Survival, classifications, and desmosomal plaque genes in non-small cell lung cancer.

Novel biomarkers are required to improve prognostic predictions obtained with lung cancer staging systems. This study of 62 surgically-treated Non-Small Cell Lung Cancer (NSCLC) patients had two objectives: i) to compare the predictive value of T-stage classifications between the 6(th) and 7(th) editions of the Tumor, Node, and Metastasis staging system (TNM); and ii) to examine the association of Pkp1 and/or Krt15 gene expression with survival and outcomes. Multivariate and Kaplan-Meier survival analyses were performed, examining the relationship of survival with T-stage, recurrence, and TNM-stage (by each TNM edition) and with the single/combined expression of Pkp1 and/or Krt15 genes. Five-year survival rates only significantly differed as a function of T-stage in patients without recurrence when estimated using the 6(th) edition of the TNM classification and only in patients in pathologic TNM-stage IA using the 7(th). Overall survival for patients with elevated expression of both genes was 13.5 months in those with adenocarcinoma and 34.6 months in those with squamous cell carcinoma. Overall survival was 30.4 months in patients with Pkp1 gene upregulation and 30.9 months in those with Krt15 gene upregulation. In conclusion, survival estimations as a function of T-staging differed between the 6(th) and 7(th) editions of TNM. Overall survival differed according to the expression of Pkp1 and/or Krt15 genes, although this relationship did not reach statistical significance.

Could radiotherapy effectiveness be enhanced by electromagnetic field treatment?

One of the main goals in radiobiology research is to enhance radiotherapy effectiveness without provoking any increase in toxicity. In this context, it has been proposed that electromagnetic fields (EMFs), known to be modulators of proliferation rate, enhancers of apoptosis and inductors of genotoxicity, might control tumor recruitment and, thus, provide therapeutic benefits. Scientific evidence shows that the effects of ionizing radiation on cellular compartments and functions are strengthened by EMF. Although little is known about the potential role of EMFs in radiotherapy (RT), the radiosensitizing effect of EMFs described in the literature could support their use to improve radiation effectiveness. Thus, we hypothesized that EMF exposure might enhance the ionizing radiation effect on tumor cells, improving the effects of RT. The aim of this paper is to review reports of the effects of EMFs in biological systems and their potential therapeutic benefits in radiotherapy.

Towards a Union of Citizens and States: Negotiating Transnational Democracy in Europe

Aquest article dóna un cop d'ull més de prop com les qüestions de legitimitat democràtica es van negociar durant la primera de les tres etapes de la redacció de la Constitució, en la Convenció sobre el Futur d'Europa (febrer de 2002-juliol 2003), i per la posterior Conferència Intergovernamental (juliol de 2003 a juny de 2004). L'objectiu d'aquesta anàlisi és avaluar el grau en què els redactors de la Comissió Europea s'han resolt els problemes de disputes sobre la democràcia postnacional que es van debatre en la Convenció

Role of Sam68 in post-transcriptional gene regulation.

The STAR family of proteins links signaling pathways to various aspects of post-transcriptional regulation and processing of RNAs. Sam68 belongs to this class of heteronuclear ribonucleoprotein particle K (hnRNP K) homology (KH) single domain-containing family of RNA-binding proteins that also contains some domains predicted to bind critical components in signal transduction pathways. In response to phosphorylation and other post-transcriptional modifications, Sam68 has been shown to have the ability to link signal transduction pathways to downstream effects regulating RNA metabolism, including transcription, alternative splicing or RNA transport. In addition to its function as a docking protein in some signaling pathways, this prototypic STAR protein has been identified to have a nuclear localization and to take part in the formation of both nuclear and cytosolic multi-molecular complexes such as Sam68 nuclear bodies and stress granules. Coupling with other proteins and RNA targets, Sam68 may play a role in the regulation of differential expression and mRNA processing and translation according to internal and external signals, thus mediating important physiological functions, such as cell death, proliferation or cell differentiation.

Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach.

Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice.

Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children.

BACKGROUND AND AIM: Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations of the MEFV gene. We analyse the impact of ethnic, environmental and genetic factors on the severity of disease presentation in a large international registry. METHODS: Demographic, genetic and clinical data from validated paediatric FMF patients enrolled in the Eurofever registry were analysed. Three subgroups were considered: (i) patients living in the eastern Mediterranean countries; (ii) patients with an eastern Mediterranean ancestry living in western Europe; (iii) Caucasian patients living in western European countries. A score for disease severity at presentation was elaborated. RESULTS: Since November 2009, 346 FMF paediatric patients were enrolled in the Eurofever registry. The genetic and demographic features (ethnicity, age of onset, age at diagnosis) were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. European patients had a lower frequency of the high penetrance M694V mutation and a significant delay of diagnosis (p<0.002). Patients living in eastern Mediterranean countries had a higher frequency of fever episodes/year and more frequent arthritis, pericarditis, chest pain, abdominal pain and vomiting compared to the other two groups. Multivariate analysis showed that the variables independently associated with severity of disease presentation were country of residence, presence of M694V mutation and positive family history. CONCLUSIONS: Eastern Mediterranean FMF patients have a milder disease phenotype once they migrate to Europe, reflecting the effect of environment on the expression of a monogenic disease.

International analysis of the countries where Brazilian franchise chains operate

This paper aims to demonstrate which external environment factors are involved in the international commitment of Brazilian franchise chains. Our objectives herein are to understand which external country characteristics lead to international franchising operations and to ascertain the influence of such characteristics in the commitment of franchise chains in each country they operate in. The database has 54 Brazilian franchise chains with international operations in 26 countries, which implies in 157 franchises operating abroad. Regarding external environment factors, the independent variables form a group divided into market opportunity and business efficiency – trust and ease to doing business. The result of the three distinct clusters show how the market opportunity and the business efficiency (trust and ease in doing business) work as drivers to the international operation of Brazilian franchises. The paper shows that the franchise chains operating in the USA (cluster 3) have an inferior international commitment in comparison with the franchises which operate in developed countries and in small Latin American countries (cluster 2). It is also possible to notice a large number of franchises that operate in underdeveloped countries from Latin America and Africa (cluster 1) with worse business efficiency due to the advantage of learning how to operate in a country that could have some similarities with Brazil

Open minded and open access: introducing NeoBiota, a new peer-reviewed journal of biological invasions

The Editorial presents the focus, scope, policies, and the inaugural issue of NeoBiota, a new open access peer-reviewed journal of biological invasions. The new journal NeoBiota is a continuation of the former NEOBIOTA publication series. The journal will deal with all aspects of invasion biology and impose no restrictions on manuscript size neither on use of color. NeoBiota implies an XML-based editorial workflow and several cutting-edge innovations in publishing and dissemination, such as semantic markup of and enhancements to published texts, data publication, and extensive cross-linking within the journal and to external sources

New Radicals and new applications of Dynamic Nuclear Polarization of biological systems

Dynamic Nuclear Polarization (DNP) is an emerging technique that could revolutionize the NMR study of small molecules at very low concentrations by the increase in sensitivity that results from transfer of polarization between electronic and nuclear spins. Although the underlying physics has been known for a long time, in the last few years there has been a lot of excitement on the chemistry and biology NMR community caused by the demonstration that the highly polarized nuclei that are prepared in solid state at very low temperatures (1-2 K) could be rapidly transferred to liquid samples at room temperature and studied in solution by conventional NMR techniques. In favorable cases several order of magnitude increases in sensitivity have been achieved. The technique is now mature enough that a commercial instrument is available. The efficiency of DNP depends on two crucial aspects: i) the efficiency of the nuclear polarization process and ii) the efficiency of the transfer from the initial solid state to the fluid state in which NMR is measured. The preferred areas of application (iii) will be dictated by situations in which the low concentration of the sample or its intrinsic low receptivity are the limiting factors .

Allergo-immunologie. 2. Faut-il se méfier des agents biologiques [Allergy-immunology. Do we have to be afraid of biological agents?].

Biologicals are now fully part of our daily therapeutic strategies. However, even if their high specificity seems to induce less risk compared to older or classical immunosuppressive drugs, there are not harmless especially regarding infectious but also immunological and allergic issues. Recent attempts to better characterize the different types of reactions to biologicals should be reported, allowing us better understanding of the risk to maintain these therapies or defining how to improve the methods to use them.

Organization of pre-Variscan basement areas at the north-Gondwanan margin

Pre-Variscan basement elements of Central Europe appear in polymetamorphic domains juxtaposed through Variscan and/or Alpine tectonic events. Consequently, nomenclatures and zonations applied to Variscan and Alpine structures, respectively, cannot be valid for pre-Variscan structures. Comparing pre-Variscan relics hidden in the Variscan basement areas of Central Europe, the Alps included, large parallels between the evolution of basement areas of future Avalonia and its former peri-Gondwanan eastern prolongations (e.g. Cadomia, Intra-Alpine Terrane) become evident. Their plate-tectonic evolution from the Late Proterozoic to the Late Ordovician is interpreted as a continuous Gondwana-directed evolution. Cadomian basement, late Cadomian granitoids, late Proterozoic detrital sediments and active margin settings characterize the pre-Cambrian evolution of most of the Gondwana-derived microcontinental pieces. Also the Rheic ocean, separating Avalonia from Gondwana, should have had, at its early stages, a lateral continuation in the former eastern prolongation of peri-Gondwanan microcontinents (e.g. Cadomia, Intra-Alpine Terrane). Subduction of oceanic ridge (Proto-Tethys) triggered the break-off of Avalonia, whereas in the eastern prolongation, the presence of the ridge may have triggered the amalgamation of volcanic arcs and continental ribbons with Gondwana (Ordovician orogenic event). Renewed Gondwana-directed subduction led to the opening of Palaeo-Tethys.