Tumor Antigen Acrosin Binding Protein Normalizes Mitotic Spindle Function to Promote Cancer Cell Proliferation

Cancer cells manage to divide in the context of gross chromosomal abnormalities. These abnormalities can promote bypass of normal restraints on cell proliferation, but at a cost of mitotic vulnerabilities that can be attacked by chemotherapy. Determining how cancer cells balance these issues may permit chemotherapeutic sensitivity to be leveraged more efficiently. From a pan-genomic siRNA screen for modifiers of chemoresponsiveness, we identified the tumor antigen ACRBP/OY-TES-1 as a specifier of paclitaxel resistance. ACRBP expression is normally restricted to the testes but detected in a wide variety of cancers, including most ovarian cancers. We found that ACRBP is both necessary and sufficient for paclitaxel resistance in ovarian cancer cell lines and ovarian tumor explants. Moreover, high ACRBP expression correlated with reduced survival time and faster relapse among ovarian cancer patients. We identified the mitotic spindle protein NuMA as an ACRBP-interacting protein that could account for the effects of ACRBP on paclitaxel sensitivity. In cancer cells, ACRBP restricted a NuMA-dependent abrogation of mitotic spindle assembly that is otherwise pathologic. As a consequence, ACRBP depletion resulted in mitotic errors and reduced proliferative fitness that could be rescued by NuMA co-depletion. We propose that the co-dependent relationship of ACRBP and NuMA in cancer cells reflects their passage through a selection bottleneck during tumor evolution, one which requires the acquisition of traits which normalize mitotic perturbations that originally drove the plasticity of a pre-neoplastic genome. The molecular definition of such traits as defined by the ACRBP-NuMA complex may represent conceptually ideal intervention targets, based on the wide therapeutic windows they may offer

'Support our networking and help us belong!': listening to beginning secondary school science teachers

This study, drawing on the voice of beginning teachers, seeks to illuminate their experiences of building professional relationships as they become part of the teaching profession. A networking perspective was taken to expose and explore the use of others during the first three years of a teacher’s workplace experience. Three case studies, set within a wider sample of 11 secondary school science teachers leaving one UK university’s PostGraduate Certificate in Education, were studied. The project set out to determine the nature of the networks used by teachers in terms of both how they were being used for their own professional development and perceptions of how they were being used by others in school. Affordances and barriers to networking were explored using notions of identity formation through social participation. The focus of the paper is on how the teachers used others to help shape their sense of belonging to this, their new workplace. The paper develops ideas from network theories to argue that membership of the communities are a subset of the professional inter‐relationships teachers utilise for their professional development. During their first year of teaching, eight teachers were interviewed, completing 13 semi‐structured interviews. This was supplemented in Year 2 by a questionnaire survey of their experiences. In the third year of the programme, 11 teachers (including the original sample of eight) were surveyed using a network mapping tool in which they represented their communications with people, groups and resources. Finally, three of the teachers (common to both samples) were then interviewed specifically about their networking practices and experiences using the generation of their network map as a stimulated recall focus. The implications of the analysis of these accounts are that these beginning teachers did not perceive of themselves wholly as novices and that their personal aspirations to increase participation in practical science, develop a career or work for pupils holistically did not always sit comfortably with the school communities into which they were being accommodated. While highlighting the importance of trust and respect in establishing relationships, these teachers’ accounts highlight the importance of finding ‘peers’ from whom they can find support and with whom they can reflect and potentially collaborate towards developing practice. They also raise questions about who these ‘peers’ might be and where they might be found

The origins of the Selden map of China: scientific analysis of the painting materials and techniques using a holistic approach

Since the 'rediscovery' of the Selden map of China, an early seventeenth century map of Asia, in the Bodleian Library in Oxford, the importance of the map in our understanding of globalisation in the early seventeenth century has been recognised. One of the unresolved questions is the origin of the map. This paper addresses the question through material evidence provided by a holistic approach using a suite of complementary analytical techniques. The map was examined in situ and non-invasively by a remote spectral imaging instrument (PRISMS) modified for close range imaging, which was followed by a range of complementary techniques applied to a number of detached fragments, though most of the techniques are non-invasive and can be applied to the map directly in the future. The binding medium was found to be a gum, almost certainly gum Arabic, rather than the animal glue commonly used in Chinese paintings. Some of the pigments and their usage were found to be at odds with the common practice in paintings from China. The detection of gum Arabic, a binding medium used by the Europeans, South and West Asians and the use of a mixture of orpiment and indigo, commonly found in European, South and West Asian paintings gives further evidence on the unusual origins of this map. The likely detection of a basic copper chloride, such as atacamite, in the green areas suggests an influence from the South and West Asian rather than the European tradition. Detailed analysis of the various spectral bands of the spectral image cube along with visual inspection of the large scale colour image showed that the map was not fully planned at the beginning but rather painted in stages, at times by trial and error and that it was unfinished. A new hypothesis for the origin of the Selden map in Aceh Sumatra is proposed based on the new evidences

Tumor Antigen Acrosin Binding Protein Normalizes Mitotic Spindle Function to Promote Cancer Cell Proliferation

Cancer cells manage to divide in the context of gross chromosomal abnormalities. These abnormalities can promote bypass of normal restraints on cell proliferation, but at a cost of mitotic vulnerabilities that can be attacked by chemotherapy. Determining how cancer cells balance these issues may permit chemotherapeutic sensitivity to be leveraged more efficiently. From a pan-genomic siRNA screen for modifiers of chemoresponsiveness, we identified the tumor antigen ACRBP/OY-TES-1 as a specifier of paclitaxel resistance. ACRBP expression is normally restricted to the testes but detected in a wide variety of cancers, including most ovarian cancers. We found that ACRBP is both necessary and sufficient for paclitaxel resistance in ovarian cancer cell lines and ovarian tumor explants. Moreover, high ACRBP expression correlated with reduced survival time and faster relapse among ovarian cancer patients. We identified the mitotic spindle protein NuMA as an ACRBP-interacting protein that could account for the effects of ACRBP on paclitaxel sensitivity. In cancer cells, ACRBP restricted a NuMA-dependent abrogation of mitotic spindle assembly that is otherwise pathologic. As a consequence, ACRBP depletion resulted in mitotic errors and reduced proliferative fitness that could be rescued by NuMA co-depletion. We propose that the co-dependent relationship of ACRBP and NuMA in cancer cells reflects their passage through a selection bottleneck during tumor evolution, one which requires the acquisition of traits which normalize mitotic perturbations that originally drove the plasticity of a pre-neoplastic genome. The molecular definition of such traits as defined by the ACRBP-NuMA complex may represent conceptually ideal intervention targets, based on the wide therapeutic windows they may offer