Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection

CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes. The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells. Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies. However, the structural variability conferred by both the alternative splicing and CD44 protein glycosylation is disregarded. In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies. We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection. These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE, grant numbers POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274; OCI-01-0145-FEDER-031028; and national funds through the Foundation for Science and Technology (FCT), grant numbers PTDC/BBB-EBI/0567/2014 (to CAR), UID/BIM/04293/2013, and PTDC/MED-QUI/29780/2017; and the project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). F. Pinto received a fellowship from FCT (SFRH/BPD/115730/2016)

Back to replacement migration: a new European perspective applying the prospective-age concept

Background: The UN Replacement Migration report (2000) had a significant impact in academic and civil society. Its approach consisted of estimating the migration volumes required to mitigate the effects of population decline and ageing. The volume of migrants required to prevent population decline and sustain the working-age population was not particularly high, but the vast number of migrants needed to maintain the potential support ratio was highlighted as an unrealistic goal. Objective: In this paper the UN exercise is revisited and updated by deploying the concept of prospective age to overcome a strict chronological definition of the working-age population. The replacement migration approach is developed from a new European perspective, the temporal series is extended for an additional decade, and alternative operative age-group definitions are compared by projecting replacement migration estimations according to both classic (conventional) and dynamic (prospective) age limits. Conclusions: The key conclusions of the original UN publication are reasserted. In many countries the replacement migration volumes needed to sustain the decline in total population and working-age population are of an order of magnitude similar to recent observed migration. However, even under the prospective-age approach the halt of the ageing process – expressed as the maintenance of the current potential support ratio – remains an unrealistic target. Contribution: We propose the deployment of the prospective-age concept to define dynamic age limits in the definition of working-age population. Because the prospective-age concept is flexible it will be possible to explore other dimensions from this perspective in the future, increasing the analytical potential of replacement migration estimations as a valuable contribution to the demographic ageing debate.info:eu-repo/semantics/publishedVersio

Physical-chemical properties of cross-linked chitosan electrospun fiber mats

Chitosan fiber mats were successfully processed by electrospinning. The as-spun fiber mats were neutralized with ethanol and cross-linked with glutaraldehyde. A decrease of the fiber average diameter from 243 ± 43 nm down to 215.53 nm was observed for the neutralized and cross-linking chitosan membrane. It was found that the processing conditions do not alter the initial deacetylation degree of the polymer. Polymer crystallinity index showed a decrease from 61 % for the Protasan material down to 17 % for the cross-linking fiber mats. A swelling index up to 1000 % was observed for the cross-linked samples. Preliminary MC-3T3-E1cell culture results showed good cell adhesion and proliferation in the cross-linked chitosan fiber mats.This work is funded by FEDER funds through the "Programa Operacional Factores de Competitividade – COMPETE" and by national funds by FCT- Fundação para a Ciência e a Tecnologia, project references NANO/NMed-SD/0156/2007. V.S. and SM thanks the FCT grants SFRH/BPD/63148/2009 and SFRH/BPD/64726/2009, respectively. The authors also thank the support of the COST Action MP1003, 2010 ‘European Scientific Network for Artificial Muscles’ (ESNAM). JLGR acknowledge the support of the Spanish Ministry of Science and Innovation through project No. MAT2010-21611-C03-01 (including the FEDER financial support) and Programa Nacional de Internacionalización de la I+D project EUI2008-00126. The authors also thank the National NMR Network (National Program for Scientific Re-equipment, REDE/1517/RMN/2005, funds from POCI 2010 (FEDER) and FCT) and Microscopy Service of the UPV for the use of their lab

Serum amyloid A proteins reduce bone mass during mycobacterial infections

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFN gamma- and TNF alpha-dependent manner. IFN gamma produced during infection enhanced macrophage TNF alpha secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.This article is a result of the project HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (NORTE-01-0145-FEDER-000039), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was supported by KOG-202108-00929 from the European Haematology Society, awarded to AG. Work in the MS lab was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028955 (PTDC/SAU-INF/28955/2017). AG and MS are supported by an Individual Scientific Employment contract (CEECIND/00048/2017; CEECIND/00241/2017 respectively). DS acknowledges the Portuguese Foundation for Science and Technology (FCT) for the Post-Doc fellowship (SFRH/BPD/115341/2016). RP, DS and AF have PhD grants (SFRH/BD/145217/2019; SFRH/BD/143536/2019; 2020.05949.BD, respectively) financed by FCT

Data-Driven Modeling of the Cellular Pharmacokinetics of Degradable Chitosan-Based Nanoparticles

Nanoparticle drug delivery vehicles introduce multiple pharmacokinetic processes, with the delivery, accumulation, and stability of the therapeutic molecule influenced by nanoscale processes. Therefore, considering the complexity of the multiple interactions, the use of data-driven models has critical importance in understanding the interplay between controlling processes. We demonstrate data simulation techniques to reproduce the time-dependent dose of trimethyl chitosan nanoparticles in an ND7/23 neuronal cell line, used as an in vitro model of native peripheral sensory neurons. Derived analytical expressions of the mean dose per cell accurately capture the pharmacokinetics by including a declining delivery rate and an intracellular particle degradation process. Comparison with experiment indicates a supply time constant, τ = 2 h. and a degradation rate constant, b = 0.71 h−1. Modeling the dose heterogeneity uses simulated data distributions, with time dependence incorporated by transforming data-bin values. The simulations mimic the dynamic nature of cell-to-cell dose variation and explain the observed trend of increasing numbers of high-dose cells at early time points, followed by a shift in distribution peak to lower dose between 4 to 8 h and a static dose profile beyond 8 h

Gravitational spectral shift caused by Casimir stresses

The linearized Einstein field equations with the renormalized stress tensor of a massless quantum scalar field as source are solved in the 4-dimensional spacetime near an infinite plane boundary. The motion of particles and light is investigated disclosing a variety of effects. For instance, it is shown that light rays initially parallel to the boundary do not bend. On the other hand, under the same initial conditions, particles will be affected by the presence of the quantum field, being accelerated toward the plane boundary or departing from it depending on the value of the curvature coupling parameter {\xi}. It is suggested that {\xi} can be set by measuring the spectral deviation of a light ray travelling perpendicularly to the boundary.Comment: 4 pages, 1 figure, published versio

Endocrine disruptive action of diclofenac and caffeine on Astyanax altiparanae males (Teleostei: Characiformes: Characidae)

Diclofenac (DCF) and caffeine (CAF) are persistent pharmaceuticals that occur in mixtures in the aquatic ecosystems causing effects in the reproductive physiology of aquatic organisms. This study evaluated the physiological reproductive responses of Astyanax altiparanae males exposed to nominal concentrations of DCF (3.08 mg L− 1) and CAF (9.59 mg L− 1) separately and combined, for 96 h. The steroids profile, estrogenic biomarker vitellogenin (vtgA), testes and liver morphology, and also mortality of males were assessed. DCF and CAF degradation was 5% of the initial concentration for 24 h. The LC50 of the DCF and CAF were 30.8 mg L− 1 and 95.9 mg L− 1, respectively. Males exposed to DCF and CAF exhibited a reduction of 17β-Estradiol (E2) concentration compared to control (CTL). Similarly, testosterone (T) was also reduced in the DCF treatment, but this response was not observed in 11-Ketotestosterone (11-KT). Males exposed to DCF + CAF combined did not exhibit differences in T, E2 and 11-KT steroids. The vtgA gene expression and the sperm concentration did not change among the treatments. Moreover, acute exposure revealed a hypertrophy of hepatocytes cells in the DCF and DCF + CAF treatments. In conclusion, DCF and CAF, isolated, exhibit an endocrine disruptive activity in A. altiparanae male, an opposite response observed with the mixture of both compounds that abolishes the endocrine disruptive effects. DCF seems to be more toxic for this species, altering also hepatocytes morphology.Fil: Godoi, Filipe G.A.. Universidade de Sao Paulo; BrasilFil: Muñoz Peñuela, Marcela. Universidade de Sao Paulo; BrasilFil: Olio Gomes, Aline D.. Universidade de Sao Paulo; BrasilFil: Tolussi, Carlos E.. Universidade Anhembi-Morumbi; BrasilFil: Brambila Souza, Gabriela. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Branco, Giovana S.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Lo Nostro, Fabiana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Moreira, Renata. Universidade de Sao Paulo; Brasi

Iron bioavailability of carotenoids and iron enhanced content crops.

The aim of the study was to evaluate the iron bioavailability of bean and a mix of bean and rice and/or sweet potatoes and/or pumpkin and analyzing the influence of carotenoids on iron bioavailability

Setting the stage for new ecological indicator species: A holistic case study on the Iberian dolphin freshwater mussel Unio delphinus Spengler, 1793

Supplementary data to this article can be found online at https://doi.org/10.1016/j.ecolind.2019.105987.Due to their sensitivity and dramatic declines, freshwater mussels are prime targets for conservation and environmental monitoring. For this, however, information is needed on life history and ecological traits, which is lacking in many taxa, including threatened species. Species recently described or recognized as valid are of particular concern, due to the shortage of even basic knowledge. A case in point is the recently recognized and Near Threatened dolphin freshwater mussel Unio delphinus Spengler, 1793, which is endemic to the western Iberian Peninsula and has suffered marked population declines. To overcome information gaps for U. delphinus, we carried out a holistic biological study across the species range, aiming to: i) estimate the area of occupancy (AOO) and extent of occurrence (EOO) based on updated distribution data taken from the literature and recent surveys; ii) estimate growth patterns from biometrical (shell dimensions and growth annuli) measurements taken on specimens from seven populations; iii) estimate sex ratios from gonad tissue biopsies collected on specimens from eight populations; iv) estimate gametogenesis and sex ratio through histological examination of gonad and gill tissues collected monthly for a year, from a single population; and v) determine host species from infestation trials of glochidia with co-occurring fish species. We estimated an EOO of 706 km2 and an AOO of 61 km2, which together with data on declines assigns the species to the Endangered category using IUCN criteria. Unio delphinus was found to grow faster and to be shorter-lived (up to 11 years, maturity at around 2 years old) than other European freshwater mussels. Growth and life span are similar across the range in lotic habitats, but different from that in lentic habitats. The larvae of U. delphinus may attach to most co-occurring fish species, but only native species were effective hosts. Native cyprinids, especially those from the genus Squalius, seem to be the primary hosts. Overall, the information provided contributes to a better conservation status assessment, selection of conservation and rehabilitation areas, guidance for the establishment of propagation programs and better timing for specimens’ manipulation including monitoring and possible translocations. The framework presented here highlights the importance of basic biological studies to define good ecological and physiological status.This work was supported by Portuguese FCT – Foundation for Science and Technology, Projects FRESHCO: Multiple implications of invasive species on Freshwater Mussel co-extinction processes (PTDC/AGR-FOR/1627/2014-04/SAICT/2015), MUSSELFLOW: Host-depen dent evolution, ecology and conservation of freshwater mussels under varying hydrological conditions: consequences of climate change (PTDC/BIA-EVL/29199/2017), and ConBiomics: The missing approach for the Conservation of freshwater Bivalves Project N° NORTE-01-0145- FEDER-030286, co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF. FCT also supported MLL under grant (SFRH/BD/115728/2016), CM under grant (SFRH/BD/111133/ 2015) and also through Strategic Funding UID/Multi/04423/2019. PB was supported by EDP Biodiversity Chair