Telomerase and the search for the end of cancer.

Many of the fundamental molecular mechanisms underlying tumor biology remain elusive and, thus, developing specific anticancer therapies remains a challenge. The recently discovered relationships identified among telomeres, telomerase, aging, and cancer have opened a new avenue in tumor biology research that may revolutionize anticancer therapy. This review summarizes the critical aspects of telomerase biology that underpin the development of novel telomerase-targeting therapies for malignant diseases, and special regard is given to the aspects of telomerase that make it such an appealing target, such as the widespread expression of telomerase in cancers. Despite significant progress, issues remain to be addressed before telomerase-based therapies are truly effective and we include critical discussion of the results obtained thus far.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.molmed.2012.11.00

Genetic variation and gastric cancer risk: a field synopsis and meta-analysis.

BACKGROUND: Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has been available. METHODS: We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing stomach cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Meta-analysis was also conducted for subgroups, which were defined by ethnicity (Asian vs Caucasian), tumour histology (intestinal vs diffuse), tumour site (cardia vs non-cardia) and Helicobacter pylori infection status (positive vs negative). RESULTS: Literature search identified 824 eligible studies comprising 2 530 706 subjects (cases: 261 386 (10.3%)) and investigating 2841 polymorphisms involving 952 distinct genes. Overall, we performed 456 primary and subgroup meta-analyses on 156 variants involving 101 genes. We identified 11 variants significantly associated with disease risk and assessed to have a high level of summary evidence: MUC1 rs2070803 at 1q22 (diffuse carcinoma subgroup), MTX1 rs2075570 at 1q22 (diffuse), PSCA rs2294008 at 8q24.2 (non-cardia), PRKAA1 rs13361707 5p13 (non-cardia), PLCE1 rs2274223 10q23 (cardia), TGFBR2 rs3087465 3p22 (Asian), PKLR rs3762272 1q22 (diffuse), PSCA rs2976392 (intestinal), GSTP1 rs1695 11q13 (Asian), CASP8 rs3834129 2q33 (mixed) and TNF rs1799724 6p21.3 (mixed), with the first nine variants characterised by a low FPRP. We also identified polymorphisms with lower quality significant associations (n=110). CONCLUSIONS: We have identified several high-quality biomarkers of gastric cancer susceptibility. These data will form the backbone of an annually updated online resource that will be integral to the study of gastric carcinoma genetics and may inform future screening programmes.This is the author accepted manuscript. The final version is available from BMJ via http://dx.doi.org/10.1136/gutjnl-2015-30916

Ion mobility mass spectrometry with surface activated chemical ionisation as a method for studying the domain of water clusters

Water holds great relevance in various biological and biochemical systems. Water behaves as an excellent solvent, a reactant, a product and a catalyst of the reaction. The organisation of the water molecules, synergised by hydrogen bonds, builds up the structure of the water clusters. These water clusters significantly influence biological functions. To study the domain of water clusters using Ion mobility mass spectrometry with surface activated chemical ionisation. The experimental analysis was aimed to determine the water behaviour in terms of cluster formation before and after the application of a physical effect, namely low-frequency irradiation. A sanist platform-based spectrometer, manufactured by ISB srl with SACI version for protein analysis, was used as the equipment. Furthermore, for samples, we used pure de-ionised water, a part of which was used virgin, and another part was irradiated. Ion-mobility mass spectrometry (IM-MS) procedure was adopted as the experimental method. An electromagnetic frequency fields generator was used to subject the test samples to electromagnetic radiations between 7 Hz to 80 Hz. The presence of neutral water species was confirmed in the water samples. For the same m/z, water ion clusters in the untreated water were found to have a much higher intensity than the electromagnetically treated water. The presence of a water cluster near the (M+H)+ in electromagnetically treated dilute arginine solution was also confirmed. It is possible to detect water ion clusters by using Ion mobility mass spectrometry and SACI with low surface potential (47 V). The water cluster formation and its characteristics were found to be different in the treated and non-treated water. The electromagnetic radiations of low frequency seem to affect the hydrogen bonds of the water molecules

Felid Cardiopulmonary Nematodes: Dilemmas Solved and New Questions Posed

In the past decade cardiopulmonary nematodes affecting felids have become a core research topic in small animal parasitology. In the late 2000s, an increase in studies was followed by unexpected findings in the early 2010s, which have stimulated research teams to start investigating these intriguing parasites. Prolific scientific debate and exchanges have then fostered field and laboratory studies and epi-zootiological surveys. New data have improved basic and applied knowledge, solved dilemmas and posed new questions. This article discusses the past and present background to felid cardiopulmonary nematodes after the last few years of intense scientific research. New data which have demonstrated the key role of Aelurostrongylus abstrusus and Troglostrongylus brevior in causing respiratory infections in domestic cats, and on the nil to negligible current importance of other species, i.e., Troglostrongylus subcrenatus, Oslerus rostratus and Angiostrongylus chabaudi, are presented. Biological information and hypothesized alternative routes of infection are analysed and discussed. Novel identification and taxonomical data and issues are reported and commented upon. On the whole, recent biological, ecological and epi-zootiological information on felid meta-strongyloids is critically analysed, with the aim to answer outstanding questions, stimulate future studies, and underline new research perspectives

Estado do conhecimento sobre representações sociais e o ensino da matemática no marco da cidade educadora (2013-2020)

Por meio deste artigo objetivamos apresentar os principais resultados de pesquisas brasileiras concernentes às representações sociais, o ensino da Matemática e a cidade educadora, no recorte temporal de 2013-2020. Para tanto, fizemos um levantamento junto ao repositório de dissertações e teses no Catálogo de Teses e Dissertações da CAPES e a Biblioteca Digital Brasileira de Teses e Dissertações (BDTD) do Instituto Brasileiro de Ciência e Tecnologia, visando responder à pergunta norteadora: “No Brasil, quais produções científicas tratam das representações sociais sobre o ensino da matemática e sua interlocução com a cidade enquanto espaço educador e/ou território educativo no marco da cidade educadora?”. Os descritores que nortearam essa busca foram as seguintes expressões: “Representações Sociais” AND “Ensino da Matemática”, AND “Cidade Educadora”. Esta revisão de literatura revelou que no Brasil não há produções científicas que tratam de Representações Sociais sobre o ensino da Matemática e sua interlocução com a cidade educadora. No entanto, há um pequeno volume de pesquisas que interrelacionam Representações Sociais com o ensino da Matemática. É importante que a Matemática faça sentido e esteja articulada à vida dos estudantes, auxiliando na resolução de problemas e contribuindo para que sejam protagonistas na ação pedagógica, bem como, na compreensão do mundo a partir de suas representações

AS INFLUÊNCIAS DO PLANEJAMENTO DAS AÇÕES NA GESTÃO INSTITUCIONAL DA UFPEL

O crescente desenvolvimento das telecomunicações e da informática tem produzido relevantes mudanças nas estruturas sociais, econômicas e organizacionais, porém essa evolução também tem mostrado entraves para a gestão das organizações. Um dos problemas mais críticos é a falta de informações úteis para o processo decisório. Logo, o gerenciamento da informação passa a ser uma questão estratégica no processo de gestão nestes novos tempos de rapidez na tomada de decisão. As informações mostram-se inadequadas pela sua falta, ou por seu excesso desnecessário. Também podem estar defasadas e com acesso limitado, o que, invariavelmente, leva o gestor a tomar decisões baseadas na intuição, sem o adequado suporte da informação. Adaptar-se às contingências e às pressões do ambiente externo tornou-se um desafio constante nas organizações, onde a informação aparece como uma peça fundamental para subsidiar planos nesse complexo cenário organizacional da atualidade. As instituições federais de ensino superior não estão isentas das influências do ambiente externo. Na verdade, as universidades vivem um paradoxo. Ao mesmo tempo em que delas emergem novas tecnologias de informação e a capacitação de pessoas nas diversas extensões dessa área percebe-se a precariedade das informações e do planejamento das ações na gestão administrativa, em parte justificada pela estrutura burocrática pesada, pela resistência a mudanças, pela dependência econômica do Estado, pelo corporativismo, além de precariedade na avaliação dos resultados institucionais, dentre outros aspectos. Muitos são os impactos das mudanças sociais, políticas e econômicas nas organizações universitárias. As dificuldades, em administrar burocracias como as universidades públicas, sem uma cultura de captação de recursos extragoverno federal, demonstram a inércia da própria instituição frente a um ambiente cada vez mais incerto, e a intervenção normativa do Estado também contribuiu para restringir o desenvolvimento de planos de ações para o funcionamento e desenvolvimento das universidades. Entretanto, acredita-se que a tecnologia da informação, por sua vez, aparece como um meio facilitador para a elaboração de estratégias que atendam os objetivos institucionais, e como tal deve ser usada como um recurso interno da organização a ser tratado com o mesmo grau de importância dos demais recursos que constituem as variáveis a serem analisadas na formulação da estratégia organizacional. O planejamento e a informação têm uma relação de sinergia e integração total. A informação, para buscar resultados qualitativos, tem que ser coerente em todos os níveis de planejamento, visto que está presente em toda a organização, bem como, no ambiente externo. Maximiano (2000) destaca que em “qualquer nível de administração o planejamento compreende o processo que define as ações necessárias para enfrentar situações futuras e atingir metas” (p.395), sendo a informação a base de qualquer nível de planejamento visando uma relação mais eficaz entre organização e ambiente. Contudo, apesar das profundas mudanças tecnológicas e organizacionais, grande parte do setor público ainda permanece incapaz de dar respostas rápidas e de implantar políticas públicas que possam corresponder a um modelo renovado de relação Estado-Sociedade, no qual busca-se a melhor equalização da cidadania. Para que o Estado possa cumprir seu papel é necessária a utilização de sistemas de informação que propiciem apoio ao processo decisório, permitam a formulação de políticas adequadas e possibilitem a avaliação sistemática dos resultados. As formas de se administrar as organizações, assim como as adaptações destas ao ambiente externo e interno é uma discussão perene na esfera pública. Debater acerca da performance da universidade perpassa por propostas de mudança, de inovação, de adaptação às novas demandas por parte da comunidade universitária e da sociedade em geral, num efervescente espaço de questionamentos e descobertas que é a universidade. No intuito de mudar o cenário atual, ou seja, de propor alternativas para a elaboração e execução de um planejamento tático e operacional coerente com a realidade da universidade procurou-se, a partir deste estudo, compreender as influências do planejamento das ações da UFPel na percepção de diretores de unidades acadêmicas e administrativas, e da contribuição de técnicos da área de planejamento e de um representante da administração superior da UFPel. Para tanto, os dados foram coletados a partir da análise documental e, num segundo momento buscaram-se informações por meio de visitas às unidades acadêmicas e administrativas que, na época, estavam elaborando o Plano de Ação 2002. A análise foi feita de forma descritivo-interpretativa

Prunus Knotted-like genes. Genome-wide analysis, transcriptional response to Cytokinin in micropropagation, and rootstock transformation

Knotted1-like homeobox (KNOX) transcription factors are involved in plant development, playing complex roles in aerial organs. As Prunus species include important fruit tree crops of Italy, an exhaustive investigation of KNOX genes was performed using genomic and RNA-seq meta-analyses. Micropropagation is an essential technology for rootstock multiplication; hence, we investigated KNOX transcriptional behavior upon increasing 6-benzylaminopurine (BA) doses and the effects on GF677 propagules. Moreover, gene function in Prunus spp. was assessed by Gisela 6 rootstock transformation using fluorescence and peach KNOX transgenes. Based on ten Prunus spp., KNOX proteins fit into I-II-M classes named after Arabidopsis. Gene number, class member distribution, and chromosome positions were maintained, and exceptions supported the diversification of Prunus from Cerasus subgenera, and that of Armeniaca from the other sections within Prunus. Cytokinin (CK) cis-elements occurred in peach and almond KNOX promoters, suggesting a BA regulatory role in GF677 shoot multiplication as confirmed by KNOX expression variation dependent on dose, time, and interaction. The tripled BA concentration exacerbated stress, altered CK perception genes, and modified KNOX transcriptions, which are proposed to concur in in vitro anomalies. Finally, Gisela 6 transformation efficiency varied (2.6-0.6%) with the genetic construct, with 35S:GFP being more stable than 35S:KNOPE1 lines, which showed leaf modification typical of KNOX overexpression

HEp-2 Cell Classification with heterogeneous classes-processes based on K-Nearest Neighbours

We present a scheme for the feature extraction and classification of the fluorescence staining patterns of HEp-2 cells in IIF images. We propose a set of complementary processes specific to each class of patterns to search. Our set of processes consists of preprocessing,features extraction and classification. The choice of methods, features and parameters was performed automatically, using the Mean Class Accuracy (MCA) as a figure of merit. We extract a large number (108) of features able to fully characterize the staining pattern of HEp-2 cells. We propose a classification approach based on two steps: the first step follows the one-against-all(OAA) scheme, while the second step follows the one-against-one (OAO) scheme. To do this, we needed to implement 21 KNN classifiers: 6 OAA and 15 OAO. Leave-one-out image cross validation method was used for the evaluation of the results

An Evaluation of Energy and Economic Efficiency in Residential Buildings Sector: A Multi-criteria Analisys on an Italian Case Study

The aim of the paper is to evaluate by means of a multi-criteria analysis (Multi Criteria Decision Making - MCDM) the multiplicity of measures regarding energy efficiency and reduction in consumption of fossil fuels, with relative implementation of integrated renewable energy sources, for planning and renovation of single family residential buildings. The work analize the energy (thermal, electrical) consumed by a building of this type (an Italian case study), and, for the choice of the best technology to adopt for environmental heating (hot sanitary water and cooling), a MCDM model was used, which, in addition to economic evaluation, incorporates too energy efficiency, the reduction of CO2 emissions, the ease of procurement of raw material and the governative incentives available. Our results underline that the best solution concerns the installation of solar thermal panels combined with the heat pump. Keywords: energy efficiency, economic evaluation, residential buildings JEL Classifications: Q410, Q420, L94

Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival

<p>Abstract</p> <p>Background</p> <p>The detection of circulating tumor cells (CTC) is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma.</p> <p>Methods</p> <p>Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR) for the expression of four CTC related genes: carcinoembryonic antigen (CEA), cytokeratin-19 (CK19), vascular endothelial growth factor (VEGF) and Survivin (BIRC5).</p> <p>Results</p> <p>Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome.</p> <p>Conclusions</p> <p>Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients.</p