druggable targets in cancer

Funding: iNOVA4Health—UID/Multi/04462/, a programme financially supported by Fundação para a Ciência e a Tecnologia-Ministério da Educação e Ciência (FCT-MCTES) through national funds.To enable survival in adverse conditions, cancer cells undergo global metabolic adaptations. The amino acid cysteine actively contributes to cancer metabolic remodelling on three different levels: first, in its free form, in redox control, as a component of the antioxidant glutathione or its involvement in protein s-cysteinylation, a reversible post-translational modification; second, as a substrate for the production of hydrogen sulphide (H2S), which feeds the mitochondrial electron transfer chain and mediates per-sulphidation of ATPase and glycolytic enzymes, thereby stimulating cellular bioenergetics; and, finally, as a carbon source for epigenetic regulation, biomass production and energy production. This review will provide a systematic portrayal of the role of cysteine in cancer biology as a source of carbon and sulphur atoms, the pivotal role of cysteine in different metabolic pathways and the importance of H2S as an energetic substrate and signalling molecule. The different pools of cysteine in the cell and within the body, and their putative use as prognostic cancer markers will be also addressed. Finally, we will discuss the pharmacological means and potential of targeting cysteine metabolism for the treatment of cancer.publishersversionpublishe

Size and frequency of natural forest disturbances and Amazon carbon balance

Forest inventory studies in the Amazon indicate a large terrestrial carbon sink. However, field plots may fail to represent forest mortality processes at landscape-scales of tropical forests. Here we characterize the frequency distribution of disturbance events in natural forests from 0.01 ha to 2,651 ha size throughout Amazonia using a novel combination of forest inventory, airborne lidar and satellite remote sensing data. We find that small-scale mortality events are responsible for aboveground biomass losses of B1.28 Pg C y 1 over the entire Amazon region. We also find that intermediate-scale disturbances account for losses of B0.01 Pg C y 1 , and that the largest-scale disturbances as a result of blow-downs only account for losses of B0.003 Pg C y 1 . Simulation of growth and mortality indicates that even when all carbon losses from intermediate and large-scale disturbances are considered, these are outweighed by the net biomass accumulation by tree growth, supporting the inference of an Amazon carbon sink

Novel Perspectives in Management of Angiogenesis and Cancer Therapy

Funding: The project was funded by IPOLFG EPE and by iNOVA4Health (UID/Multi/04462/2019) a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds. We also acknowledge funding from FCT-MCTES through the project DREAM—PTDC/MEC-ONC/29327/2017. FL-C PhD fellowship was funded by FCT (PD/BD/128337/2017).The activation of endothelial cells (ECs) is a crucial step on the road map of tumor angiogenesis and expanding evidence indicates that a pro-oxidant tumor microenvironment, conditioned by cancer metabolic rewiring, is a relevant controller of this process. Herein, we investigated the contribution of oxidative stress-induced ferroptosis to ECs activation. Moreover, we also addressed the anti-angiogenic effect of Propranolol. We observed that a ferroptosis-like mechanism, induced by xCT inhibition with Erastin, at a non-lethal level, promoted features of ECs activation, such as proliferation, migration and vessel-like structures formation, concomitantly with the depletion of reduced glutathione (GSH) and increased levels of oxidative stress and lipid peroxides. Additionally, this ferroptosis-like mechanism promoted vascular endothelial cadherin (VE-cadherin) junctional gaps and potentiated cancer cell adhesion to ECs and transendothelial migration. Propranolol was able to revert Erastin-dependent activation of ECs and increased levels of hydrogen sulfide (H2S) underlie the mechanism of action of Propranolol. Furthermore, we tested a dual-effect therapy by promoting ECs stability with Propranolol and boosting oxidative stress to induce cancer cell death with a nanoformulation comprising selenium-containing chrysin (SeChry) encapsulated in a fourth generation polyurea dendrimer (SeChry@PUREG4). Our data showed that novel developments in cancer treatment may rely on multi-targeting strategies focusing on nanoformulations for a safer induction of cancer cell death, taking advantage of tumor vasculature stabilization.publishersversionpublishe

Risk assessment due to terrorist actions on public transportation networks : a case study in Portugal

The work presented in this paper was performed in collaboration with one of the largest Public Transportation Operator in Portugal and addresses the problem of risk assessment due to terrorist actions involving explosions at different levels. First, a region of the Operator is selected. The elements in the Operator's network with the highest associated risk are highlighted for each threat using the COUNTERACT guidelines. Subsequently, from the group of elements with the highest associated risk, an element is selected for structural safety evaluation under blast loading. Through numerical analysis, different explosion scenarios are studied and the behavior of the structure is presented.This work was performed under Project CH-SECURE, with reference PTDC/ECM/120118/2010, funded by the Portuguese Foundation of Science and Technology - FCT. The authors acknowledge the support. The first author also acknowledges the support from his PhD FCT grant with the reference SFRH/BD/45436/2008

Novos registros de moscas-das-frutas (Diptera: Tephritidae), hospedeiros silvestres e parasitóides (Hymenoptera: Braconidae) na Amazônia brasileira

Anastrepha anomala Stone was obtained from Parahancornia amapa (Huber) Ducke (Apocynaceae) fruits, and Anastrepha hastata Stone from Cheiloclinium cognatum (Miers.) (Hippocrateaceae) in the State of Amapá, Brazil. Two braconids, Doryctobracon sp. and Opius bellus Gahan, were reared from the latter fruit fly species. This is the first record of P. amapa as a fruit fly host. C. cognatum is the first host known to A. hastata. Both braconids are also the first records of parasitoids for this species.Anastrepha anomala Stone foi obtida de frutos de Parahancornia amapa (Huber) Ducke (Apocynaceae) e Anastrepha hastata Stone de Cheiloclinium cognatum (Miers.) (Hippocrateaceae) no Amapá, sendo obtidos dois braconídeos, Doryctobracon sp. e Opius bellus Gahan, dessa espécie. Este é o primeiro registro de P. amapa como hospedeiro de moscas-das-frutas. C. cognatum é o primeiro hospedeiro conhecido de A. hastata e os braconídeos são também os primeiros registros de parasitóides dessa espécie.Agência de Desenvolvimento da Amazônia and Secretaria de Estado da Ciência e Tecnologia do Amap

Soil biochemistry and microbial activity in vineyards under conventional and organic management at Northeast Brazil.

The São Francisco Submedium Valley is located at the Brazilian semiarid region and is an important center for irrigated fruit growing. This region is responsible for 97% of the national exportation of table grapes, including seedless grapes. Based on the fact that orgThe São Francisco Submedium Valley is located at the Brazilian semiarid region and is an important center for irrigated fruit growing. This region is responsible for 97% of the national exportation of table grapes, including seedless grapes. Based on the fact that organic fertilization can improve soil quality, we compared the effects of conventional and organic soil management on microbial activity and mycorrhization of seedless grape crops. We measured glomerospores number, most probable number (MPN) of propagules, richness of arbuscular mycorrhizal fungi (AMF) species, AMF root colonization, EE-BRSP production, carbon microbial biomass (C-MB), microbial respiration, fluorescein diacetate hydrolytic activity (FDA) and metabolic coefficient (qCO2). The organic management led to an increase in all variables with the exception of EE-BRSP and qCO2. Mycorrhizal colonization increased from 4.7% in conventional crops to 15.9% in organic crops. Spore number ranged from 4.1 to 12.4 per 50 g-1 soil in both management systems. The most probable number of AMF propagules increased from 79 cm-3 soil in the conventional system to 110 cm-3 soil in the organic system. Microbial carbon, CO2 emission, and FDA activity were increased by 100 to 200% in the organic crop. Thirteen species of AMF were identified, the majority in the organic cultivation system. Acaulospora excavata, Entrophospora infrequens, Glomus sp.3 and Scutellospora sp. were found only in the organically managed crop. S. gregaria was found only in the conventional crop. Organically managed vineyards increased mycorrhization and general soil microbial activity

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review

Links2HealthierBubs' cohort study: Protocol for a record linkage study on the safety, uptake and effectiveness of influenza and pertussis vaccines among pregnant Australian women

Introduction Pregnant women and infants are at risk of severe influenza and pertussis infection. Inactivated influenza vaccine (IIV) and diphtheria-tetanus-acellular pertussis vaccine (dTpa) are recommended during pregnancy to protect both mothers and infants. In Australia, uptake is not routinely monitored but coverage appears sub-optimal. Evidence on the safety of combined antenatal IIV and dTpa is fragmented or deficient, and there remain knowledge gaps of population-level vaccine effectiveness. We aim to establish a large, population-based, multi-jurisdictional cohort of mother-infant pairs to measure the uptake, safety and effectiveness of antenatal IIV and dTpa vaccines in three Australian jurisdictions. This is a first step toward assessing the impact of antenatal vaccination programmes in Australia, which can then inform government policy with respect to future strategies in national vaccination programmes. Methods and analysis ' Links2HealthierBubs' is an observational, population-based, retrospective cohort study established through probabilistic record linkage of administrative health data. The cohort includes births between 2012 and 2017 (∼607 605 mother-infant pairs) in jurisdictions with population-level antenatal vaccination and health outcome data (Western Australia, Queensland and the Northern Territory). Perinatal data will be the reference frame to identify the cohort. Jurisdictional vaccination registers will identify antenatal vaccination status and the gestational timing of vaccination. Information on maternal, fetal and child health outcomes will be obtained from hospitalisation and emergency department records, notifiable diseases databases, developmental anomalies databases, birth and mortality registers. Ethics and dissemination Ethical approval was obtained from the Western Australian Department of Health, Curtin University, the Menzies School of Health Research, the Royal Brisbane and Women's Hospital, and the West Australian Aboriginal Health Ethics Committees. Research findings will be disseminated in peer-reviewed journals, at scientific meetings, and may be incorporated into communication materials for public health agencies and the public

Dermatophylosis in Santa Inês sheep from Distrito Federal

Relataram-se quatro casos de dermatofilose em ovinos da raça Santa Inês, no período de um ano. Microscopicamente observaram-se filamentos na forma de "trilho de bonde" e zoósporos nos quatro casos. A tentativa do isolamento do microrganismo foi realizada por meio do método de Haalstra e em apenas um caso obteve-se sucesso, observando-se colônias de aparência lisa, formato circular, cor amarelada e hemolítica em ágar sangue. O exame direto com coloração de Gram mostrou-se um método bastante eficiente na confirmação da presença do microrganismo afetando a epiderme em razão da morfologia típica do agente.Four cases of dermatophylosis were reported in Santa Inês sheep in a study period of one year. Microscopically, septate filaments and coccoid forms zoospores were observed. Attempts to isolate the microorganisms were accomplished using Haastra's method and it was successful in only one case. Dermatophilus congolensis samples have grown on blood agar, colonies where hemolytic, small, round and pigmentation vary from yellow to orange. The gram staining method was efficient to confirm the presence of the microorganism affecting the epidermis due to typical morphology of the agent