Different ability of multidrug-resistant and-sensitive counterpart cells to release and capture extracellular vesicles

Cancer multidrug resistance (MDR) is one of the main challenges for cancer treatment efficacy. MDR is a phenomenon by which tumor cells become resistant to several unrelated drugs. Some studies have previously described the important role of extracellular vesicles (EVs) in the dissemination of a MDR phenotype. EVs’ cargo may include different players of MDR, such as microRNAS and drug-efflux pumps, which may be transferred from donor MDR cells to recipient drug-sensitive counterparts. The present work aimed to: (i) compare the ability of drug-sensitive and their MDR counterpart cells to release and capture EVs and (ii) study and relate those differences with possible distinct fate of the endocytic pathway in these counterpart cells. Our results showed that MDR cells released more EVs than their drug-sensitive counterparts and also that the drug-sensitive cells captured more EVs than their MDR counterparts. This difference in the release and capture of EVs may be associated with differences in the endocytic pathway between drug-sensitive and MDR cells. Importantly, manipulation of the recycling pathway influenced the response of drug-sensitive cells to doxorubicin treatment.This article is a result of 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). We thank Spanish MINECO (SAF2015-66312 to JMF) and for the REDIEX (Spanish Excellence Network in Exosomes) and the Severo Ochoa Excellence Accreditation (SEV-2016-0644). The authors thank the Portuguese Foundation for Science and Technology (FCT) for the PhD grant of DS (SFRH/BD/98054/2013). Cristina P.R. Xavier is supported by FCT and Fundo Social Europeu (FSE), through the post-doc grant SFRH/BPD/122871/2016. The authors also acknowledge the European COST Action-European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD, BM1202) for short-term mission fellowship (ECOST-STSM-BM1202-150317-083396) and Grupo Español de investigacion en Vesiculas Extracelulares for GEIVEX mobility fellowship which allowed the work of DS in CICbioGUNE

Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant

Introduction: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor (MAX) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals. Case presentation: The first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene. Conclusion: This case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk

Some arachnidan peptides with potential medical application

The search for new active drugs that can alleviate or cure different diseases is a constant challenge to researchers in the biological area and to the pharmaceutical industry. Historically, research has focused on the study of substances from plants. More recently, however, animal venoms have been attracting attention and studies have been successful in addressing treatment of accidents. Furthermore, venoms and their toxins have been considered good tools for prospecting for new active drugs or models for new therapeutic drugs. In this review, we discuss some possibilities of using different toxins, especially those from arachnid venoms, which have shown some potential application in diseases involving pain, hypertension, epilepsy and erectile dysfunction. A new generation of drugs is likely to emerge from peptides, including those found in animal venoms

Two new species of Phalangopsis Serville, 1831 (Orthoptera: Grylloidea: Phalangopsidae) from Brazilian Amazon Forest

We describe here two new species of the genus Phalangopsis Serville, 1831 from the Brazilian Amazon Forest. The male genitalia and the female copulatory papilla were described, and a combination of diagnostic characteristics was given to separate both new species from the other described species. The principal morphological characteristics of this genus were discussed.Aqui foram descritas duas espécies novas do gênero Phalangopsis Serville, 1831 da Floresta Amazônica brasileira. A genitália masculina e a papila copulatória feminina são descritas, bem como uma combinação de características diagnósticas para separar ambas as novas espécies das outras espécies descritas. As principais características morfológicas foram discutidas

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Conservation of geosites as a tool to protect geoheritage: the inventory of Ceará Central Domain, Borborema Province - NE/Brazil

The Ceará Central Domain, in the northern Borborema Province/NE Brazil, encompasses important geological records (geosites) which allow understanding a relevant period of the Earth’s evolution, mainly associated to Neoproterozoic Brazilian/Pan-African Cycle and West Gondwana amalgamation, besides Neoarchean to Ordovician records. The presented geoheritage inventory aims to characterise the geosites with scienti c relevance of Ceará Central Domain. By applying a method for large areas, the nal selection resulted in eight geological frameworks represented by 52 geosites documented in a single database. This is the rst step for a geoconservation strategy based on systematic inventories, statutory protection, geoethical behaviour and awareness about scienti c, educational and/or cultural relevance of geosites.We specially thank all experts that helped us with this inventory: Afonso Almeida, Carlos E.G. de Araújo, César Veríssimo, Christiano Magini, Clóvis Vaz Parente, Felipe G. Costa, Irani C. Mattos, Neivaldo de Castro, Otaciel de Melo, Sebástian G. Chiozza, Ticiano Santos and Stefano Zincone. We are also thankful to Kátia Mansur, Ricardo Fraga Pereira and anonymous reviewers for their valuable contributions. PM is grateful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for PhD mobility scholarship PDSE Program/Process n 88881.132168/2016-01info:eu-repo/semantics/publishedVersio