Application of gold nanoparticles as radiosensitizer for metastatic prostate cancer cell lines

More than 50% of all prostate cancer (PCa) patients are treated by radiotherapy (RT). Radioresistance and cancer recurrence are two consequences of the therapy and are related to dose heterogeneity and non-selectivity between normal and tumoral cells. Gold nanoparticles (AuNPs) could be used as potential radiosensitizers to overcome these therapeutic limitations of RT. This study assessed the biological interaction of different morphologies of AuNPs with ionizing radiation (IR) in PCa cells. To achieve that aim, three different amine-pegylated AuNPs were synthesized with distinct sizes and shapes (spherical, AuNPsp-PEG, star, AuNPst-PEG, and rods, AuNPr-PEG) and viability, injury and colony assays were used to analyze their biological effect on PCa cells (PC3, DU145, and LNCaP) when submitted to the accumulative fraction of RT. The combinatory effect of AuNPs with IR decreased cell viability and increased apoptosis compared to cells treated only with IR or untreated cells. Additionally, our results showed an increase in the sensitization enhancement ratio by cells treated with AuNPs and IR, and this effect is cell line dependent. Our findings support that the design of AuNPs modulated their cellular behavior and suggested that AuNPs could improve the RT efficacy in PCa cells.The author is grateful for the financial support of Foundation for Science and Technology (grant reference: SFRH/BD/138271/2018).info:eu-repo/semantics/publishedVersio

Constraining New Physics with the CDF Measurement of CP Violation in B→ψKSB \to \psi K_S

Recently, the CDF collaboration has reported a measurement of the CP asymmetry in the $B\to\psi K_S$ decay: $a_{\psi K_S}=0.79^{+0.41}_{-0.44}$. We analyze the constraints that follow from this measurement on the size and the phase of contributions from new physics to B-\barB mixing. Defining the relative phase between the full $M_{12}$ amplitude and the Standard Model contribution to be $2\theta_d$, we find a new bound: \sin2\theta_d\gsim-0.6 (-0.87) at one sigma (95% CL). Further implications for the CP asymmetry in semileptonic B decays are discussed.Comment: 13 pages, harvmac, 3 figures; v2: a discussion of new physics effects on tree level decays added; references added; accepted for publication in Physical Review Letter

Evaluation of the indicators of inflammation in the diagnosis of ovine mastitis

O objetivo do presente trabalho foi avaliar diferentes indicadores inflamatórios no diagnóstico da mamite em ovinos da raça Santa Inês. Após a realização do exame físico das mamas e a prova de fundo escuro, foram coletadas e analisadas 390 amostras de leite, sendo as metades mamárias divididas de acordo com o exame bacteriológico e a prova de fundo escuro, resultando em 290 amostras negativas em ambos os exames, 90 amostras negativas à prova de fundo escuro e positivas na cultura bacteriológica, 5 amostras positivas à prova de fundo escuro e negativas ao exame bacteriológico e 3 amostras positivas em ambos os testes. Nestas amostras foram realizadas a contagem automática de células somáticas (CCS), o California Mastitis Test (CMT), a determinação da concentração hidrogeniônica (pH) e dos teores de cloreto e lactose, e ainda a avaliação do índice de cloreto-lactose. Os maiores valores preditivos foram observados para a CCS, CMT e teor de cloreto; o pH, o teor de lactose e o índice cloreto-lactose apresentaram-se como marcadores inflamatórios menos sensíveis, onde se considerou o resultado da cultura bacteriológica como padrão ouro. O exame físico não se mostrou como método diagnóstico seguro quando utilizado isoladamente, exaltando a importância da associação de outros meios diagnósticos indiretosThe aim of this trial was to evaluate distinct indictors of inflammation in the diagnosis of mastitis in Santa Ines ewes. The physical examination and the dark bottom cup test were performed. Afterwards, the bacteriologic samples of 390 milk samples were analyzed. The samples were divided according to the bacteriological examination and the dark cup bottom test, resulting in 290 samples negative in both tests, 90 samples positive in the bacteriological examination and negative in the dark cup bottom test, 5 samples positive in the dark cup bottom test and negative in bacteriological culture, and 3 samples positive in both tests. The automatic somatic cell count (SSC), the California mastitis test (CMT), the pH, the chloride and lactose content, and the chloride-lactose number were established. Then, their predictive value as a indicator of inflammation was calculated assuming the bacteriologic examination as the gold standard test. The CCS, CMT and chloride content proved to be the best predictors, while the pH, the lactose content and chloride-lactose number were the least sensitive tests. The physical examination was revealed to be a nonsensitive diagnostic procedure when used as the only procedure to detect the disease, showing that other diagnostics tests are requiredFAPESPCNP

Linking plant phenology to conservation biology

Phenology has achieved a prominent position in current scenarios of global change research given its role inmonitoring and predicting the timing of recurrent life cycle events. However, the implications of phenology to environmental conservation and management remain poorly explored. Here,we present the first explicit appraisal of howphenology-amultidisciplinary science encompassing biometeorology, ecology, and evolutionary biology- can make a key contribution to contemporary conservation biology. We focus on shifts in plant phenology induced by global change, their impacts on species diversity and plant-animal interactions in the tropics, and how conservation efforts could be enhanced in relation to plant resource organization. We identify the effects of phenological changes and mismatches in the maintenance and conservation of mutualistic interactions, and examine how phenological research can contribute to evaluate, manage and mitigate the consequences of land-use change and other natural and anthropogenic disturbances, such as fire, exotic and invasive species. Wealso identify cutting-edge tools that can improve the spatial and temporal coverage of phenological monitoring, from satellites to drones and digital cameras. We highlight the role of historical information in recovering long-term phenological time series, and track climate-related shifts in tropical systems. Finally, we propose a set of measures to boost the contribution of phenology to conservation science.Weadvocate the inclusion of phenology into predictive models integrating evolutionary history to identify species groups that are either resilient or sensitive to future climate-change scenarios, and understand how phenological m ismatches can affect community dynamics, ecosystem services, and conservation over time

ECOSSISTEMA DE INOVAÇÃO PEDAGÓGICA DIGITAL

Resumo: A partir da constatação de que os elementos vida, conhecimento e cultura vem sofrendo marcantes alterações cabendo ao elemento “escola” buscar uma ressignificação de seus currículos, sob pena de não mais se comunicar eficientemente com a sociedade. O professor que se reconhece como o protagonista de sua prática e utiliza as tecnologias educacionais de modo crítico e criativo, coloca-se em sintonia com as linguagens e símbolos que fazem parte deste novo mundo do aluno, além de conferir a este maior autonomia e reponsabilidade sob seu processo de aprendizagem. O objetivo geral deste projeto foi de estruturar um conjunto de ações que despertassem e capacitassem professores e alunos a atuarem mediados por tecnologias educacionais de modo crítico e criativo, colocando-os em sintonia com as linguagens e símbolos que fazem parte deste novo mundo digital e interconectado

Detailed Clinical and Psychological Phenotype of the X-linked HNRNPH2-Related Neurodevelopmental Disorder

Objective: To expand the clinical phenotype of the X-linked HNRNPH2-related neurodevelopmental disorder in 33 individuals. Methods: Participants were diagnosed with pathogenic or likely pathogenic variants in HNRNPH2 using American College of Medical Genetics and Genomics/Association of Molecular Pathology criteria, largely identified via clinical exome sequencing. Genetic reports were reviewed. Clinical data were collected by retrospective chart review and caregiver report including standardized parent report measures. Results: We expand our clinical characterization of HNRNPH2-related disorders to include 33 individuals, aged 2-38 years, both females and males, with 11 different de novo missense variants, most within the nuclear localization signal. The major features of the phenotype include developmental delay/intellectual disability, severe language impairment, motor problems, growth, and musculoskeletal disturbances. Minor features include dysmorphic features, epilepsy, neuropsychiatric diagnoses such as autism spectrum disorder, and cortical visual impairment. Although rare, we report early stroke and premature death with this condition. Conclusions: The spectrum of X-linked HNRNPH2-related disorders continues to expand as the allelic spectrum and identification of affected males increases.Grant support for L. Boyle provided by TL1TR001875.info:eu-repo/semantics/publishedVersio

El impacto de la pandemia del Covid-19 en la actuación de la burocracia de primera línea en Brasil

O enfrentamento da pandemia de Covid-19 exige que o Estado tome decisões difíceis que perpassam a ação da burocracia que implementa políticas públicas na interação com a população, a burocracia de nível de rua (BNR). Neste artigo, baseado em estudo exploratório de método misto, analisamos como a atuação cotidiana desses burocratas em diferentes políticas públicas - saúde, assistência social, acesso à justiça, segurança pública e educação - foi alterada durante a pandemia, bem como analisamos as suas consequências. Três categorias que ilustram a dinâmica do trabalho da BNR durante a pandemia foram identificadas por análise dos sentimentos dos burocratas, mudanças no seu trabalho e na relação com a população: a BNR que enfrenta a crise na linha de frente; a BNR que sofre os efeitos da pandemia, mas cujo trabalho não demanda enfrentá-la diretamente; e a BNR cujo trabalho migrou para o formato remoto. Concluímos que, durante a pandemia, a BNR, em diferentes graus, deparou-se com um agravamento de problemas estruturais, como o seu alijamento dos processos decisórios, restritos ao alto escalão governamental, e a exacerbação de conflitos e ambiguidades já existentes.Dealing with the Covid-19 pandemic requires that the State make hard decisions that involve the action of bureaucrats who interact with the population through the implementation of public policy, the street-level bureaucracy (SLB). In this paper, based on a mixed- method exploratory study, we analyze how the daily performance of street-level bureaucrats in different policy areas- health and social care, access to the justice system, public security and education - has changed during the pandemic. We also explore the repercussions of those changes. Based on the analysis of the perceptions of bureaucrats, changes in their work and in their relationship with the public, we identify three categories that illustrate the dynamics of SLB work during the pandemic: the SLB who faces the crisis on the front lines; the SLB who suffers the effects of the pandemic, but whose work does not require her to face it directly; and the SLB who began to work remotely. We conclude that, during the pandemic, SLB suffered in varying degrees an aggravation of structural problems, such as their removal from decision-making processes - now restricted to the highest government level - and the exacerbation of already existing conflicts and ambiguities.Hacer frente a la pandemia de Covid-19 requiere que el Estado tome decisiones difíciles que van más allá de la acción de la burocracia que implementa las políticas públicas en la interacción con la población, la burocracia de primera línea (BPL). En este artículo, a partir de un estudio exploratorio de método mixto, analizamos cómo el desempeño diario de estos burócratas en diferentes políticas públicas - salud, asistencia social, acceso a la justicia, seguridad pública y educación - se modificó durante la pandemia y sus consecuencias. Se identificaron tres categorías que ilustran la dinámica del trabajo de BNR durante la pandemia, analizando los sentimientos de los burócratas, los cambios en su trabajo y en la relación con la población: la BPL que enfrenta la crisis en primera línea; la BPL que sufre los efectos de la pandemia, pero cuyo trabajo no exige enfrentarla directamente; y la BPL cuyo trabajo migró al formato remoto. Concluimos que, durante la pandemia, la BPL, en diferentes grados, enfrentó un agravamiento de problemas estructurales, como su remoción de los procesos de toma de decisiones, restringida al más alto nivel de gobierno, y la exacerbación de conflictos y ambigüedades ya existentes

Identification of Thioredoxin Glutathione Reductase Inhibitors That Kill Cestode and Trematode Parasites

Parasitic flatworms are responsible for serious infectious diseases that affect humans as well as livestock animals in vast regions of the world. Yet, the drug armamentarium available for treatment of these infections is limited: praziquantel is the single drug currently available for 200 million people infected with Schistosoma spp. and there is justified concern about emergence of drug resistance. Thioredoxin glutathione reductase (TGR) is an essential core enzyme for redox homeostasis in flatworm parasites. In this work, we searched for flatworm TGR inhibitors testing compounds belonging to various families known to inhibit thioredoxin reductase or TGR and also additional electrophilic compounds. Several furoxans and one thiadiazole potently inhibited TGRs from both classes of parasitic flatworms: cestoda (tapeworms) and trematoda (flukes), while several benzofuroxans and a quinoxaline moderately inhibited TGRs. Remarkably, five active compounds from diverse families possessed a phenylsulfonyl group, strongly suggesting that this moiety is a new pharmacophore. The most active inhibitors were further characterized and displayed slow and nearly irreversible binding to TGR. These compounds efficiently killed Echinococcus granulosus larval worms and Fasciola hepatica newly excysted juveniles in vitro at a 20 µM concentration. Our results support the concept that the redox metabolism of flatworm parasites is precarious and particularly susceptible to destabilization, show that furoxans can be used to target both flukes and tapeworms, and identified phenylsulfonyl as a new drug-hit moiety for both classes of flatworm parasites