Origins and genetic legacy of prehistoric dogs

Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry

Paradigmatic or Critical? Resilience as a New Turn in EU Governance for the Neighbourhood

Rising from the margins of EU aid documents, resilience became a centrepiece of the 2016 EU Global Security Strategy, especially in relation to the neighbourhood. While new resilience-thinking may signify another paradigmatic shift in EU modus operandi, the question that emerges is whether it is critical enough to render EU governance a new turn, to make it sustainable? This article argues that in order for resilience-framed governance to become more effective, the EU needs not just engage with ‘the local’ by way of externally enabling their communal capacity. More crucially, the EU needs to understand resilience for what it is – a self-governing project – to allow ‘the local’ an opportunity to grow their own critical infrastructures and collective agency, in their pursuit of ‘good life’. Is the EU ready for this new thinking, and not just rhetorically or even methodologically when creating new instruments and subjectivities? The bigger question is whether the EU is prepared to critically turn the corner of its neoliberal agenda to accommodate emergent collective rationalities of self-governance as a key to make its peace-building project more successful

Early phase clinical trials of anticancer agents in children and adolescents — an ITCC perspective

In the past decade, the landscape of drug development in oncology has evolved dramatically; however, this paradigm shift remains to be adopted in early phase clinical trial designs for studies of molecularly targeted agents and immunotherapeutic agents in paediatric malignancies. In drug development, prioritization of drugs on the basis of knowledge of tumour biology, molecular 'drivers' of disease and a drug's mechanism of action, and therapeutic unmet needs are key elements; these aspects are relevant to early phase paediatric trials, in which molecular profiling is strongly encouraged. Herein, we describe the strategy of the Innovative Therapies for Children with Cancer (ITCC) Consortium, which advocates for the adoption of trial designs that enable uninterrupted patient recruitment, the extrapolation from studies in adults when possible, and the inclusion of expansion cohorts. If a drug has neither serious dose-related toxicities nor a narrow therapeutic index, then studies should generally be started at the adult recommended phase II dose corrected for body surface area, and act as dose-confirmation studies. The use of adaptive trial designs will enable drugs with promising activity to progress rapidly to randomized studies and, therefore, will substantially accelerate drug development for children and adolescents with cancer

Molecular heterogeneity and CXorf67 alterations in posterior fossa group A (PFA) ependymomas

Of nine ependymoma molecular groups detected by DNA methylation profiling, the posterior fossa type A (PFA) is most prevalent. We used DNA methylation profiling to look for further molecular heterogeneity among 675 PFA ependymomas. Two major subgroups, PFA-1 and PFA-2, and nine minor subtypes were discovered. Transcriptome profiling suggested a distinct histogenesis for PFA-1 and PFA-2, but their clinical parameters were similar. In contrast, PFA subtypes differed with respect to age at diagnosis, gender ratio, outcome, and frequencies of genetic alterations. One subtype, PFA-1c, was enriched for 1q gain and had a relatively poor outcome, while patients with PFA-2c ependymomas showed an overall survival at 5 years of > 90%. Unlike other ependymomas, PFA-2c tumors express high levels of OTX2, a potential biomarker for this ependymoma subtype with a good prognosis. We also discovered recurrent mutations among PFA ependymomas. H3 K27M mutations were present in 4.2%, occurring only in PFA-1 tumors, and missense mutations in an uncharacterized gene, CXorf67, were found in 9.4% of PFA ependymomas, but not in other groups. We detected high levels of wildtype or mutant CXorf67 expression in all PFA subtypes except PFA-1f, which is enriched for H3 K27M mutations. PFA ependymomas are characterized by lack of H3 K27 trimethylation (H3 K27-me3), and we tested the hypothesis that CXorf67 binds to PRC2 and can modulate levels of H3 K27-me3. Immunoprecipitation/mass spectrometry detected EZH2, SUZ12, and EED, core components of the PRC2 complex, bound to CXorf67 in the Daoy cell line, which shows high levels of CXorf67 and no expression of H3 K27-me3. Enforced reduction of CXorf67 in Daoy cells restored H3 K27-me3 levels, while enforced expression of CXorf67 in HEK293T and neural stem cells reduced H3 K27-me3 levels. Our data suggest that heterogeneity among PFA ependymomas could have clinicopathologic utility and that CXorf67 may have a functional role in these tumors

Variation of tibial plateau geometry and cruciate ligament coordinates in six breeds of dogs

Onar, Vedat/0000-0002-8359-243X; OCAL, M. Kamil/0000-0001-7723-5586WOS: 000316922300007PubMed: 23154751Objectives: The first aim of this study was to examine whether or not variations concerning the conformational characteristics of the proximal surface of the tibial plateau exist among six different dog breeds as well as within the same breed. The second aim of this study was to determine the coordinates of the cruciate ligaments. Methods: One hundred and four tibias of 52 mature dogs from six different breeds were used. Photographs of the proximal surface of tibial plateau were taken, and measurements for the length, width and area of the tibial plateau, and the lateral and medial condyles were taken. In addition, the intercondylar width, height of Gerdy's tubercle, popliteal notch depth, and extensor groove depth were measured and recorded. The quotients from these measurements were calculated and compared amongst the dog breeds. The coordinates of the cruciate ligaments, according to the centre of tibial plateau, were also determined. Results: Based on the calculated quotients, variations in the geometry of the tibial plateau geometry were common among the breeds. Within the same breed, on the other hand, length and width measurements of the tibial plateau were the least variable parameters among the other parameters examined. The cranial cruciate ligament was located in front of the surface centre of tibial plateau in all breeds. The position of cranial cruciate ligament was more variable in the craniocaudal direction than that observed in the mediolateral direction; this was the exact opposite of caudal cruciate ligament. Clinical significance: The inter-breed variations of the quotients determined in the present study may facilitate attempts aimed to assess the risk factors of stifle joint injury and to design total knee prostheses

Культура «верхнего» и «нижнего» интернета в молодежной среде

Actual web culture includes so called “higher” and “bottom” styles in social nets communication. “VKontakte” represents wide range of youth styles depending on themes, auditorium and volume of visitors and subscriptions.В статье рассмотрены различия интернет-культур так называемого «верхнего» и «нижнего» интернета и групп в социальной сети «ВКонтакте». Выявлена специфика интернет-культур от темы, аудитории и количества посещений (подписчиков того или иного ресурса)

The effect of atorvastatin on hemorheological parameters in rabbits fed on a normal diet

The effects of statins have been investigated mostly in hyperlipidemic states so far. We analysed blood cholesterol, triglyceride, albumin, fibrinogen and gammaglobulin levels, haematocrite, hemoglobin, erythrocyte, leukocyte and platelet counts, blood and plasma viscosity and erythrocyte rigidity in 12 rabbits fed on a normal diet (chow) which were given 1 mg/kg/day atorvastatin for 4 weeks. Compared to the baseline levels, erythrocyte rigidity (k=0.12+/-0.05 vs. k=0.7+/-0.02) and gammaglobulin levels (1.03+/-0.23 g/dl vs. 0.78+/-0.27 g/dl) decreased significantly (p=0.008 and p=0.025, respectively). Blood lipids, hematological variables, blood and plasma viscosity did not change statistically. Our findings imply that in a normolipemic state, statins given in low doses may improve erythrocyte rigidity without altering blood lipids in short term. Decreased plasma gammaglobulin levels may be reflecting their immunomodulatory effects