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.

Primary students’ interpretation of maps : gesture use and mapping knowledge

Maps are used to represent three-dimensional space and are integral to a range of everyday experiences. They are increasingly used in mathematics, being prominent both in school curricula and as a form of assessing students understanding of mathematics ideas. In order to successfully interpret maps, students need to be able to understand that maps: represent space, have their own perspective and scale, and their own set of symbols and texts. Despite the fact that maps have an increased prevalence in society and school, there is evidence to suggest that students have difficulty interpreting maps. This study investigated 43 primary-aged students’ (aged 9-12 years) verbal and gestural behaviours as they engaged with and solved map tasks. Within a multiliteracies framework that focuses on spatial, visual, linguistic, and gestural elements, the study investigated how students interpret map tasks. Specifically, the study sought to understand students’ skills and approaches used to solving map tasks and the gestural behaviours they utilised as they engaged with map tasks. The investigation was undertaken using the Knowledge Discovery in Data (KDD) design. The design of this study capitalised on existing research data to carry out a more detailed analysis of students’ interpretation of map tasks. Video data from an existing data set was reorganised according to two distinct episodes—Task Solution and Task Explanation—and analysed within the multiliteracies framework. Content Analysis was used with these data and through anticipatory data reduction techniques, patterns of behaviour were identified in relation to each specific map task by looking at task solution, task correctness and gesture use. The findings of this study revealed that students had a relatively sound understanding of general mapping knowledge such as identifying landmarks, using keys, compass points and coordinates. However, their understanding of mathematical concepts pertinent to map tasks including location, direction, and movement were less developed. Successful students were able to interpret the map tasks and apply relevant mathematical understanding to navigate the spatial demands of the map tasks while the unsuccessful students were only able to interpret and understand basic map conventions. In terms of their gesture use, the more difficult the task, the more likely students were to exhibit gestural behaviours to solve the task. The most common form of gestural behaviour was deictic, that is a pointing gesture. Deictic gestures not only aided the students capacity to explain how they solved the map tasks but they were also a tool which assisted them to navigate and monitor their spatial movements when solving the tasks. There were a number of implications for theory, learning and teaching, and test and curriculum design arising from the study. From a theoretical perspective, the findings of the study suggest that gesturing is an important element of multimodal engagement in mapping tasks. In terms of teaching and learning, implications include the need for students to utilise gesturing techniques when first faced with new or novel map tasks. As students become more proficient in solving such tasks, they should be encouraged to move beyond a reliance on such gesture use in order to progress to more sophisticated understandings of map tasks. Additionally, teachers need to provide students with opportunities to interpret and attend to multiple modes of information when interpreting map tasks.

Postural balance under normal and altered sensory conditions in normal-weight and overweight children

Background Little or no research has been done in the overweight child on the relative contribution of multisensory information to maintain postural stability. Therefore, the purpose of this study was to investigate postural balance control under normal and experimentally altered sensory conditions in normal-weight versus overweight children. Methods Sixty children were stratified into a younger (7–9 yr) and an older age group (10–12 yr). Participants were also classified as normal-weight (n = 22) or overweight (n = 38), according to the international BMI cut-off points for children. Postural stability was assessed during quiet bilateral stance in four sensory conditions (eyes open or closed, normal or reduced plantar sensation), using a Kistler force plate to quantify COP dynamics. Coefficients of variation were calculated as well to describe intra-individual variability. Findings Removal of vision resulted in systematically higher amounts of postural sway, but no significant BMI group differences were demonstrated across sensory conditions. However, under normal conditions lower plantar cutaneous sensation was associated with higher COP velocities and maximal excursion of the COP in the medial-lateral direction for the overweight group. Regardless of condition, higher variability was shown in the overweight children within the 7–9 yr old subgroup for postural sway velocity, and more specifically medial–lateral velocity. Interpretation In spite of these subtle differences, results did not establish any clear underlying sensory organization impairments that may affect standing balance performance in overweight children compared to normal-weight peers. Consequently, it is believed that other factors account for overweight children's functional balance deficiencies.

Evangeline Series : An interpretation of Classic Gothic Lolita

This series comprises three artefacts described below: Evangeline: Classic Gothic Lolita [3 piece garment]. Evangeline 2: Classic Gothic Lolita Pullip Doll Costume [2 piece garment]. Evangeline 3: Classic Gothic Lolita Mini Pullip Doll Costume [3 piece garment]. The series was part of an exhibition curated by Kathryn Hardy Bernal entitled: "Loli-Pop: A downtown Auckland view on Japanese street fashion". The exhibition explored the connections between gothic lolita fashion and popular culture. This work reflects on the aspect of collections in respect of the work of Hardy Bernal in relation to the connection between the japanese classic gothic lolita and the doll culture surrounding the movement. The pieces are interconnected and intended to communicate these aspects through a doll like dress worn by a model (Evangeline 1], carrying a doll wearing the same dress [Evangeline 2], carrying a smaller doll again wearing the same dress [Evangeline 3]. The artefacts appeared appeared as a central piece in the exhibition which was held at the War Memorial Museum in Auckland, New Zealand (15 September - 25 November 2007).

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.

A Stochastic View of Optimal Regret through Minimax Duality

We study the regret of optimal strategies for online convex optimization games. Using von Neumann's minimax theorem, we show that the optimal regret in this adversarial setting is closely related to the behavior of the empirical minimization algorithm in a stochastic process setting: it is equal to the maximum, over joint distributions of the adversary's action sequence, of the difference between a sum of minimal expected losses and the minimal empirical loss. We show that the optimal regret has a natural geometric interpretation, since it can be viewed as the gap in Jensen's inequality for a concave functional--the minimizer over the player's actions of expected loss--defined on a set of probability distributions. We use this expression to obtain upper and lower bounds on the regret of an optimal strategy for a variety of online learning problems. Our method provides upper bounds without the need to construct a learning algorithm; the lower bounds provide explicit optimal strategies for the adversary. Peter L. Bartlett, Alexander Rakhlin

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.