Multilocus assessment of phylogenetic relationships in Alytes (Anura, Alytidae)

With the advent of large multilocus datasets, molecular systematics is experiencing very rapid progress, but important challenges remain regarding data analysis and interpretation. Midwife toads (genus Alytes) exemplify two of the most widespread problems for accurate phylogenetic reconstruction: discerning the causes of discordance between gene trees, and resolving short internodes produced during rapid, successive splitting events. The three species in subgenus Baleaphryne ( A. maurus, A. dickhilleni and A. muletensis), the sister group to A. obstetricans, have disjunct and highly restricted geographical ranges, which are thought to result from old vicariant events affecting their common ancestor, but their phylogenetic relationships are still unresolved. In this study we re-address the phylogeny of Alytes with a special focus on the relationships in Baleaphryne with a multilocus dataset including > 9000 base pairs of mitochondrial DNA and four nuclear markers (3142. bp) in all recognized taxa, including all subspecies of A. obstetricans. Both concatenation and species tree analyses suggest that A. muletensis, endemic to the Balearic island of Mallorca, is the sister taxon to a clade comprising the southeastern Iberian endemic A. dickhilleni and the North African A. maurus. This scenario is consistent with palaeogeological evidence associated with the fragmentation of the Betic-Rifean Massif, followed by the opening of the Strait of Gibraltar. On the other hand, analyses of intraspecific variation in A. obstetricans are inconclusive regarding relationships between major clades and conflict with current subspecific taxonomy.This work was supported through Project “Genomics and Evolutionary Biology” cofinanced by North Portugal Regional Operational Programme 2007/2013 (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF); the Program Operacional Factores de Competitividade (COMPETE), and by national funds from Fundação para a Ciência e a Tecnologia (FCT), through the research Project PTDC/BIA-BEC/099915/2008 to HG; and partial funds provided by grants CGL2008-04271-C02-01/BOS and CGL2011-28300 (Ministerio de Ciencia e Innovación, Ministerio de Economía y Competitividad, Spain, and FEDER) and PPII10-0097- 4200 (Junta de Comunidades de Castilla la Mancha and FEDER) to IMS, who is currently funded by Project “Biodiversity, Ecology and Global Change”, co-financed by North Portugal Regional Operational Programme 2007/2013 (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF). BMC is supported by a PhD grant from FCT (SFRH/BD/60305/2009), and HG is supported by a postdoctoral grant from FCT (SFRH/BPD/26555/2006).Peer Reviewe

A semiautomated microfluidic platform for real-time investigation of nanoparticles' cellular uptake and cancer cells' tracking

Aims: develop a platform composed of labeled dendrimer nanoparticles and a microfluidic device for real-time monitoring of cancer cells fate. Materials and Methods: The physicochemical and biological characterization of the developed Carboxymethyl-chitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles were performed using TEM, AFM, Zeta Sizer, DSC and cytotoxicity screening. Cancer cell lines derived from different tumor types, including HeLa (Cervical Carcinoma), HCT-116 (Colon Carcinoma) and U87MG (Glioblastoma), were exposed to different concentrations of CMCht/PAMAM dendrimer nanoparticles over a period of 3 days (MTS/DNA). Results: Nanoparticles were successfully modified with an average size of 50 nm. Internalization levels go from 87% to 100% in static and from 95% to 100% in dynamic conditions. Viability levels range from 95% to 100% in static and from 90% to 100% in dynamic conditions, being HCT the most sensitive to the presence of the NP. Conclusions: the results show different responses to the presence of 0.5 mg.mL-1 dendrimer nanoparticles when comparing static to dynamic conditions, with a tendency towards higher sensitivity when subjected to confinement. This work demonstrated that the proposed microfluidic-based platform allows real-time cell monitoring, which, upon more studies, namely the assessment of the drug release effect, could be used for cancer theranostics.FR Maia acknowledges ERC-2012-ADG 20120216–321266 (ComplexiTE) for her Postdoc scholarship. JM Oliveira thanks Portuguese Foundation for Science and Technology (FCT) for his distinction attributed under the FCT Investigator program (IF/00423/2012). BM Costa also thanks Portuguese Foundation for Science and Technology (PTDC/SAU-GMG/113795/2009 and IF/00601/2012 to BM Costa), Fundação Calouste Gulbenkian (BM Costa) and Liga Portuguesa Contra o Cancro (BM Costa). MR Carvalho also thanks the funding through the LA ICVS/3Bs project (UID/Multi/50026/2013). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.info:eu-repo/semantics/publishedVersio

Multilocus phylogeography of the common midwife toad, Alytes obstetricans (Anura, Alytidae): Contrasting patterns of lineage diversification and genetic structure in the Iberian refugium

Recent investigations on the evolutionary history of the common midwife toad (Alytes obstetricans) revealed high levels of geographically structured genetic diversity but also a situation where delineation of major historical lineages and resolution of their relationships are much more complex than previously thought. We studied sequence variation in one mitochondrial and four nuclear genes throughout the entire distribution range of all recognized A. obstetricans subspecies to infer the evolutionary processes that shaped current patterns of genetic diversity and population subdivision. We found six divergent, geographically structured mtDNA haplogroups diagnosing population lineages, and varying levels of admixture in nuclear markers. Given the timeframe inferred for the splits between major lineages, the climatic and environmental changes that occurred during the Pleistocene seem to have shaped the diversification history of A. obstetricans. Survival of populations in allopatric refugia through the Ice Ages supports the generality of the >refugia-within-refugia> scenario for the Iberian Peninsula. However, lineages corresponding to subspecies A. o. almogavarii, A. o. pertinax, A. o. obstetricans, and A. o. boscai responded differently to Pleistocene climatic oscillations after diverging from a common ancestor. Alytes o. obstetricans expanded northward from a northern Iberian refugium through the western Pyrenees, leaving a signal of contrasting patterns of genetic diversity, with a single mtDNA haplotype north of the Pyrenees from SW France to Germany. Both A. o. pertinax and A. o. boscai are widespread and genetically diverse in Iberia, the latter comprising two divergent lineages with a long independent history. Finally, A. o. almogavarii is mostly restricted to the north-eastern corner of Iberia north of the Ebro river, with additional populations in a small region in south-eastern France. This taxon exhibits unparalleled levels of genetic diversity and little haplotype sharing with other lineages, suggesting a process of incipient speciation.This work was supported through Project “Genomics and Evolutionary Biology” co-financed by North Portugal Regional Operational Programme 2007/2013 (ON. 2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF); by FEDER funds through the Operational Programme for Competitiveness Factors – COMPETE and by National Funds through FCT – Foundation for Science and TechnologyPTDC/BIA-BEC/099915/2008 and FCOMP-01-0124-FEDER-008915 to HG; and by partial funds provided by Grants CGL2008-04271-C02-01/BOS and CGL2011-28300 (Ministerio de Ciencia e Innovación, Ministerio de Economía y Competitividad, Spain, and FEDER) and PPII10-0097-4200 (Junta de Comunidades de Castilla la Mancha and FEDER) to IMS. IMS was funded by Project “Biodiversity, Ecology and Global Change”, co-financed by ON. 2–O Novo Norte, under the NSRF, through the ERDF, and is currently supported by funding from the Spanish Severo Ochoa Program (SEV-2012-0262). HG was supported by a postdoctoral Grant from FCT (SFRH/BPD/26555/2006) and by funding from the Projecto Incentivo (INCENTIVO/BIA/LA0027/2013), and is currently supported by a postdoctoral Grant from FCT (SFRH/BPD/102966/2014). BMC was supported by a PhD Grant from FCT (SFRH/BD/60305/2009). FS is supported by a postdoctoral Grant from FCT (SFRH/BPD/87721/2012) and TSN by a research Grant (BI) from ICETA/UP.Peer Reviewe

Characterization of the Antidiabetic Role of Parkinsonia aculeata (Caesalpineaceae)

This paper reports the characterization of the antidiabetic role of a hydroethanolic extract from Parkinsonia aerial parts (HEPA), in normal and alloxan-induced diabetic rats, treated with HEPA (125 and 250 mg/kg; p.o.). Oral glucose tolerance test, acute oral toxicity test and preliminary phytochemical analyses were performed. The diabetic rats treated with HEPA showed a significant reduction in serum and urinary glucose, urinary urea and triglyceride levels, as compared to the diabetic untreated group. However, in the normal treated groups, a significant reduction was found only in serum triglyceride levels. In all treated diabetic groups, an improvement in hepatic glycogen was observed, as well as a decrease in liquid intake and urinary volume, and an enhancement in the weight of skeletal muscles (soleus and extensor digitorum longus), kidneys and epididymal adipose tissue. Nevertheless, body and liver weights were ameliorated only in the diabetic group treated with HEPA (250 mg/kg). Moreover, oral glucose tolerance was higher in animals treated with HEPA, while results also showed that HEPA could be considered toxicologically safe. Phytochemical analysis revealed the presence of tanins, flavonoids and steroids in HEPA. In conclusion, P. aculeata presents an antidiabetic activity and other beneficial effects that ameliorate diabetes and associated complications

IgG+ Extracellular Vesicles Measure Therapeutic Response in Advanced Pancreatic Cancer

Funding Information: J.E. was supported by grant 765492 from H2020-MSCA-ITN-2017. J.M. was supported by “Fundação para a Ciência e a Tecnologia” (PD/BD/105866/2014). S.B. was supported by the EMBO Installation Grant 3921. This work was supported by the Champalimaud Foundation and grant LCF/PR/HR19/52160014 from “La Caixa” Foundation. M.O.’s research is partially supported by National Funds through FCT, Fundação para a Ciência e a Tecnologia, projects 343 UIDB/04674/2020 (CIMA) and H2020-MSCA-RISE-2020/101007950, with the title ”DecisionES—Decision Support for the Supply of Ecosystem Services under Global Change,” funded by the Marie Curie International Staff Exchange Scheme.(1) Background: Pancreatic ductal adenocarcinoma (PDAC) is expected to be the second-leading cause of cancer deaths by 2030. Imaging techniques are the standard for monitoring the therapy response in PDAC, but these techniques have considerable limits, including delayed disease progression detection and difficulty in distinguishing benign from malignant lesions. Extracellular vesicle (EV) liquid biopsy is an emerging diagnosis modality. Nonetheless, the majority of research for EV-based diagnosis relies on point analyses of EVs at specified times, while longitudinal EV population studies before and during therapeutic interventions remain largely unexplored. (2) Methods: We analyzed plasma EV protein composition at diagnosis and throughout PDAC therapy. (3) Results: We found that IgG is linked with the diagnosis of PDAC and the patient’s response to therapy, and that the IgG+ EV population increases with disease progression and reduces with treatment response. Importantly, this covers PDAC patients devoid of the standard PDAC seric marker CA19.9 expression. We also observed that IgG is bound to EVs via the tumor antigen MAGE B1, and that this is independent of the patient’s inflammatory condition and IgG seric levels. (4) Conclusions: We here propose that a population analysis of IgG+ EVs in PDAC plasma represents a novel method to supplement the monitoring of the PDAC treatment response.publishersversionpublishe

Transcriptome Reprogramming of CD11b(+) Bone Marrow Cells by Pancreatic Cancer Extracellular Vesicles

Funding: JM was supported by “Fundação para a Ciência e a Tecnologia” (PD/BD/105866/2014). This work was supported by the Champalimaud Foundation; grant 751547 from H2020-MSCAIF-2016; EMBO Installation Grant 3921; grant 2017NovPCC1058 from Breast Cancer Now’s Catalyst Programme, which is supported by funding from Pfizer; grant 765492 from H2020-MSCA-ITN-2017; and grant LCF/PR/HR19/52160014 from “La Caixa” Foundation. This work was also funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE and National Funds through the Foundation for Science and Technology (FCT), under the project: PTDC/MED-ONC/28489/2017 (to AM). JP acknowledges the FCT grant SFRH/BD/137319/2018.publishersversionpublishe

O futuro do direito administrativo: estudos em homenagem ao prof. Edilson Nobre

Divulgação dos SUMÁRIOS das obras recentemente incorporadas ao acervo da Biblioteca Ministro Oscar Saraiva do STJ. Em respeito à Lei de Direitos Autorais, não disponibilizamos a obra na íntegra.Localização na estante: 35(81) F996dCoordenado por: Bianor Arruda Bezerra Neto, Leonardo Henrique de Cavalcante Carvalho, Marco Bruno de Miranda Clementino e Robson Maia Lin

DIABETES MELLITUS: RISCO POTENCIAL PARA LESÕES VASCULARES E MORTE

Diabetes mellitus é um conjunto de alterações metabólicas que tem como característica principal a hiperglicemia, sendo uma síndrome metabólica grave que leva a varias disfunções e quando não tratada causa insuficiência de vários órgãos, principalmente olhos, rins, nervos, cérebro e comprometendo também a integridade morfofuncional do endotélio vascular