associated microbiota do not interact with the Toll pathway-mediated resistance to oral infection. We therefore identify the Toll pathway as a new general inducible pathway that mediates strong resistance to viruses with a route-specific role. These results contribute to a better understanding of viral oral infection resistance in insects, which is particularly relevant in the context of transmission of arboviruses by insect vectors.Biotechnology and Biological Sciences Research Council (UK) grant BB/E005470/1, Fundação para a Ciência e Tecnologia fellowships: SFRH/BPD/65985/2009, SFRH/BD/51881/2012, SFRH/51885/2012

Variable Expressivity and Allelic Heterogeneity in Type 2 Familial Partial Lipodystrophy: The p.(Thr528Met) LMNA Variant

Type 2 familial partial lipodystrophy, or Dunnigan disease, is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution. This rare condition results from variants principally affecting exons 8 and 11 of the LMNA gene. In this study, five FPLD2-diagnosed patients carrying the c.1583C>T, p.(Thr528Met) variant in exon 9 of the LMNA gene and with obvious clinical heterogeneity were evaluated. Specific polymorphisms in LMNA and in PPARG were also detected. Exhaustive clinical course, physical examination, biochemical features and family history were recorded, along with the assessment of anthropometric features and body composition by dual-energy X-ray absorptiometry. Preadipocytes obtained from a T528M patient were treated with the classic adipose differentiation medium with pioglitazone. Various adipogenes were evaluated by real-time PCR, and immunofluorescence was used to study intracellular localization of emerin, lamin A and its precursors. As demonstrated with Oil red O staining, the preadipocytes of the T528M patient failed to differentiate, the expression of various adipogenic genes was reduced in the lipodystrophic patient and immunofluorescence studies showed an accumulation of farnesylated prelamin A in T528M cells. We conclude that the T528M variant in LMNA could lead to FPLD2, as the adipogenic machinery is compromisedThis research was funded by the Instituto de Salud Carlos III and the European Regional Development Fund, FEDER (grant number PI081449), and an intramural grant from the Xunta de Galicia (grant number ED431B 2020/37). S.S.I. was awarded a Research Fellowship by the Asociación Española de Familiares y Afectados de Lipodistrofias (AELIP)S

Moving towards personalized medicine - the broad use of aptamers for targeted theranostic

Aptamers are short, single-stranded oligonucleotides synthesized in vitro from a randomized oligonucleotide library against a specific target. These molecules are capable of binding to a wide range of biological targets with high specificity and affinity. They present great advantages over antibodies with potential applications in research, diagnosis, and therapeutics. Specifically for tumors with late-stage identification and poor prognosis, like pancreatic cancer, the study of novel aptamers holds tremendous potential for cancer diagnosis and treatment. Along with cancer treatment, aptamers have also shown high potential in regulating the immune response and modulating several critical steps of signaling cascades, such as in immune checkpoints. In the context of microbiota and infection, aptamers are being studied to identify microbes and their metabolites. This assessment has the potential to improve the detection and management of infectious diseases while assisting us in better understanding health risks and treatment outcomes by tracking changes in the microbiota. In this review, the potential of aptamers is explored regarding their applications in cancer, immune, and microbiota therapy.Pilar Baylina (P.B.) acknowledges on the behalf of the authors the support of Fundação para a Ciência e Tecnologia (FCT), Portuguese Government, under the Strategic Project Reference: UID/BIM/04293/2013. Pilar Baylina (P.B.) and R.F. was also supported by FEDER/02/SAICT/2020/072560. Ana Cláudia Pereira (A.C.P.) acknowledges the support of Fundação para a Ciência e Tecnologia (FCT), Portuguese Government, under the Strategic Project Reference: 2022.09032.PTDC. André P. Sousa acknowledges FCT for the PhD grant 2022.12441.BD. Ana C. Rocha acknowledges FCT for the PhD grant 2021.06521.BD. Patrick P. Pais acknowledges FCT for the PhD grant 2021.09498.BD. Susana Ramalho acknowledges LaBMI for the PhD grant LABMI/BI/2021/01 (NEURO4COVID).info:eu-repo/semantics/publishedVersio

Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.S

Both “illness and temptation of the enemy”: melancholy, the medieval patient and the writings of King Duarte of Portugal (r. 1433–38)

Recent historians have rehabilitated King Duarte of Portugal, previously maligned and neglected, as an astute ruler and philosopher. There is still a tendency, however, to view Duarte as a depressive or a hypochondriac, due to his own description of his melancholy in his advice book, the Loyal Counselor. This paper reassesses Duarte's writings, drawing on key approaches in the history of medicine, such as narrative medicine and the history of the patient. It is important to take Duarte's views on his condition seriously, placing them in the medical and theological contexts of his time and avoiding modern retrospective diagnosis. Duarte's writings can be used to explore the impact of plague, doubt and death on the life of a well-educated and conscientious late-medieval ruler

Study on the efficiency and effectiveness of public spending on tertiary education Third report (second draft)

Public tertiary education systems in the EU Member States are studied by comparing used resources with education and research outputs and outcomes. Efficiency in public tertiary education systems across EU countries plus Japan and the US is assessed with semi-parametric methods and stochastic frontier analysis. A core group of efficient countries is identified. A good quality secondary system, output-based funding rules, institutions’ independent evaluation, and staff policy autonomy are positively related to efficiency. Moreover, evidence is provided that public spending on tertiary education is more effective in what concerns labour productivity growth and employability when it is coupled with efficiency. .info:eu-repo/semantics/publishedVersio

Business ethics: a study of Portuguese social representation of business ethics

Ever since the 1980s, the business ethics field has gone through significant changes. There is now a vast body of business ethics literature concerned with diverse topics and themes, but relating the field of business ethics with social representations is not one of them, with this article being the first, to our knowledge, to do so with a Portuguese sample (N = 2,735). Attempting to provide a ‘bridge’ between theory and reality, we proceeded with this study, trying to discover the social representation of business ethics in Portuguese workers using the free evocation test and applying Abric’s central nucleus theory. The results show a central core organised around the concepts of ‘respect’, ‘justice’, ‘honesty’, ‘equality’, ‘code of conduct’, ‘confidentiality’ and ‘fair competition’. While some of the core concepts of business ethics are directly found in the literature, others were not, pointing to a possible partition between theory and reality

Esparto wool as reinforcement in hybrid polyurethane composite foams

In the present work polyurethane foams containing variable concentrations of nano-sized clay and esparto wool were prepared and studied, with the objective of developing new multi-scalar rigid foams. The addition of montmorillonite clay favoured foaming and the formation of finer and homogeneous cellular structures, resulting in foams with compressive elastic moduli and collapse stresses lower than that of the polyurethane foams. Nevertheless, a comparative analysis versus the foams’ relative density demonstrated that both properties follow one single trend for the two materials. The combination of esparto and montmorillonite further reduced the cell size of foams, at the same time promoting higher open cell contents, resulting in the foams with the lowest mechanical properties. Although no important differences in thermal conductivity were found with adding montmorillonite, its value decreasing with reducing the relative density, the incorporation of esparto led to higher thermal conductivities, independently of the relative density. The combination of esparto and montmorillonite resulted in foams with thermal conductivities halfway between the esparto-reinforced and the montmorillonite-reinforced foams, related to a higher open cell content.Peer Reviewe

The Perception of Business Ethics in the Public and Private Sector: A study of Portuguese Social Representations

Over the years, people have become more aware of how companies influence their lives, communities, and the environment. This influence has led to a growing interest and a vast and distinct literature in business ethics. Despite the diversity of themes concerning business ethics, the literature concerning social representations of business ethics in public and private sectors is scarce. This article explores the differences and similarities of Portuguese social representation between two business sectors (public and private). A Free Evocations Test was applied for that purpose, and the answers were analyzed using EVOC software. The results interpreted based on Abric’s Theory of the Central Nucleus showed a central core organized around the concept of ‘respect’ in the two business sectors and ‘responsibility’, ‘honesty’, ‘justice’, ‘code of conduct’, ‘confidentiality’ and ‘ethic’ in the central core of the private sector