Impact of endostatin gene therapy on myeloid-derived suppressor cells from a metastatic renal cell carcinoma

Aim: To evaluate the role of endostatin (ES) gene therapy on myeloid-derived suppressor cells (MDSC) in a metastatic model of renal cell carcinoma (RCC). Materials and Methods: Balb/C mice bearing orthotopic Renca tumors were treated with NIH/3T3LendSN or, as a control, with NIH/3T3-LXSN cells. At the end of in vivo experiment, plasma and tissue lung samples were collected. Plasma ES and granulocyte colony stimulating factor (G-CSF) levels were measured by ELISA and Milliplex, respectively. Quantification of CD11b⁺Gr⁻1⁺ cells and their subsets was performed by flow cytometry. Reactive oxygen species (ROS) production was measured in CD11b⁺Gr⁻1⁺ MDSC using the DCFDA marker by flow cytometry. Results: Metastatic RCC (mRCC) induced expansions of CD11b⁺Gr⁻1⁺ MDSC and promoted accumulation of these cells and their subtypes in lymphoid organ and metastases. ES treatment promoted low G-CSF plasmatic levels which were produced by the tumor microenvironment, reflecting the reduced metastatic accumulation of CD11b⁺Gr⁻1⁺ MDSC in the lungs. However, the therapy was selective for granulocytic cells, thus reducing the production of ROS. Conclusion: These findings confirm the expansion of MDSC during metastatic progression of RCC and indicate the important role of ES in reducing MDSC and possible use of ES therapy in combined anticancer treatment

Evidential Communities for Complex Networks

Community detection is of great importance for understand-ing graph structure in social networks. The communities in real-world networks are often overlapped, i.e. some nodes may be a member of multiple clusters. How to uncover the overlapping communities/clusters in a complex network is a general problem in data mining of network data sets. In this paper, a novel algorithm to identify overlapping communi-ties in complex networks by a combination of an evidential modularity function, a spectral mapping method and evidential c-means clustering is devised. Experimental results indicate that this detection approach can take advantage of the theory of belief functions, and preforms good both at detecting community structure and determining the appropri-ate number of clusters. Moreover, the credal partition obtained by the proposed method could give us a deeper insight into the graph structure

Combining metagenomics with morphology-based approaches to understand microbiome –meiobenthos interactions

Sediment microbiome has an essential role in regulating ecosystem functions, not only regulating primary productivity and nutrient cycling but also shaping trophic interactions with higher trophic levels. While the importance of microbiome in terrestrial soil systems is highly recognized, its role in marine aquatic environments remains much less studied. Microbiome can be highly affected by bottom up (abiotic factors) and top down (predation by meiofauna) effects. Understanding the interaction effect between abiotic and biotic factors on microbiome communities will be an essential step for future predictions of ecosystem stability. To address this knowledge gap we studied the interactions among microbiome diversity and nematode communities in highly heterogenous Sado Estuary, SW Portugal. The samples were taken from three contrasting sites with varying sediment characteristics and human impact degrees. From each site, three replicate samples for sediment characterization (total organic matter, granulometry, total C and N), microbiome (sensu lato) and nematode community were taken. Total DNA from sediment was extracted using DNeasy Power Soil kit® (MOBIO, Qiagen) and processed for Illumina MiSeq platform sequencing targeting the V3-V4 region of 16S rRNA gene. Sediment characterization indicated heterogeneity between sites with distinct levels of contamination, which resulted in contrasting microbial communities. All sites showed a high α-biodiversity with predominance of Proteobacteria phylum, particularly Woeseiaceae, Desulfobacteraceae and Rhodobacteraceae families. Beside this heterogeneity in microbiome community, β-diversity was demonstrated to be very high, greatly discriminating among all three sites. Nematode composition and abundance followed a similar pattern as microbiome highlighting influential role of sediment characteristics. Combining abiotic sediment characteristics with metagenomics and morphological identification of higher trophic level communities might certainly contribute to the understanding of complex benthic interactions in marine ecosystems

Novel Prostate Specific Antigen plastic antibody designed withcharged binding sites for an improved protein binding and itsapplication in a biosensor of potentiometric transduction

This work shows that the synthesis of protein plastic antibodies tailored with selected charged monomersaround the binding site enhances protein binding. These charged receptor sites are placed over a neutralpolymeric matrix, thus inducing a suitable orientation the protein reception to its site. This is confirmed bypreparing control materials with neutral monomers and also with non-imprinted template. This concepthas been applied here to Prostate Specific Antigen (PSA), the protein of choice for screening prostate can-cer throughout the population, with serum levels >10 ng/mL pointing out a high probability of associatedcancer.Protein Imprinted Materials with charged binding sites (C/PIM) have been produced by surfaceimprinting over graphene layers to which the protein was first covalently attached. Vinylben-zyl(trimethylammonium chloride) and vinyl benzoate were introduced as charged monomers labellingthe binding site and were allowed to self-organize around the protein. The subsequent polymerizationwas made by radical polymerization of vinylbenzene. Neutral PIM (N/PIM) prepared without orientedcharges and non imprinted materials (NIM) obtained without template were used as controls.These materials were used to develop simple and inexpensive potentiometric sensor for PSA. Theywere included as ionophores in plasticized PVC membranes, and tested over electrodes of solid or liq-uid conductive contacts, made of conductive carbon over a syringe or of inner reference solution overmicropipette tips. The electrodes with charged monomers showed a more stable and sensitive response,with an average slope of -44.2 mV/decade and a detection limit of 5.8 × 10−11mol/L (2 ng/mL). The cor-responding non-imprinted sensors showed lower sensitivity, with average slopes of -24.8 mV/decade.The best sensors were successfully applied to the analysis of serum, with recoveries ranging from 96.9to 106.1% and relative errors of 6.8%

Chitosan crosslinked with genipin as support matrix for application in food process: Support characterization and β-d-galactosidase immobilization

AbstractIn order to develop safer processes for the food industry, we prepared a chitosan support with the naturally occurring crosslinking reagent, genipin, for enzyme. As application model, it was tested for the immobilization of β-d-galactosidase from Aspergillus oryzae. Chitosan particles were obtained by precipitation followed by adsorption of the enzyme and crosslinking with genipin. The particles were characterized by Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The immobilization of the enzyme by crosslinking with genipin provided biocatalysts with satisfactory activity retention and thermal stability, comparable with the ones obtained with the traditional methodology of immobilization using glutaraldehyde. β-d-Galactosidase–chitosan–genipin particles were applied to galactooligosaccharides synthesis, evaluating the initial lactose concentration, pH and temperature, and yields of 30% were achieved. Moreover, excellent operational stability was obtained, since the immobilized enzyme maintained 100% of its initial activity after 25 batches of lactose hydrolysis. Thus, the food grade chitosan–genipin particles seem to be a good alternative for application in food process

Influência da qualidade dos materiais de reprodução na reflorestação com sobreiro

O sobreiro ocupa em Portugal cerca de 721000 ha o que corresponde a 21,5 % da área fl orestal nacional e 33% da área mundial (APCOR, 2005). A sua distribuição no território nacional traduz não só a sua adaptação a determinadas condições edafo-climaticas, mas tem sido condicionada por várias circunstancias, como o arroteamento, o fogo, o abuso do pastoreio, a exploração agrícola intensiva e as plantações fl orestais que contrariaram ou favoreceram a sua existência nesses locais (Natividade, 1950). A distribuição desta espécie é particularmente signifi cativa em zonas onde têm ocorrido acontecimentos climáticos graves e onde os níveis de desertifi cação humana são críticos. A fi leira da cortiça salienta-se por Portugal ocupar o primeiro lugar entre os países produtores, transformadores e exportadores de cortiça, correspondendo-lhe mais de metade da produção mundial desta matéria-prima. O nosso País é a origem de aproximadamente 60% das transacções de cortiça a nível mundial, valor que sobe para 80% quando nos referimos a transacções de produtos transformados. A nível nacional, o valor das exportações de cortiça representam aproximadamente 0,7% do PIB, 2,24% das exportações e correspondem a mais de 33% do conjunto das exportações de produtos fl orestais (APCOR, 2005). Para além da importância económica do sector corticeiro a nível nacional, o aumento da consciência e do interesse da sociedade nas questões ambientais, faz com que o montado de sobro seja reconhecido cada vez mais como um espaço fl orestal, de elevada biodiversidade, paisagísticamente único, que potencia micro-economias locais baseadas numa agricultura e pastorícia extensivas, interessante para outras actividades como o turismo rural e a caça. O sobreiro tem sido a espécie fl orestal que mais tem benefi ciado dos meios fi nanceiros disponibilizados aos proprietários fl orestais para a refl orestação no âmbito da aplicação das medidas de reforma da Política Agrícola Comum da UE, na arborização das terras agrícolas. Contudo, têm-se registado com frequência elevadas taxas de insucesso na arborização sendo a qualidade dos materiais florestais de reprodução (MFR) apontada como uma das causas. Neste trabalho abordaremos a a qualidade dos materiais de reprodução, considerando-a do ponto de vista genético e fisiológicoN/

Conduction channels of superconducting quantum point contacts

Atomic quantum point contacts accommodate a small number of conduction channels. Their number N and transmission coefficients {T_n} can be determined by analyzing the subgap structure due to multiple Andreev reflections in the current-voltage (IV) characteristics in the superconducting state. With the help of mechanically controllable break-junctions we have produced Al contacts consisting of a small number of atoms. In the smallest stable contacts, usually three channels contribute to the transport. We show here that the channel ensemble {T_n} of few atom contacts remains unchanged up to temperatures and magnetic fields approaching the critical temperature and the critical field, respectively, giving experimental evidence for the prediction that the conduction channels are the same in the normal and in the superconducting state.Comment: 8 pages, 5 .eps figures. To be published in Physica B 22

Acclimation to short-term low temperatures in two Eucalyptus globulus clones with contrasting drought resistance

We tested the hypothesis that Eucalyptus globulus Labill. genotypes that are more resistant to dry environments might also exhibit higher cold tolerances than drought-sensitive plants. The effect of low temperatures was evaluated in acclimated and unacclimated ramets of a drought-resistant clone (CN5) and a drought-sensitive clone (ST51) of E. globulus. We studied the plants’ response via leaf gas exchanges, leaf water and osmotic potentials, concentrations of soluble sugars, several antioxidant enzymes and leaf electrolyte leakage. Progressively lowering air temperatures (from 24/16 to 10/ 2 C, day/night) led to acclimation of both clones. Acclimated ramets exhibited higher photosynthetic rates, stomatal conductances and lower membrane relative injuries when compared to unacclimated ramets. Moreover, low temperatures led to significant increases of soluble sugars and antioxidant enzymes activity (glutathione reductase, ascorbate peroxidase and superoxide dismutases) of both clones in comparison to plants grown at control temperature (24/16 C). On the other hand, none of the clones, either acclimated or not, exhibited signs of photoinhibition under low temperatures and moderate light. The main differences in the responses to low temperatures between the two clones resulted mainly from differences in carbon metabolism, including a higher accumulation of soluble sugars in the drought-resistant clone CN5 as well as a higher capacity for osmotic regulation, as compared to the droughtsensitive clone ST51. Although membrane injury data suggested that both clones had the same inherent freezing tolerance before and after cold acclimation, the results also support the hypothesis that the droughtresistant clone had a greater cold tolerance at intermediate levels of acclimation than the drought-sensitive clone. A higher capacity to acclimate in a short period can allow a clone to maintain an undamaged leaf surface area along sudden frost events, increasing growt

Convergence of the critical attractor of dissipative maps: Log-periodic oscillations, fractality and nonextensivity

For a family of logistic-like maps, we investigate the rate of convergence to the critical attractor when an ensemble of initial conditions is uniformly spread over the entire phase space. We found that the phase space volume occupied by the ensemble W(t) depicts a power-law decay with log-periodic oscillations reflecting the multifractal character of the critical attractor. We explore the parametric dependence of the power-law exponent and the amplitude of the log-periodic oscillations with the attractor's fractal dimension governed by the inflexion of the map near its extremal point. Further, we investigate the temporal evolution of W(t) for the circle map whose critical attractor is dense. In this case, we found W(t) to exhibit a rich pattern with a slow logarithmic decay of the lower bounds. These results are discussed in the context of nonextensive Tsallis entropies.Comment: 8 pages and 8 fig

Factors Associated With Fragility Fractures In Women Over 50 Years Of Age: A Population-based Household Survey [fatores Associados A Fraturas Por Fragilidade óssea Em Mulheres Acima De 50 Anos De Idade: Um Estudo De Base Populacional]

Purpose: To analyze the prevalence of and factors associated with fragility fractures in Brazilian women aged 50 years and older. Methods: This cross-sectional population survey, conducted between May 10 and October 31, 2011, included 622 women aged ≥50 years living in a city in southeastern Brazil. A questionnaire was administered to each woman by a trained interviewer. The associations between the occurrence of a fragility fracture after age 50 years and sociodemographic data, health-related habits and problems, self-perception of health and evaluation of functional capacity were determined by the χ2 test and Poisson regression using the backward selection criteria. Results: The mean age of the 622 women was 64.1 years. The prevalence of fragility fractures was 10.8%, with 1.8% reporting hip fracture. 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