Multiple human single-stranded DNA binding proteins function in genome maintenance : structural, biochemical and functional analysis

DNA exists predominantly in a duplex form that is preserved via specific base pairing. This base pairing affords a considerable degree of protection against chemical or physical damage and preserves coding potential. However, there are many situations, e.g. during DNA damage and programmed cellular processes such as DNA replication and transcription, in which the DNA duplex is separated into two singlestranded DNA (ssDNA) strands. This ssDNA is vulnerable to attack by nucleases, binding by inappropriate proteins and chemical attack. It is very important to control the generation of ssDNA and protect it when it forms, and for this reason all cellular organisms and many viruses encode a ssDNA binding protein (SSB). All known SSBs use an oligosaccharide/oligonucleotide binding (OB)-fold domain for DNA binding. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating strand-exchange proteins and helicases, and mediation of protein–protein interactions. Recently two additional human SSBs have been identified that are more closely related to bacterial and archaeal SSBs. Prior to this it was believed that replication protein A, RPA, was the only human equivalent of bacterial SSB. RPA is thought to be required for most aspects of DNA metabolism including DNA replication, recombination and repair. This review will discuss in further detail the biological pathways in which human SSBs function.

Physical and functional interaction of the archaeal single-stranded DNA-binding protein SSB with RNA polymerase

Archaeal transcription utilizes a complex multisubunit RNA polymerase and the basal transcription factors TBP and TF(II)B, closely resembling its eukaryal counterpart. We have uncovered a tight physical and functional interaction between RNA polymerase and the single-stranded DNA-binding protein SSB in Sulfolobus solfataricus. SSB stimulates transcription from promoters in vitro under TBP-limiting conditions and supports transcription in the absence of TBP. SSB also rescues transcription from repression by reconstituted chromatin. We demonstrate the potential for promoter melting by SSB, suggesting a plausible basis for the stimulation of transcription. This stimulation requires both the single-stranded DNA-binding domain and the acidic C-terminal tail of the SSB. The tail forms a stable interaction with RNA polymerase. These data reveal an unexpected role for single-stranded DNA-binding proteins in transcription in archaea.

Inferior visual field reductions are associated with poorer functional status among older adults with glaucoma

Purpose: To examine the relationship between visual impairment and functional status in a community-dwelling sample of older adults with glaucoma. Methods: This study included 74 community-dwelling older adults with open-angle glaucoma (aged 74 ± 6 years). Assessment of central vision included high-contrast visual acuity and Pelli-Robson contrast sensitivity. Binocular integrated visual fields were derived from merged monocular Humphrey Field Analyser visual field plots. Functional status outcome measures included physical performance tests (6-min walk test, timed up and go test and lower limb strength), a physical activity questionnaire (Physical Activity Scale for the Elderly) and an overall functional status score. Correlation and linear regression analyses, adjusting for age and gender, examined the association between visual impairment and functional status outcomes. Results: Greater levels of visual impairment were significantly associated with lower levels of functional status among community-dwelling older adults with glaucoma, independent of age and gender. Specifically, lower levels of visual function were associated with slower timed up and go performance, weaker lower limb strength, lower self-reported physical activity, and lower overall functional status scores. Of the components of vision examined, the inferior visual field and contrast factors were the strongest predictors of these functional outcomes, whereas the superior visual field factor was not related to functional status. Conclusions: Greater visual impairment, particularly in the inferior visual field and loss of contrast sensitivity, was associated with poorer functional status among older adults with glaucoma. The findings of this study highlight the potential links between visual impairment and the onset of functional decline. Interventions which promote physical activity among older adults with glaucoma may assist in preventing functional decline, frailty and falls, and improve overall health and well-being.

Adapting, renewing, subverting : what place the performing arts in the creative industries?

Creative Industries was adopted as a platform in the 90s by the Blair government in the UK to describe the convergence of the arts, media, communication and information technologies as a newly formed cluster, providing economic and cultural capital for the knowledge economy. The philosophy and rhetoric which has grown around this concept (Leadbeater 2000, Castells 2000, Florida 2000, Caves 2000, Hartley 2000) has been influential in re-contextualising culture and the arts in the 21st century. Where governments and educational institutions have embraced the context of the creative industries, it is having a profound effect on the way arts are being positioned, originally as ‘creative content’ for the new economy. Countries and regions which have actively targeted the Creative Industries as an important economic growth factor in a post-industrial environment are numerous, but it is interesting to note that North and South East Asia and Australia have been at the forefront of developing the Creative Industries in its various guises. It could be argued that the initial phase of Creative Industries concentrated on media and communication technologies to provide commercial outcomes in small incubator business models; developing, for example, products for the games industry. Creative Industries is now entering a second phase of development; one in which the broader palette of the arts, though still not at the forefront of debate, is being re-examined. Both phases of Creative Industries have emphasised creativity and innovation as key drivers in the success and effectiveness of this sector, and although the arts by no means has a monopoly on these drivers, it is where they have an important part to play in the creative industries context. Arguably, the second wave of the creative industries acknowledges to a greater extent that commercialisation works in tandem with government and other support in a complex mixed economic model. In relation to the performing arts, the global market has seen an increase in large-scale cultural events such as festivals which are providing employment for the arts industry and multiplier effects in other parts of the economy. Differentiated product is important in this competitive arena and the use of mediated and digitised environments has been able to increase the amount of arts product available to an international market. This changed environment requires the development of new skills for our artists and producers and has given rise to a reappraisal of approaches to arts training and research in the Higher Degree Education sector (Brown 2007, Cunningham 2006). This paper examines pedagogical changes which took place in the first Creative Industries Faculty in the world at Queensland University of Technology as well as the increased opportunities for leading research initiatives. It concludes with the example of an interdisciplinary artwork produced in a creative industries precinct, exemplifying the convergence of arts and communication technologies and that of artistic practice and research.

Performing the unutterable : mapping the experiential in contemporary dance

This research project looks to engage audiences in a variety of experiential ways by reexamining and manipulating the traditional presentation paradigm for viewing Western contemporary dance. It considers how the audience may be situated in the creation and presentation of contemporary dance generally, and specifically in the work The Voyeur, which researched these issues in action. By situating the body of the audience member as a site of understanding and meaning making, this practice-based research considers the audience within the artists’ creative process from the inception of a creative work, rather than after the work has been created. The research questions how a ‘lived experience’ of contemporary dance could be deepened for the audience. It presents a series of ‘tools’ to create alternative frameworks of presentation that challenge the dominant modes of creation, presentation and meaning making in contemporary dance. The five tools established and applied in this research are: site, liminality, agency, proximity and performer authenticity. These tools are framed as a series of calibrated scales that allow choreographers to map decisions made in the studio in relation to potential audience engagement. These scales have the ability to house multiple presentation formats from the traditional to the avant garde and open up possibilities for broad analysis of a wide range of artistic dance works.

Computing in performing arts education and practice

The performing arts have traditionally made limited use of and showed limited acceptance of computing technology. There are cognitive, physical, environmental, and social influences on the use of computers in performing arts. This paper will examine those influences on the practice of computers in the performing arts and their implications for education in those areas. These implications for the learning environment include infrastructure, interface design, industrial design, and software functionality. Although many of the issues raised in this paper are common to all visual and performing arts, there are significant differences between them which require abstraction of the concepts presented in this paper beyond the more practical focus intended. In particular there are differences in the ways humans are involved in the presentation of a work, and the transitory verses static nature of time in art products.

Functional role of cell surface CUB domain-containing protein 1 in tumour cell dissemination

The function of CUB domain-containing protein 1 (CDCP1), a recently described transmembrane protein expressed on the surface of hematopoietic stem cells and normal and malignant cells of different tissue origin, is not well defined. The contribution of CDCP1 to tumor metastasis was analyzed by using HeLa carcinoma cells overexpressing CDCP1 (HeLa-CDCP1) and a high-disseminating variant of prostate carcinoma PC-3 naturally expressing high levels of CDCP1 (PC3-hi/diss). CDCP1 expression rendered HeLa cells more aggressive in experimental metastasis in immunodeficient mice. Metastatic colonization by HeLa-CDCP1 was effectively inhibited with subtractive immunization-generated, CDCP1-specific monoclonal antibody (mAb) 41-2, suggesting that CDCP1 facilitates relatively late stages of the metastatic cascade. In the chick embryo model, time- and dose-dependent inhibition of HeLa-CDCP1 colonization by mAb 41-2 was analyzed quantitatively to determine when and where CDCP1 functions during metastasis. Quantitative PCR and immunohistochemical analyses indicated that CDCP1 facilitated tumor cell survival soon after vascular arrest. Live cell imaging showed that the function-blocking mechanism of mAb 41-2 involved enhancement of tumor cell apoptosis, confirmed by attenuation of mAb 41-2–mediated effects with the caspase inhibitor z-VAD-fmk. Under proapoptotic conditions in vitro, CDCP1 expression conferred HeLa-CDCP1 cells with resistance to doxorubicin-induced apoptosis, whereas ligation of CDCP1 with mAb 41-2 caused additional enhancement of the apoptotic response. The functional role of naturally expressed CDCP1 was shown by mAb 41-2–mediated inhibition of both experimental and spontaneous metastasis of PC3-hi/diss. These findings confirm that CDCP1 functions as an antiapoptotic molecule and indicate that during metastasis CDCP1 facilitates tumor cell survival likely during or soon after extravasation.