Release of IL-1β via IL-1β-Converting Enzyme in a Skin Dendritic Cell Line Exposed to 2,4-Dinitrofluorobenzene

We used a mouse fetal skin dendritic cell line (FSDC) to study the effect of the strong allergen 2,4-dinitrofluorobenzene (DNFB) on interleukin (IL)-1β release and IL-1β receptor immunoreactivity. Stimulation with DNFB (30 minutes) increased IL-1β release without changing the mRNA levels of the protein. Furthermore, DNFB increased transiently the interleukin-1β-converting enzyme (ICE) activity, as measured with its fluorogenic substrate Z-Tyr-Val-Ala-Asp-AFC. The ICE inhibitor Z-YVAD-FMK prevented the release of IL-1β evoked by DNFB. Incubation of the cells with DNFB (30 minutes) strongly increased IL-1β receptor immunoreactivity. The rapid effect of DNFB on the release of mature IL-1β, without inducing an increase of IL-1β mRNA in FSDC, suggests a posttranslational modification of pro-IL-1β by ICE activity

Impact of nanoconfinement on the physical state and conductivity mechanisms of a 2-picolinium ionic liquid crystal

Funding Information: This work was supported by the Associate Laboratory for Green Chemistry LAQV ( UID/QUI/50006/2019 ), i3N (UID/ CTM / 50025/2019 ) and CeFEMA (UID/ CTM / 04540/2019 ), which are financed by national funds from FCT- MCTES and by FEDER funds through the COMPETE 2020 Program. The authors also thank the National Funds through FCT- MCTES and POR Lisboa 2020, under the project numbers PTDC/EAM - AMB / 2023/2021 ( SUSTECH4H2O ), POCI-01-0145-FEDER-007688 and European Interdisciplinary Action ( COST Action CA21159 , PhoBioS). A. F. M. Santos also acknowledges FCT- MCTES for the PhD Grant ( SFRH/BD/132551/2017 ) and I. Matos for the contract CEECIND/004431/2022 . Funding Information: This work was supported by the Associate Laboratory for Green Chemistry LAQV, Portugal, (LA/P/0008/2020, UIDB/50006/2020, UIDP/50006/2020), i3N, Portugal, (LA/P/0037/2020, UIDB/50025/2020, UIDP/50025/2020), CQE, Portugal, (UIDB/00100/2020, UIDP/00100/2020) and CeFEMA, Portugal, (UIDB/04540/2020, UIDP/04540/2020), which are financed by national funds from FCT-MCTES, Portugal, and by FEDER funds through the COMPETE 2020, Portugal, Program. The authors also thank the National Funds through FCT-MCTES, Portugal and POR Lisboa 2020, under the project numbers PTDC/EAM-AMB/2023/2021 (SUSTECH4H2O), POCI-01-0145-FEDER-007688 and European Interdisciplinary Action (COST Action, Belgium, CA21159, PhoBioS). A. F. M. Santos also acknowledges FCT-MCTES, Portugal, for the PhD Grant (SFRH/BD/132551/2017) and I. Matos for the contract CEECIND/004431/2022. Publisher Copyright: © 2024 The Author(s)Hybrid solid-like materials prepared from the incorporation of liquid-like ionic conductors into nanoporous matrices could represent an advantage for a variety of electronic applications. Aiming to obtain such materials, three composites of the polymorphic ionic liquid crystal (ILC) 1-hexadecyl-2-methylpyridinium bromide ([C16-2-Pic][Br]), loaded in the mesoporous inorganic silica SBA-15 (∼6.8 nm in pore diameter), were prepared at guest–host weight fractions of ∼ 40, 60 and 80% (w/w) and investigated by different techniques: ATR-FTIR, BET, TGA, XRD and DSC. Complete amorphisation was achieved for the 40 and 60% composites, while the 80% preparation was stabilised in the low-T morph of native C16, being in the liquid state at room temperature. Furthermore, through Dielectric Relaxation Spectroscopy, the ionic conductivity of the three hybrid materials was characterised, allowing to deconvolute this property in a pure ohmic contribution (conductivity I) and the overlapping of ac − dc transition with interfacial polarisation resulting from the coexistence of the ionic liquid and the quasi-insulating inorganic matrix (conductivity II). From –20 to 20 °C, the conductivity and the corresponding charge migration are faster in all composites relative to the neat ILC, as deduced from the inferior radii of Nyquist arcs. The 60% preparation stood out from the other materials, exhibiting direct conductivity unaffected by electrode polarisation over a larger T-range, leading to the assumption of a nearly continuous silica-mediated charge migration pathway, which is never reached for the 40% composite, while, in the 80% preparation, some C16 deposits on the outer surface of the pores. Incorporation into the silica matrix proved to be a good strategy for the production of cost-efficient materials with long-term stabilisation of the ionic liquid in a single phase over a large range of temperatures, enabling the prediction of flow and conductive properties.publishersversionpublishe

Boat noise impacts Lusitanian toadfish breeding males and reproductive outcome

Anthropogenic noise is a growing threat to marine organisms, including fish. Yet very few studies have addressed the impact of anthropogenic noise on fish reproduction, especially in situ. In this study, we investigated the impacts of boat noise exposure in the reproductive success of wild Lusitanian toadfish (Halobatrachus didactylus), a species that relies on advertisement calls for mate attraction, using behavioural, physiological and reproductive endpoints. Two sets of artificial nests were deployed in the Tagus estuary and exposed to either ambient sound or boat noise during their breeding season. Toadfish males spontaneously used these nests to breed. We inspected nests for occupation and the presence of eggs in six spring low tides (in two years) and assessed male vocal activity and stress responses. Boat noise did not affect nest occupation by males but impacted reproductive success by decreasing the likelihood of receiving eggs, decreasing the number of live eggs and increasing the number of dead eggs, compared to control males. Treatment males also showed depressed vocal activity and slightly higher cortisol levels. The assessment of oxidative stress and energy metabolism-related biomarkers revealed no oxidative damage in noise exposed males despite having lower antioxidant responses and pointed towards a decrease in the activity levels of energy metabolism-related biomarkers. These results suggest that males exposed to boat noise depressed their metabolism and their activity (such as parental care and mate attraction) to cope with an acoustic stressor, consistent with a freezing defensive response/behaviour. Together, our study demonstrates that boat noise has severe impacts on reproductive fitness in Lusitanian toadfish. We argue that, at least fishes that cannot easily avoid noise sources due to their dependence on specific spawning sites, may incur in significant direct fitness costs due to chronic noise exposure.Fundação para a Ciência e Tecnologia - FCTinfo:eu-repo/semantics/publishedVersio

Targeting specific nutrient deficiencies in proteinrestricted diets: some practical facts in PKU dietary management

Among aminoacidopathies, phenylketonuria (PKU) is the most prevalent one. Early diagnosis in the neonatal period with a prompt nutritional therapy (low natural-protein and phenylalanine diet, supplemented with phenylalanine-free amino acid mixtures and special low-protein foods) remains the mainstay of the treatment. Data considering nutrient contents of cooked dishes is lacking. In this study, fourteen dishes specifically prepared for PKU individuals were analysed, regarding the lipid profile and iron and zinc contents. These dishes are poor sources of essential nutrients like Fe, Zn or n-3 fatty acids, reinforcing the need for adequate supplementation to cover individual patients’ needs. This study can contribute to a more accurate adjustment of PKU diets and supplementation in order to prevent eventual nutritional deficiencies. This study contributes to a better understanding of nutrient intake from PKU patients’ meals, showing the need for dietary supplementation

CHEK2 germline variants identified in familial nonmedullary thyroid cancer lead to impaired protein structure and function

Publisher Copyright: © 2024 The AuthorsApproximately 5 to 15% of nonmedullary thyroid cancers (NMTC) present in a familial form (familial nonmedullary thyroid cancers [FNMTC]). The genetic basis of FNMTC remains largely unknown, representing a limitation for diagnostic and clinical management. Recently, germline mutations in DNA repair-related genes have been described in cases with thyroid cancer (TC), suggesting a role in FNMTC etiology. Here, two FNMTC families were studied, each with two members affected with TC. Ninety-four hereditary cancer predisposition genes were analyzed through next-generation sequencing, revealing two germline CHEK2 missense variants (c.962A > C, p.E321A and c.470T > C, p.I157T), which segregated with TC in each FNMTC family. p.E321A, located in the CHK2 protein kinase domain, is a rare variant, previously unreported in the literature. Conversely, p.I157T, located in CHK2 forkhead-associated domain, has been extensively described, having conflicting interpretations of pathogenicity. CHK2 proteins (WT and variants) were characterized using biophysical methods, molecular dynamics simulations, and immunohistochemistry. Overall, biophysical characterization of these CHK2 variants showed that they have compromised structural and conformational stability and impaired kinase activity, compared to the WT protein. CHK2 appears to aggregate into amyloid-like fibrils in vitro, which opens future perspectives toward positioning CHK2 in cancer pathophysiology. CHK2 variants exhibited higher propensity for this conformational change, also displaying higher expression in thyroid tumors. The present findings support the utility of complementary biophysical and in silico approaches toward understanding the impact of genetic variants in protein structure and function, improving the current knowledge on CHEK2 variants’ role in FNMTC genetic basis, with prospective clinical translation.publishersversionpublishe

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

Differentiation stage of myeloma plasma cells: biological and clinical significance

[EN] The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n = 20) that the CD19 − CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferation, replication-history, immunoglobulin-production, and phenotype, consistent with progressively increased differentiation from CD19+CD81+ into CD19 − CD81+ and CD19 − CD81 − BMPCs. Afterwards, we demonstrated in 225 newly diagnosed MM patients that, comparing to normal BMPC counterparts, 59% had fully differentiated (CD19 − CD81 −) clones, 38% intermediate-differentiated (CD19 − CD81+) and 3% less-differentiated (CD19+CD81+) clones. The latter patients had dismal outcome, and PC differentiation emerged as an independent prognostic marker for progression-free (HR: 1.7; P = 0.005) and overall survival (HR: 2.1; P = 0.006). Longitudinal comparison of diagnostic vs minimal-residual-disease samples (n = 40) unraveled that in 20% of patients, less-differentiated PCs subclones become enriched after therapy-induced pressure. We also revealed that CD81 expression is epigenetically regulated, that less-differentiated clonal PCs retain high expression of genes related to preceding B-cell stages (for example: PAX5), and show distinct mutation profile vs fully differentiated PC clones within individual patients. Together, we shed new light into PC plasticity and demonstrated that MM patients harbouring less-differentiated PCs have dismal survival, which might be related to higher chemoresistant potential plus different molecular and genomic profiles