Transgenic Mice for Intersectional Targeting of Neural Sensors and Effectors with High Specificity and Performance

SummaryAn increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity.Video Abstrac

Induced Pluripotent Stem Cell Lines Derived from Equine Fibroblasts

The domesticated horse represents substantial value for the related sports and recreational fields, and holds enormous potential as a model for a range of medical conditions commonly found in humans. Most notable of these are injuries to muscles, tendons, ligaments and joints. Induced pluripotent stem (iPS) cells have sparked tremendous hopes for future regenerative therapies of conditions that today are not possible to cure. Equine iPS (EiPS) cells, in addition to bringing promises to the veterinary field, open up the opportunity to utilize horses for the validation of stem cell based therapies before moving into the human clinical setting. In this study, we report the generation of iPS cells from equine fibroblasts using a piggyBac (PB) transposon-based method to deliver transgenes containing the reprogramming factors Oct4, Sox2, Klf4 and c-Myc, expressed in a temporally regulated fashion. The established iPS cell lines express hallmark pluripotency markers, display a stable karyotype even during long-term culture, and readily form complex teratomas containing all three embryonic germ layer derived tissues upon in vivo grafting into immunocompromised mice. Our EiPS cell lines hold the promise to enable the development of a whole new range of stem cell-based regenerative therapies in veterinary medicine, as well as aid the development of preclinical models for human applications. EiPS cell could also potentially be used to revive recently extinct or currently threatened equine species

Analysing the attributes of Comprehensive Cancer Centres and Cancer Centres across Europe to identify key hallmarks.

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

Fatores que influenciaram no desempenho de alianças estratégicas firmadas entre empresas do real estatebrasileiro

ResumoO período entre 2006 e 2009 foi caracterizado pela realização de um grande volume de alianças estratégicas entre empresas do real estate brasileiro, cuja estratégia foi adotada por diversas companhias, que, após abertura de capital, traçaram metas agressivas de crescimento. Passados aproximadamente três anos do início dessas parcerias, a partir de meados de 2010, ao dar início à apuração de resultados dos empreendimentos objeto de tais parcerias, as empresas registraram resultados muito abaixo do planejado, em alguns casos resultados negativos. Este artigo tem como objetivo apresentar uma análise diagnóstica dos principais fatores de dificuldade que influenciaram no desempenho de tais parcerias, assim como as principais vantagens identificadas. A pesquisa foi realizada por meio de estudo de caso múltiplo, cujos resultados poderão contribuir para o planejamento de futuras parcerias entre empresas do setor

Fatores que influenciaram no desempenho de alianças estratégicas firmadas entre empresas do real estatebrasileiro

ResumoO período entre 2006 e 2009 foi caracterizado pela realização de um grande volume de alianças estratégicas entre empresas do real estate brasileiro, cuja estratégia foi adotada por diversas companhias, que, após abertura de capital, traçaram metas agressivas de crescimento. Passados aproximadamente três anos do início dessas parcerias, a partir de meados de 2010, ao dar início à apuração de resultados dos empreendimentos objeto de tais parcerias, as empresas registraram resultados muito abaixo do planejado, em alguns casos resultados negativos. Este artigo tem como objetivo apresentar uma análise diagnóstica dos principais fatores de dificuldade que influenciaram no desempenho de tais parcerias, assim como as principais vantagens identificadas. A pesquisa foi realizada por meio de estudo de caso múltiplo, cujos resultados poderão contribuir para o planejamento de futuras parcerias entre empresas do setor

Gene Expression in Xenopus Embryos after Methylmercury Exposure. A Search for Molecular Biomarkers.

Abstract not availableJRC.I-Institute for Health and Consumer Protection (Ispra

POMI: An Expert System for Integrated Pest Management of Apple Orchards

This paper describes an Expert System for apple orchard integrated control. The system consists of two parts. In the first one, help to the agricultural producer is provided in classifying the producer observations. In the second part an interactive abductive module suggests explanations of those observations. Classification has been implemented with the aid of discrimination net techniques. The abductive module exploits results from the parsimonious covering theory by Peng and Reggia. The system has been implemented in KEE with an extensive use of the graphical tools provided by the language. In a future work it will be extended with a module responsible for treatment suggestion. 1 Introduction The general reevaluation of ecological-environmental problems has increased interest in those forms of agriculture characterized by reduced environmental impact. In fact, the traditional model of agricultural development, based on massive introduction of innovative technologies, while allowi..