Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium.

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).

Effects of erosion and deposition on particle size distribution of deposited farmland soils on the chinese loess plateau

Particle size distribution (PSD) in the soil profile is strongly related to erosion, deposition, and physical and chemical processes. Water cycling and plant growth are also affected by PSD. Material sedimented upstream of the dam constructions formed large areas of deposited farmland (DF) soils on the Chinese Loess Plateau (CLP), which has been the site of the most severe soil erosion in the world. Two DFs without tillage on the CLP were chosen to study the combined effect of erosion and check dams on PSD. Eighty-eight layers (each 10 cm thick) of filled deposited farmland (FDF) soils and 22 layers of silting deposited farmland (SDF) soils of each studied soil profile were collected and 932 soil samples were investigated using laser granulometry. The particle sizes were stratified in both DFs based on soil properties and erosion resistance. The obtained results of clay and silt fractions showed similar horizontal distribution, indicating parallel characteristics of erosion and deposition processes. Fine sand represented the largest fraction, suggesting the preferential detachment of this fraction. The most erodible range of particle sizes was 0.25-0.5 mm, followed by 0.2-0.25 mm in the studied soil profiles. The correlation between particle size and soil water contents tended to increase with increasing water contents in FDF. Due to the abundant shallow groundwater, the relationship between particle size and soil water content in SDF was lost. Further studies on PSD in the DF area are needed to enhance the conservation management of soil and water resources in this region.

Metodologia para projeto de planejamento estratégico de informações alinhado ao planejamento estratégico: a experiência do Senac-PR

O objetivo desse artigo é descrever uma metodologia para projeto de Planejamento Estratégico de Informações (PEI) alinhado ao Planejamento Estratégico Organizacional, a partir de um estudo de caso no Serviço Nacional de Aprendizagem Comercial do Paraná, e os seus respectivos desafios e dificuldades. Os resultados e as contribuições relatam sobre a viabilidade prática do projeto PEI e os detalhes da execução de sua metodologia. A conclusão reitera a importância da metodologia do PEI, implementada e aceita como uma ferramenta para contribuir de forma efetiva nas inteligências interna, competitiva e organizacional do Senac-PR.

An integrated encyclopedia of DNA elements in the human genome.

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

Calcium phosphate transfection generates mammalian recombinant cell lines with higher specific productivity than polyfection.

Transfection with polyethylenimine (PEI) was evaluated as a method for the generation of recombinant Chinese hamster ovary (CHO DG44) cell lines by direct comparison with calcium phosphate-DNA coprecipitation (CaPO4) using both green fluorescent protein (GFP) and a monoclonal antibody as reporter proteins. Following transfection with a GFP expression vector, the proportion of GFP-positive cells as determined by flow cytometry was fourfold higher for the PEI transfection as compared to the CaPO4 transfection. However, the mean level of transient GFP expression for the cells with the highest level of fluorescence was twofold greater for the CaPO4 transfection. Fluorescence in situ hybridization on metaphase chromosomes from pools of cells grown under selective pressure demonstrated that plasmid integration always occurred at a single site regardless of the transfection method. Importantly, the copy number of integrated plasmids was measurably higher in cells transfected with CaPO4. The efficiency of recombinant cell line recovery under selective pressure was fivefold higher following PEI transfection, but the average specific productivity of a recombinant antibody was about twofold higher for the CaPO4-derived cell lines. Nevertheless, no difference between the two transfection methods was observed in terms of the stability of protein production. These results demonstrated the feasibility of generating recombinant CHO-derived cell lines by PEI transfection. However, this method appeared inferior to CaPO4 transfection with regard to the specific productivity of the recovered cell lines.

The GENCODE pseudogene resource.

BACKGROUND: Pseudogenes have long been considered as nonfunctional genomic sequences. However, recent evidence suggests that many of them might have some form of biological activity, and the possibility of functionality has increased interest in their accurate annotation and integration with functional genomics data. RESULTS: As part of the GENCODE annotation of the human genome, we present the first genome-wide pseudogene assignment for protein-coding genes, based on both large-scale manual annotation and in silico pipelines. A key aspect of this coupled approach is that it allows us to identify pseudogenes in an unbiased fashion as well as untangle complex events through manual evaluation. We integrate the pseudogene annotations with the extensive ENCODE functional genomics information. In particular, we determine the expression level, transcription-factor and RNA polymerase II binding, and chromatin marks associated with each pseudogene. Based on their distribution, we develop simple statistical models for each type of activity, which we validate with large-scale RT-PCR-Seq experiments. Finally, we compare our pseudogenes with conservation and variation data from primate alignments and the 1000 Genomes project, producing lists of pseudogenes potentially under selection. CONCLUSIONS: At one extreme, some pseudogenes possess conventional characteristics of functionality; these may represent genes that have recently died. On the other hand, we find interesting patterns of partial activity, which may suggest that dead genes are being resurrected as functioning non-coding RNAs. The activity data of each pseudogene are stored in an associated resource, psiDR, which will be useful for the initial identification of potentially functional pseudogenes.

Multicenter study of a new fully automated HBsAg screening assay with enhanced sensitivity for the detection of HBV mutants.

In a multicenter study a new, fully automated Roche Diagnostics Elecsys HBsAg II screening assay with improved sensitivity to HBsAg mutant detection was compared to well-established HBsAg tests: AxSYM HBsAg V2 (Abbott), Architect HBsAg (Abbott), Advia Centaur HBsAg (Bayer) Enzygnost HBsAg 5.0 (Dade-Behring), and Vitros Eci HBsAg (Ortho). A total of 16 seroconversion panels, samples of 60 HBsAg native mutants, and 31 HBsAg recombinant mutants, dilution series of NIBSC and PEI standards, 156 HBV positive samples comprising genotypes A to G, 686 preselected HBsAg positive samples from different stages of infection, 3,593 samples from daily routine, and 6,360 unselected blood donations were tested to evaluate the analytical and clinical sensitivity, the detection of mutants, and the specificity of the new assay. Elecsys HBsAg II showed a statistically significant better sensitivity in seroconversion panels to the compared tests. Fifty-seven out of 60 native mutants and all recombinant mutants were found positive. Among 156 HBV samples with different genotypes and 696 preselected HBsAg positive samples Elecsys HBsAg II achieved a sensitivity of 100%. The lower detection limit for NIBSC standard was calculated to be 0.025 IU/ml and for the PEI standards ad and ay it was <0.001 and <0.005 U/ml, respectively. Within 2,724 daily routine specimens and 6.360 unselected blood donations Elecsys HBsAg II showed a specificity of 99.97 and 99.88%, respectively. In conclusion the new Elecsys HBsAg II shows a high sensitivity for the detection of all stages of HBV infection and HBsAg mutants paired together with a high specificity in blood donors, daily routine samples, and potentially interfering sera.

Four decades of the independent study programmes

Sobre l'Independent Studies Programme (ISP) i el Programa d’Estudis Independents (PEI) del MACBA

Prospective study of the barriers to nutritional support in a paediatric intensive care unit : P16

Introduction and aim: Children hospitalised in a paediatric intensive care unit (PICU) are mainly fed by nutritional support (NS) which may often be interrupted. The aims of the study were to verify the relationship between prescribed (PEI) and actual energy intake (AEI) and to identify the reasons for NS interruption. Methods: Prospective study in a PICU. PEI and AEI from day 1 to 15, type of NS (enteral, parenteral, mixed), position of the feeding tube, interruptions in NS and reasons for these were noted. Inter - ruptions were classified in categories of barriers and their frequency and duration were analysed. Results: Fifteen children (24 ± 25.2 months) were studied for 84 days. The NS was exclusively enteral (69%) or mixed (31%). PEI were significantly higher than AEI (54.7 ± 32.9 vs 49.2 ± 33.6 kcal/kg, p = 0.0011). AEI represented 93% of the PEI. Ninety-eight interruptions were noted and lasted 189 h, i.e. 9.4% of the evaluated time. The most frequent barriers were nursing procedures, respiratory physiotherapy and unavailability of intravenous access. The longest were caused by the necessity to stop NS for surgery or diagnostic studies, to treat burns or to carry out medical procedures. Conclusion: AEI in PICU were inferior by 7% to PEI, considerably lower than in adult studies. Making these results available to medical staff for greater anticipation and compensation could reduce NS interruptions. Starving protocols should be reconsidered.

Improvement of productivity and polysaccharide-protein complex in Agaricus blazei

The objective of this work was to assess the productivity and polysaccharide-protein complex content of Agaricus blazei on rice straw medium, in comparison to conventional sawdust, using four casing soils. The A. blazei strain used was BCRC36814T, purchased from the Food Industry Research and Development Institute, Hsin-Chu, Taiwan. The two media were evaluated as to A. blazei productivity, harvesting time, and production costs. The experimental design used was a randomized complete block, with four replicates. Three local casing soils - Typic Paleudult (CCe), Typic Udorthent (Tq) and Oxyaquic Paleudult (TSp) - were compared to imported peat soil (PS, Saprists, Histosols), used as the control. The productivity of A. blazei using Tq and TSp soil was significantly higher. The TSp casing treatment resulted in earlier harvest by at least 14 to 27 days, when compared to the other treatments. The polysaccharide content in CCe (13.2%) and Tq soils (13.2%) did not differ significantly from the PS (13.4%) and TSp (10.6%) treatments. Local casing soils decreased the production costs of A. blazei cultivation. Composted rice straw can substitute sawdust as the culture medium for A. blazei production with increased yield.

Oligonucleotide-polyethylenimine complexes targeting retinal cells: structural analysis and application to anti-TGFbeta-2 therapy.

PURPOSE: The aim of this study was to characterize oligonucleotide-polyethylenimine (ODN/PEI) complex preparation for potential transfection of retinal cells in vitro and in vivo. METHODS: The effect of medium preparation [HEPES-buffered saline (HBS), water] on particle size and morphology was evaluated. Cultured Lewis rat retinal Müller glial (RMG) cells were transfected using fluorescein isothiocyanate (FITC)-ODN/PEI complexes specifically directed at transforming growth factor beta (TGFbeta)-2. Efficacy of transfection was evaluated using confocal microscopy, and regulation of gene expression was assayed using quantitative real-time RT-PCR and ELISA assay. One, 24, and 72 h after injection of FITC-ODN/PEI complexes into the vitreous of rat eyes, their distribution was analyzed on eye sections. RESULTS: Complexes prepared in HBS were smaller than complexes prepared in pure water and presented a core-shell structure. These particles showed a high cellular internalization efficacy, along with a significant and specific down-regulation of TGFbeta-2 expression and production in RMG cells, correlating with specific inhibition of cell growth at 72 h. In vivo, complexes efficiently transfect retinal cells and follow a transretinal migration at 24 h. After 72 h, ODN seems to preferentially target RMG cells without inducing any detectable toxicity. CONCLUSIONS: Specific down-regulation of TGFbeta-2 expression using ODN/PEI complexes may have potential interest for the treatment of retinal diseases associated with glial proliferation.

Comparative analysis of the transcriptome across distant species.

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters.

Geoambientes do Parque Estadual do Ibitipoca, município de Lima Duarte-MG

Foram identificados, mapeados e caracterizados os geoambientes do Parque Estadual do Ibitipoca (PEI), Minas Gerais, com o objetivo de subsidiar o manejo ecológico da área. Para este fim, realizaram-se coletas de solos, em pontos georreferenciados por GPS (Global Positioning System), fotointerpretações a partir de ortofotos e uso de mapas planialtimétricos, além de intenso reconhecimento de solos no campo. Oito geoambientes foram identificados e caracterizados: (1) Patamares com Espodossolos, 2) Cristas Ravinadas, 3) Escarpas, 4) Grotas, 5) Mata Baixa com Candeia, 6) Mata Alta sobre Xisto, 7) Topos Aplainados e 8) Rampas com Vegetação Aberta. Em cada ambiente a vegetação associada é fortemente condicionada pela profundidade do solo e pelo tempo de permanência de água no sistema. Os ambientes de mata, tanto sobre xistos quanto sobre quartzitos, sofrem menor estresse hídrico, seja por melhores condições físicas do solo e maior retenção de água, seja pela presença de ambiente mais ombrófilo e úmido, como nas Grotas. Os geoambientes florestados possuem concentrações de P e K mais elevadas do que nos ambientes campestres abertos. No geoambiente de Mata Baixa com Candeia, a pobreza química do substrato parece ser o impedimento à ocorrência de uma floresta mais densa. Os Campos de Altitude ocorrem nas altitudes mais elevadas no PEI, sendo desenvolvidos sobre solos mais profundos do que sob campos rupestres, onde há freqüente exposição da rocha ou solos muito rasos.

Lethal weapons : novel approaches for receptor-targeted cancer cell elimination

The currently used forms of cancer therapy are associated with drug resistance and toxicity to healthy tissues. Thus, more efficient methods are needed for cancer-specific induction of growth arrest and programmed cell death, also known as apoptosis. Therapeutic forms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are investigated in clinical trials due to the capability of TRAIL to trigger apoptosis specifically in cancer cells by activation of cell surface death receptors. Many tumors, however, have acquired resistance to TRAIL-induced apoptosis and sensitizing drugs for combinatorial treatments are, therefore, in high demand. This study demonstrates that lignans, natural polyphenols enriched in seeds and cereal, have a remarkable sensitizing effect on TRAIL-induced cell death at non-toxic lignan concentrations. In TRAIL-resistant and androgen-dependent prostate cancer cells we observe that lignans repress receptor tyrosine kinase (RTK) activity and downregulate cell survival signaling via the Akt pathway, which leads to increased TRAIL sensitivity. A structure-activity relationship analysis reveals that the γ-butyrolactone ring of the dibenzylbutyrolactone lignans is essential for the rapidly reversible TRAIL-sensitizing activity of these compounds. Furthermore, the lignan nortrachelogenin (NTG) is identified as the most efficient of the 27 tested lignans and norlignans in sensitization of androgen-deprived prostate cancer cells to TRAIL-induced apoptosis. While this combinatorial anticancer approach may leave normal cells unharmed, several efficient cancer drugs are too toxic, insoluble or unstable to be used in systemic therapy. To enable use of such drugs and to protect normal cells from cytotoxic effects, cancer-targeted drug delivery vehicles of nanometer scale have recently been generated. The newly developed nanoparticle system that we tested in vitro for cancer cell targeting combines the efficient drug-loading capacity of mesoporous silica to the versatile particle surface functionalization of hyperbranched poly(ethylene imine), PEI. The mesoporous hybrid silica nanoparticles (MSNs) were functionalized with folic acid to promote targeted internalization by folate receptor overexpressing cancer cells. The presented results demonstrate that the developed carrier system can be employed in vitro for cancer selective delivery of adsorbed or covalently conjugated molecules and furthermore, for selective induction of apoptotic cell death in folate receptor expressing cancer cells. The tested carrier system displays potential for simultaneous delivery of several anticancer agents specifically to cancer cells also in vivo.