Vimentin Is a Novel Anti-Cancer Therapeutic Target; Insights from In Vitro and In Vivo Mice Xenograft Studies

BACKGROUND:Vimentin is a ubiquitous mesenchymal intermediate filament supporting mechano-structural integrity of quiescent cells while participating in adhesion, migration, survival, and cell signaling processes via dynamic assembly/disassembly in activated cells. Soft tissue sarcomas and some epithelial cancers exhibiting "epithelial to mesenchymal transition" phenotypes express vimentin. Withaferin-A, a naturally derived bioactive compound, may molecularly target vimentin, so we sought to evaluate its effects on tumor growth in vitro and in vivo thereby elucidating the role of vimentin in drug-induced responses. METHODS AND FINDINGS:Withaferin-A elicited marked apoptosis and vimentin cleavage in vimentin-expressing tumor cells but significantly less in normal mesenchymal cells. This proapoptotic response was abrogated after vimentin knockdown or by blockade of caspase-induced vimentin degradation via caspase inhibitors or overexpression of mutated caspase-resistant vimentin. Pronounced anti-angiogenic effects of Withaferin-A were demonstrated, with only minimal effects seen in non-proliferating endothelial cells. Moreover, Withaferin-A significantly blocked soft tissue sarcoma growth, local recurrence, and metastasis in a panel of soft tissue sarcoma xenograft experiments. Apoptosis, decreased angiogenesis, and vimentin degradation were all seen in Withaferin-A treated specimens. CONCLUSIONS:In light of these findings, evaluation of Withaferin-A, its analogs, or other anti-vimentin therapeutic approaches in soft tissue sarcoma and "epithelial to mesenchymal transition" clinical contexts is warranted

Foraging ecology of Mediterranean juvenile loggerhead turtles: insights from C and N stable isotope ratios

Bycatch is one of the key threats to juvenile marine turtles in the Mediterranean Sea. As fishing methods are regional or habitat specific, the susceptibility of marine turtles may differ according to inter- and intra-population variations in foraging ecology. An understanding of these variations is necessary to assess bycatch susceptibility and to implement region-specific management. To determine if foraging ecology differs with region, sex, and size of juvenile loggerhead turtles (Caretta caretta), stable isotope analysis of carbon and nitrogen was performed on 171 juveniles from a range of foraging regions across the central and eastern Mediterranean Sea. Isotope ratios differed with geographical region, likely due to baseline variations in δ13C and δ15N values. The absence of sex-specific differences suggests that within an area, all comparably sized animals likely exploit similar foraging strategies, and therefore, their susceptibility to fisheries threats will likely be similar. The isotope ratios of juveniles occupying the North East Adriatic and North Levantine basin increased with size, potentially due to increased consumption of more prey items at higher trophic levels from a more neritic source. Isotope ratios of juveniles with access to both neritic and oceanic habitats did not differ with size which is consistent with them consuming prey items from both habitats interchangeably. With foraging habitats exploited differently among size classes in a population, the susceptibility to fisheries interactions will likely differ with size; therefore, region-specific management approaches will be needed

Mediterranean sea turtles: current knowledge and priorities for conservation and research

The available information regarding the 2 sea turtle species breeding in the Mediterranean (loggerhead turtle Caretta caretta and green turtle Chelonia mydas) is reviewed, including biometrics and morphology, identification of breeding and foraging areas, ecology and behaviour, abundance and trends, population structure and dynamics, anthropogenic threats and conservation measures. Although a large body of knowledge has been generated, research efforts have been inconsistently allocated across geographic areas, species and topics. Significant gaps still exist, ranging from the most fundamental aspects, such as the distribution of major nesting sites and the total number of clutches laid annually in the region, to more specific topics like age at maturity, survival rates and behavioural ecology, especially for certain areas (e.g. south-eastern Mediterranean). These gaps are particularly marked for the green turtle. The recent positive trends of nest counts at some nesting sites may be the result of the cessation of past exploitation and decades of conservation measures on land, both in the form of national regulations and of continued active protection of clutches. Therefore, the current status should be considered as dependent on such ongoing conservation efforts. Mitigation of incidental catch in fisheries, the main anthropogenic threat at sea, is still in its infancy. From the analysis of the present status a comprehensive list of research and conservation priorities is proposed

Evaluation Strategies for HCI Toolkit Research

Toolkit research plays an important role in the field of HCI, as it can heavily influence both the design and implementation of interactive systems. For publication, the HCI community typically expects toolkit research to include an evaluation component. The problem is that toolkit evaluation is challenging, as it is often unclear what ‘evaluating’ a toolkit means and what methods are appropriate. To address this problem, we analyzed 68 published toolkit papers. From our analysis, we provide an overview of, reflection on, and discussion of evaluation methods for toolkit contributions. We identify and discuss the value of four toolkit evaluation strategies, including the associated techniques that each employs. We offer a categorization of evaluation strategies for toolkit researchers, along with a discussion of the value, potential limitations, and trade-offs associated with each strategy

Student-centered Pedagogy and Real-world Research: Using Documents as Sources of Data in Teaching Social Science Skills and Methods

This teaching note describes the design and implementation of an activity in a 90-minute teaching session that was developed to introduce a diverse cohort of first year criminology and sociology students to the use of documents as sources of data. This approach was contextualised in real world research through scaffolded, student-centered tasks focused on archival material and a contemporary estate agents’ brochure so as to investigate changes in the suburbs that surround a university in North London, United Kingdom. In order to contribute to the growing discussion on pedagogic dialogical spaces in teaching research methods, we provide empirical evidence of students’ greater engagement via group work and the opportunity to draw on experiential knowledge in analysing sources. Beyond stimulating students’ engagement with research skills and methods, the data also shows the value of our approach in helping students to develop their analytical skills, particularly through a process of comparison and contrast