CD103 marks a subset of human CD34(+)-derived langerin(+) dendritic cells that induce T-regulatory cells via indoleamine 2,3-dioxygenase-1.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive molecule expressed in some subsets of normal and neoplastic cells. Mature human dendritic cells (DCs) have been shown to express IDO1, but little is known about its expression and function during DC differentiation from bone marrow hematopoietic stem/progenitor cells (HSPCs). Here, we show that during in vitro differentiation along the myeloid DC lineage, CD34(+) HSPCs acquire IDO1 expression, which acts in a tolerogenic manner by inducing a population of fully functional CD4(+)CD25(+) FOXP3(+) T-regulatory cells. Phenotypically, CD1a(+)CD14(-) HPSC-derived DCs expressed IDO1, langerin, CD11b, and CD1c. Cell-sorting experiments demonstrated that IDO1 expression is found in a subset of CD1a(+)CD14(-)langerin(+) cells, expressing CD103, which is capable of inducing T-regulatory cells in an IDO1-dependent manner. In conclusion, DC differentiation from CD34(+) HSPCs results in the expression of a functionally active IDO1 protein in CD1a(+)langerin(+), CD103-expressing DCs. These data point toward IDO1 expression as part of a tolerogenic signature during DC development.

Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and pareto filters

Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the ethanol production in the fermentation of Saccharomyces cerevisiae.

Protocolo para la zonificación intraparcelaria de la viña para vendimia selectiva a partir de imágenes multiespectratrales

En este trabajo se presenta un protocolo para la zonificación intraparcelaria de la viña con la finalidad de vendimia selectiva. Se basa en la adquisición de una imagen multiespectral detallada en el momento del envero, a partir de la cual se obtiene el índice de vegetación de la diferencia normalizada (NDVI). Este índice se clasifica en áreas de vigor alto y bajo mediante un proceso de clasificación no supervisada (algoritmo ISODATA). Las zonas resultantes se generalizan y se transfieren al monitor de cosecha de una máquina vendimiadora para realizar la recolección selectiva. La uva recolectada según este protocolo en parcelas control ha mostrado diferenciación en cuanto a parámetros de calidad como el pH, la acidez total, el contenido de polifenoles y el color. La imagen multiespectral utilizada fue adquirida por el satélite Quickbird-2. Los datos de calidad de la uva fueron muestreados según una malla regular de 5 filas por 10 cepas, procediendo a un test estadístico de rangos múltiples para analizar la separación de medias de las variables analizadas en cada zona de NDVI.

Prostate-targeted radiosensitization via aptamer-shRNA chimeras in human tumor xenografts

Dose-escalated radiation therapy for localized prostate cancer (PCa) has a clear therapeutic benefit; however, escalated doses may also increase injury to noncancerous tissues. Radiosensitizing agents can improve ionizing radiation (IR) potency, but without targeted delivery, these agents will also sensitize surrounding normal tissues. Here we describe the development of prostate-targeted RNAi agents that selectively sensitized prostate-specific membrane antigen–positive (PSMA-positive) cells to IR. siRNA library screens identified DNA-activated protein kinase, catalytic polypeptide (DNAPK) as an ideal radiosensitization target. DNAPK shRNAs, delivered by PSMA-targeting RNA aptamers, selectively reduced DNAPK in PCa cells, xenografts, and human prostate tissues. Aptamer-targeted DNAPK shRNAs, combined with IR, dramatically and specifically enhanced PSMA-positive tumor response to IR. These findings support aptamer-shRNA chimeras as selective sensitizing agents for the improved treatment of high-risk localized PCa.

Data triangulation in the context of opioids monitoring via wastewater analyses.

BACKGROUND: The need to contextualise wastewater-based figures about illicit drug consumption by comparing them with other indicators has been stressed by numerous studies. The objective of the present study was to further investigate the possibility of combining wastewater data to conventional statistics to assess the reliability of the former method and obtain a more balanced picture of illicit drug consumption in the investigated area. METHODS: Wastewater samples were collected between October 2013 and July 2014 in the metropolitan area of Lausanne (226,000 inhabitants), Switzerland. Methadone, its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), the exclusive metabolite of heroin, 6-monoacetylmorphine (6-MAM), and morphine loads were used to estimate the amounts of methadone and heroin consumed. RESULTS: Methadone consumption estimated from EDDP was in agreement with the expectations. Heroin estimates based on 6-MAM loads were inconsistent. Estimates obtained from morphine loads, combined to prescription/sales data, were in agreement with figures derived from syringe distribution data and general population surveys. CONCLUSIONS: The results obtained for methadone allowed assessing the reliability of the selected sampling strategy, supporting its ability to capture the consumption of a small cohort (i.e., 743 patients). Using morphine as marker, in combination with prescription/sales data, estimates in accordance with other indicators about heroin use were obtained. Combining different sources of data allowed strengthening the results and suggested that the different indicators (i.e., administration route, average dosage and number of consumers) contribute to depict a realistic representation of the phenomenon in the investigated area. Heroin consumption was estimated to approximately 13gday(-1) (118gday(-1) at street level).

Distribuição da biomassa e minerais em "família" de bananeira 'prata-anã' adubada com zinco via broto desbastado

O Norte de Minas Gerais cultiva basicamente bananeira 'Prata-Anã', cultivar especialmente exigente em zinco. A possibilidade de fornecimento de Zn, sem que esse entre em contato com o solo, é importante para a região, uma vez que vários fatores levam à baixa disponibilidade do elemento fornecido via solo, como: elevado teor de matéria orgânica na camada superficial (resultante de resíduos culturais); manutenção de elevado pH do solo - acima de 6,00 - como estratégia contrária à proliferação do agente causal do mal- do-panamá; adubações frequentes com potássio e magnésio, que além de basificar o meio, diminuem a participação do Zn no equilíbrio cátion-ânion do solo, dificultando a absorção deste micronutriente pela planta. Para determinar a distribuição de biomassa e minerais na bananeira Prata-Anã, cultivada sob irrigação no norte de Minas Gerais, quando o zinco é fornecido via broto desbastado, foi conduzido um experimento no Perímetro Irrigado de Jaíba. As plantas foram adubadas com 0,00; 1,66 e 3,33 g.família-1 de Zn (0; 25 e 50 g.família-1.ano-1 de sulfato de Zn), via muda desbastada. Um mês após as adubações de outubro de 2007 e junho de 2008, avaliaram-se a produção de massa fresca (MF) e massa seca (MS), os teores e conteúdos de minerais em todos os órgãos de uma ''família'' de bananeira composta por planta-mãe com cacho + planta-filha alta + planta-neta. As doses de Zn não influíram na produção de MF e MS das plantas na primeira avaliação, enquanto na segunda avaliação observou-se efeito positivo do tratamento apenas para MF acumulada nas folhas inferiores, nas porções do terço médio e inferior do pseudocaule, e no rizoma da planta-mãe. Tanto o teor quanto o acúmulo de nutrientes nas plantas-mãe apresentaram a seguinte ordem decrescente: K > N > Ca > Mg > P > S > Fe > Zn > B > Cu. Os teores de Zn foram afetados pela dose desse micronutriente na maioria das situações estudadas. O Zn fornecido via broto desbastado ascendeu na planta-mãe, e daí se redistribuiu na ''família'' da bananeira.

Avaliação da influência de substâncias fenólicas e carotenoides na anomalia do epicarpo da goiaba, "anelamento"

A anomalia do epicarpo da goiaba, comumente relatada por agricultores e técnicos como o "anelamento juvenil da goiaba", tem causado preocupação devido à desinformação sobre o assunto. O objetivo deste estudo foi analisar quimicamente as concentrações de substâncias fenólicas e carotenoides na região do epicarpo de goiabas afetadas pelo "anelamento", visando a caracterizar essa anomalia previamente relatada. Foram analisadas substâncias fenólicas (taninos, flavonas/flavonóis, antocianinas e fenóis totais) e carotenoides em epicarpos de frutos verdes e maduros de goiabeiras cv. Paluma, com e sem anomalia. O delineamento experimental adotado foi o inteiramente casualizado, sendo estabelecidos seis tratamentos com o epicarpo dos frutos maduro sem anomalia na região inferior (FMSI); frutos maduros sem injuria na região superior (FMSS); frutos verdes sem anomalia na região inferior (FVSI); frutos verdes sem anomalia na região superior (FVSS); frutos verdes com anomalia na região inferior (FVCI); frutos verdes com anomalia na região superior (FVCS). Dentre as substâncias analisadas, os carotenoides, os taninos e os fenóis totais mostram indicativos para a caracterização do anelamento. Tanto substâncias fenólicas quanto carotenoides apresentam propriedades antioxidantes e, dessa forma, poderiam estar relacionadas à defesa antioxidante causada por um fator de estresse ainda desconhecido, que promove o "anelamento" característico apresentado pelas goiabas.

Avaliação da diversidade genética em acessos de Psidum spp. via marcadores RAPD

O objetivo do presente trabalho foi avaliar a diversidade genética entre 20 acessos de Psidium spp. (UENF 1830 a UENF 1849, UENF- Universidade Estadual do Norte Fluminense) por marcadores RAPD. Vinte e oito primers foram utilizados, gerando um total de 157 bandas. Os marcadores moleculares RAPD foram capazes de revelar a existência de diversidade entre os 20 acessos de Psidium. Para a interpretação dos dados, o índice Nei e Li foi utilizado. Com base na análise do agrupamento hierárquico UPGMA e o método de otimização Tocher, essa diversidade pôde ser observada pela presença de acessos similares e divergentes

Cubrición parcial - Gran Via Barcelona

Partiendo de la base del proyecto: Remodelación de Gran Via de les Corts Catalanes en Barcelona, entre Plaça de les Glòries y Carrer Extremadura, el trabajo es un estudio de adecuación constructiva que propone una alternativa para la cubrición parcial de la Gran Vía, losa maciza en el proyecto original, por otra con losas ortotrópicas, sistema semiprefabricado pretensado. Consistirá en el estudio comparativo de las dos alternativas (isotrópica y ortotrópica), su cálculo mediante programa informático y el análisis y verificación general de las estructuras de barras y elementos finitos, señalando las principales diferencias encontradas y justificando la opción escogida según la ejecución de la obra, el estado de mediciones y el presupuesto. El pliego de condiciones incluido tiene como objeto principal la enumeración y el detalle de las condiciones de tipo técnico de control y ejecución que han ceñir la construcción de cada una de las alternativas

Educació moral: la via (no només) aristotèlica

Quin és el plantejament essencial que Aristòtil fa de l"educació moral? Podem dir que manté la seva eventual vigència històrica, si més no com a proposta? Es tracta d"un plantejament isolat, o podem trobar-ne epígons (més enllà de la inspiració més o menys aristotèlica que aquests tinguin)? El text que segueix pretén donar una resposta esquemàtica a les anteriors preguntes, i, de retruc, plantejar un repte conceptual (i, al capdavall, també pràctic) a tots aquells que puguin desqualificar la proposta aristotèlica per considerar-la corruptora dels principis liberals.

Parkinson"s disease DJ-1 L166P alters rRNA biogenesis by exclusion of TTRAP from the nucleolus and sequestration into cytoplasmic aggregates via TRAF6

Mutations in PARK7/DJ-1 gene are associated to autosomal recessive early onset forms of Parkinson"s disease (PD). Although large gene deletions have been linked to a loss-of-function phenotype, the pathogenic mechanism of missense mutations is less clear. The L166P mutation causes misfolding of DJ-1 protein and its degradation. L166P protein may also accumulate into insoluble cytoplasmic aggregates with a mechanism facilitated by the E3 ligase TNF receptor associated factor 6 (TRAF6). Upon proteasome impairment L166P activates the JNK/p38 MAPK apoptotic pathway by its interaction with TRAF and TNF Receptor Associated Protein (TTRAP). When proteasome activity is blocked in the presence of wild-type DJ-1, TTRAP forms aggregates that are localized to the cytoplasm or associated to nucleolar cavities, where it is required for a correct rRNA biogenesis. In this study we show that in post-mortem brains of sporadic PD patients TTRAP is associated to the nucleolus and to Lewy Bodies, cytoplasmic aggregates considered the hallmark of the disease. In SH-SY5Y neuroblastoma cells, misfolded mutant DJ-1 L166P alters rRNA biogenesis inhibiting TTRAP localization to the nucleolus and enhancing its recruitment into cytoplasmic aggregates with a mechanism that depends in part on TRAF6 activity. This work suggests that TTRAP plays a role in the molecular mechanisms of both sporadic and familial PD. Furthermore, it unveils the existence of an interplay between cytoplasmic and nucleolar aggregates that impacts rRNA biogenesis and involves TRAF6

Irrigação e adubação potássica via fertirrigação em bananeira 'willians': produção e qualidade de frutos

A aplicação de nutrientes via água de irrigação aumenta sua eficiência de utilização pelas plantas. O objetivo deste trabalho foi avaliar o efeito da adubação potássica e da irrigação na produtividade e qualidade de frutos de bananeiras, cv. Willians, na região do Médio Paranapanema, São Paulo. Foram avaliados quatro regimes hídricos: sequeiro; 0,7 da evapotranspiração de referência (ETo); 1,4 ETo, e 2,1 ETo, combinados com quatro doses de potássio (K): 0; 300; 600 e 900 kg ha.ano-1 de K2O, aplicados semanalmente via fertirrigação. Sob sequeiro, a adubação potássica foi aplicada durante o período chuvoso, parcelada em quatro vezes. Observou-se que a adubação potássica realizada via fertirrigação interfere positivamente tanto na produção como na qualidade dos frutos de bananeiras cv. Willians. Além disso, a fertirrigação favorece maior eficiência da adubação potássica quando comparada à adubação sob sequeiro.

The embryonic blood-CSF barrier has molecular elements for specific glucose transport and for the general transport of molecules via transcellular routes.

In vertebrates, early brain development takes place at the expanded anterior end of the neural tube, which is filled with embryonic cerebrospinal fluid (E-CSF). We have recently identified a transient blood-CSF barrier that forms between embryonic days E3 and E4 in chick embryos and that is responsible for the transport of proteins and control of E-CSF homeostasis, including osmolarity. Here we examined the presence of glucose transporter GLUT-1 as well the presence of caveolae-structural protein Caveolin1 (CAV-1) in the embryonic blood-CSF barrier which may be involved in the transport of glucose and of proteins, water and ions respectively across the neuroectoderm. In this paper we demonstrate the presence of GLUT-1 and CAV-1 in endothelial cells of blood vessels as well as in adjacent neuroectodermal cells, located in the embryonic blood-CSF barrier. In blood vessels, these proteins were detected as early as E4 in chick embryos and E12.7 in rat embryos, i.e. the point at which the embryonic blood-CSF barrier acquires this function. In the neuroectoderm of the embryonic blood-CSF barrier, GLUT-1 was also detected at E4 and E12.7 respectively, and CAV-1 was detected shortly thereafter in both experimental models. These experiments contribute to delineating the extent to which the blood-CSF embryonic barrier controls E-CSF composition and homeostasis during early stages of brain development in avians and mammals. Our results suggest the regulation of glucose transport to the E-CSF by means of GLUT-1 and also suggest a mechanism by which proteins are transported via transcellular routes across the neuroectoderm, thus reinforcing the crucial role of E-CSF in brain development.

Aortic blood pressure measured via EIT: investigation of different measurement settings.

Electrical impedance tomography (EIT) allows the measurement of intra-thoracic impedance changes related to cardiovascular activity. As a safe and low-cost imaging modality, EIT is an appealing candidate for non-invasive and continuous haemodynamic monitoring. EIT has recently been shown to allow the assessment of aortic blood pressure via the estimation of the aortic pulse arrival time (PAT). However, finding the aortic signal within EIT image sequences is a challenging task: the signal has a small amplitude and is difficult to locate due to the small size of the aorta and the inherent low spatial resolution of EIT. In order to most reliably detect the aortic signal, our objective was to understand the effect of EIT measurement settings (electrode belt placement, reconstruction algorithm). This paper investigates the influence of three transversal belt placements and two commonly-used difference reconstruction algorithms (Gauss-Newton and GREIT) on the measurement of aortic signals in view of aortic blood pressure estimation via EIT. A magnetic resonance imaging based three-dimensional finite element model of the haemodynamic bio-impedance properties of the human thorax was created. Two simulation experiments were performed with the aim to (1) evaluate the timing error in aortic PAT estimation and (2) quantify the strength of the aortic signal in each pixel of the EIT image sequences. Both experiments reveal better performance for images reconstructed with Gauss-Newton (with a noise figure of 0.5 or above) and a belt placement at the height of the heart or higher. According to the noise-free scenarios simulated, the uncertainty in the analysis of the aortic EIT signal is expected to induce blood pressure errors of at least ± 1.4 mmHg.

Análise de distância genética entre acessos do gênero Psidium via marcadores ISSR

O objetivo deste trabalho foi avaliar a distância genética entre 37 acessos da espécie cultivada Psidium guajava, L. (goiaba) e de araçás do gênero Psidium do banco de germoplasma da Universidade Estadual do Norte Fluminense (UENF), via marcadores moleculares ISSR. Nos 17 marcadores selecionados, foram obtidas 216 bandas polimórficas. Pelo método de agrupamento UPGMA, houve a formação de cinco principais grupos. Os acessos de araçá da espécie P. cattleyanum Sabine , ficaram alocados nos grupos I e II. No grupo II, foi observada, dentro da espécie P cattleyanum, maior proximidade com a goiabeira. No grupo III, ficou alocado o acesso da espécie P. guineense Sw (araçá-do-campo) e dentre os araçás, foi o que ficou mais próximo da goiaba. Os genótipos de goiabeira ficaram alocados do grupo IV e V, confirmando sua alta divergência. Os marcadores moleculares foram eficientes em estimar a distância genética intra e interespecífica.