A role for the small GTPases RAC1 and RAC1b in the modulation of NIS expression: potentiation of therapy with radioactive iodine in differentiated thyroid carcinoma

Introduction or Background: The Sodium Iodide Symporter (NIS) is responsible for active transport of iodide into thyroid follicular cells. The retention of its functional expression in most of the well-differentiated thyroid carcinomas (DTCs) enables the use of radioactive iodine (RAI) for treatment of metastatic disease. Still, about 30% of patients with advanced forms of DTC became refractory to RAI which makes their management very challenging. The main reason for impaired iodide uptake in refractory-DTC is the defective functional expression of NIS. Several molecular players have been described as critical for TSH-induced NIS expression, an example being the p38 mitogenic kinase. In breast cancer cells, the small GTPase RAC1 was shown to mediate the positive impact of p38 kinase activity on NIS expression. We, on the other hand, have previously shown that overexpression of RAC1b, a tumor-related splicing variant of RAC1, is associated with worse outcomes in DTC and correlates with the MAPK-activating BRAFV600E mutation, which has been related to the loss of NIS. Since RAC1 and RAC1b may act in an antagonistic fashion to regulate specific cellular responses, we asked if RAC1b would be implicated in NIS downregulation observed in DTCs. Methods Section: NIS expression levels were analyzed by RT-qPCR in a RAC1/RAC1b expression model system developed in non-transformed thyroid cell lines. A non-radioactive iodide influx assay was used to confirm the impact of RAC1-signaling on the efficacy of iodide uptake. Results Section: We demonstrate that ectopic overexpression of RAC1b is sufficient to decrease TSH-induced NIS expression, antagonizing the positive effect of RAC1 GTPase. Moreover, we clearly document, for the first time in thyroid cells, that both NIS expression and iodide uptake are downregulated upon RAC1 inhibition, supporting the role of canonical RAC1 signaling in promoting TSH-induced NIS expression. Conclusion: Our findings provide evidence that RAC1 and RAC1b signaling are implicated in the regulation of NIS expression in thyroid cells and suggest that RAC1b overexpression may be one of the mechanisms contributing to the low levels of NIS observed in some subgroups of DTCs, antagonizing RAC1 stimulatory effect on the TSH/cAMP-mediated induction of NIS expression.FCT - PTDC/BIAMOL/31787/2017N/

Effect of protrusions on cathodic-arc-attachment mode in high-pressure arc discharges

It is shown via computer simulations that a protru sion on a thermionic arc cathode may dramatically change the pattern of steady-state modes of current transfer. This happens through a bifurcation of a special type occurring at certain geom etry of the cathode and may play a role in operation of electrodes of compact high-intensity discharge lamps.info:eu-repo/semantics/publishedVersio

Lipid nanocarriers for anti-HIV therapeutics: a focus on physicochemical properties and biotechnological advances

Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life, and poor penetration into HIV reservoir sites, which contribute to the suboptimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review is focused on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARV to overcome biological barriers upon administration. Furthermore, a correlation between these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference (RNAi) delivery for the treatment of HIV infections were also discussed.This research was funded by FCT/MCTES—Foundation for Science and Technology I.P. from the Minister of Science, Technology, and Higher Education (PIDDAC) and European Regional Development Fund (ERDF) by the COMPETE—Programa Operacional Factores de Competitividade (POFC) through the project CONCERT [POCI-01-0145-FEDER-032651 and PTDC/NANMAT/326512017] and the Strategic Funding UID/FIS/04650/2019 and “Contrato-Programa” UIDB/ 04469/2020 (CF-UM-UP and CBMA). Marlene Lúcio thanks FCT and ERDF for the doctoral position [CTTI-150/18-CF (1)] in the scope of the project CONCERT. Maria João Faria thanks FCT for PhD grant [2020.06561.BD]

Cardiac venous arterialization in acute myocardial infarction: how great is the benefit?

Cardiac venous arterialization has been proposed as an alternative approach for myocardial revascularization in ischaemic heart disease. It is based on using the cardiac venous system to transport arterial blood from a systemic artery to infarcted myocardial areas. Our goal was to evaluate its benefit in reducing acute myocardial infarct size and its effects on cardiac performance. In a group of pigs, the left internal mammary artery was anastomosed to the left anterior descending vein; this vein was ligated proximally. The left anterior descending coronary artery was also occluded. Over 5 days, several diagnostic procedures were used to characterize and measure the extent of myocardial infarct, namely ECG, echocardiography, cardiac biomarkers and histopathology. Data were compared with those from a control group of pigs, which were submitted to ligation of only the left anterior descending coronary artery. In the experimental group, echocardiography revealed that the ejection fraction and thickness of the ventricular walls remained unchanged 4 days after surgery, in contrast to the major alterations in the control group. In fact, the ejection fraction in the control group decreased by 21% (P 0.2). This study reveals that selective cardiac venous arterialization can nourish the myocardium and is able to reduce infarct size by more than 50%, while protecting cardiac performance. We believe, therefore, that further investigation should be carried out into this technique in order for it to be considered as an option in coronary surgery

Foliar treatments as a strategy to control iron chlorosis in orange trees

Different foliar treatments were applied to evaluate the recovery of iron chlorosis of orange trees (Citrus sinensis (L.) Osb. cv. 'Valencia late') grown on a calcareous soil. The treatments were: Fe (II) sulphate (500 mg Fe L-1), sulphuric acid (0.5 mM H2SO4), Fe (III)-chelate (Hampiron 654 GS, 120 mg Fe L-1) and distilled water as a control. The recovery from iron chlorosis was evaluated with the SPAD-502 apparatus and the values converted to total chlorophyll concentration. The effects of treatments on the mineral composition of leaves and flowers, and the size and quality of fruits were evaluated. The residual effect of treatments was also evaluated one year later. In orange trees, the use of frequent foliar sprays with Fe was able to alleviate Fe chlorosis and prevented yield and quality losses caused by Fe chlorosis. Compared with the control, sprays of Fe (II) sulphate led to higher concentrations of chlorophyll, Fe and Zn in leaves and flowers at the end of the experimental period, and significantly improved fruit size and quality. Leaf Fe concentration increased after the sulphuric acid spray, but this treatment did not affect fruit quality parameters. The mineral composition of flowers and leaves was correlated with some fruit quality parameters obtained one year later. These results suggest that foliar sprays with Fe could help to avoid fruit quality losses caused by Fe chlorosis in citrus orchards

Bioactivity of Monoterpene Alcohols as an Indicator of Biopesticidal Essential Oils against the Root Knot Nematode Meloidogyne ethiopica

The application of pesticides remains one of the most efficient control methods for phytophagous parasites in crops. Essential oils (EOs) are complex mixtures of highly active compounds that can be used as biopesticides against plant parasitic nematodes. In the present work, the antinematodal activity of the monoterpene alcohols geraniol, linalool, menthol or  -terpineol, which are generally found in high amounts in EOs of some aromatic and medicinal plants, was analyzed on the root knot nematode Meloidogyne ethiopica. Geraniol showed intense and lasting antinematodal activity, suggesting that EOs rich in this compound can be used in the development of nematicidal biopesticides to integrate sustainable pest management strategies against this pest

Tailoring carbon nanotubes surface chemistry for the purification of antileukemic drugs

Biopharmaceuticals have been used to overcome fatal diseases related with aging. L-aspariginase (LA), in particular, has shown evidences of being efficient for leukemia therapy. The LA production and purification require several steps increasing the cost of the process. In this work, functionalized carbon nanotubes (CNTs) were studied as a cost-effective support to purify LA. It was shown that CNTs have strong affinity for the target biopharmaceutical, meaning that can be a promising alternative for the adsorption and purification of LA.publishe

Gyrodactylus orecchiae sp. n. (Monogenea: Gyrodactylidae) from farmed populations of gilthead seabream (Sparus aurata) in the Adriatic Sea

Gyrodactylus orecchiae sp. n. (Monogenea, Gyrodactylidae) is described from the skin, fins, eyes and gills of juvenile Sparus aurata L. (gilthead seabream) following two outbreaks of gyrodactylosis amongst stocks held in inshore floating cages on the Adriatic coast of Albania and Croatia. Fish were heavily infected (1000+ gyrodactylids/fish) with G. orecchiae which reportedly resulted in ~2–10% mortality amongst the infected stock. Morphologically, the haptoral hooks of G. orecchiae most closely resemble those of Gyrodactylus arcuatus Bychowsky, 1933 in the approximate shape of the ventral bar with its pronounced ventral bar processes and marginal hook sickles which possess a square line to the inner edge of the sickle blade and large rounded heels. The marginal hooks are also morphologically similar to those of Gyrodactylus quadratidigitus Longshaw, Pursglove et Shinn, 2003 and Gyrodactylus colemanensis Mizelle et Kritsky, 1967, but G. orecchiae can be readily discriminated from all three species by the characteristic infolding of the hamuli roots and the shape of the marginal hook sickle. Molecular sequencing of the ITS1, 5.8S, ITS2 regions (513+157+404 bp, respectively) of G. orecchiae and alignment with other gyrodactylids for which these same genomic regions have been determined, suggests that this is a new species. No similarities were found when the ITS1 region of G. orecchiae was compared with 84 species of Gyrodactylus available on GenBank

Enhanced biocatalytic sustainability of laccase by immobilization on functionalized carbon nanotubes/polysulfone membranes

Chemically functionalized multi-walled carbon nanotubes (CNTs) are used as carriers for laccase immobilization. In this work, CNTs were modified using different approaches with a combination of methods involving hydrothermal oxidation with nitric acid, treatment with 3-aminopropyltriethoxysilane, glutaraldehyde, N-ethyl-N-(3-(dimethylamino)-propyl) carbodiimide hydrochloride and N-hydroxysuccinimide. The enzyme immobilization efficiency and recovered activity were evaluated towards 2,2′-azino-bis(3-ethylbenzathiazoline-6-sulfonic acid) biocatalytic oxidation. The best compromise between immobilization efficiency and recovered activity was obtained using the CNTs functionalized with 0.3 M HNO3, treated with N-ethyl-N-(3-(dimethylamino)propyl) carbodiimide hydrochloride and N-hydroxysuccinimide. This catalyst also showed the best thermal stability (at 50 and 60 °C). The bioconjugate based on this material was characterized by vibrational spectroscopies (FTIR and Raman) and by N2 adsorption. The results from reutilization tests showed that laccase activity was kept above 65% of its initial value after five consecutive cycles of reuse. The biocatalytic performance of the immobilized enzyme was evaluated for the degradation of a mixture of phenolic compounds in water containing phenol, resorcinol, 4-methoxyphenol and 4-chlorophenol. As means of cost efficient to enzyme reutilization, laccase was immobilized over polysulfone membranes blended with the functionalized CNTs and studied in the degradation of 4-methoxyphenol.This work was financially supported by Projects POCI-01-0145-FEDER-006984 – Associate Laboratory LSRE-LCM and POCI-01-0145-FEDER-031268 funded by FEDER through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) – and by national funds and by national funds (OE), through FCT/MCTES - Fundação para a Ciência e a Tecnologia. The work was developed in the scope of the project CICECO-Aveiro Institute of Materials (Ref. FCT UID/CTM/50011/2013), financed by national funds through the FCT/MEC and co-financed by FEDER under the PT2020 Partnership Agreement. M.C.N. acknowledges FCT the post-doctoral grants SFRH/BPD/110423/2015. M.J.L. acknowledges FCT for the research grant PD/BD/52623/2014, while C.G.S. and M.J.S. acknowledge the FCT Investigator Programme (IF/00514/2014) with financing from the European Social Fund and the Human Potential Operational Programme. A.P.M. Tavares acknowledges FCT for the research contract under the IF (IF/01634/2015) Investigator Programme. S.M.T. acknowledges the financial support from the University of Granada, Programme: “Proyectos de Investigación para la Incorporación de Jóvenes Doctores“. We are indebted to Dr. Carlos Sá and the CEMUP team (Portugal) for technical assistance and advice with SEM/EDXS measurements.publishe

Co2 efflux, co2 concentration and photosynthetic refixation in stems of Eucalyptus globulus (Labill.)

Research PaperIn spite of the importance of respiration in forest carbon budgets, the mechanisms by which physiological factors control stem respiration are unclear. An experiment was set up in a Eucalyptus globulus plantation in central Portugal with monoculture stands of 5-year-old and 10-year-old trees. CO2 efflux from stems under shaded and unshaded conditions, as well as the concentration of CO2 dissolved in sap [CO2 *], stem temperature, and sap flow were measured with the objective of improving our understanding of the factors controlling CO2 release from stems of E. globulus. CO2 efflux was consistently higher in 5-year-old, compared with 10-year-old, stems, averaging 3.4 versus 1.3 mmol m22 s21, respectively. Temperature and [CO2 *] both had important, and similar, influences on the rate of CO2 efflux from the stems, but neither explained the difference in the magnitude of CO2 efflux between trees of different age and size. No relationship was found between efflux and sap flow, and efflux was independent of tree volume, suggesting the presence of substantial barriers to the diffusion of CO2 from the xylem to the atmosphere in this species. The rate of corticular photosynthesis was the same in trees of both ages and only reduced CO2 efflux by 7%, probably due to the low irradiance at the stem surface below the canopy. The younger trees were growing at a much faster rate than the older trees. The difference between CO2 efflux from the younger and older stems appears to have resulted from a difference in growth respiration rather than a difference in the rate of diffusion of xylemtransported CO