875 resultados para Chromatid breaks


Relevância:

10.00% 10.00%

Publicador:

Resumo:

Cultural theory breaks with Modern analysis by rejecting traditional notions of race, gender, class and sexuality. In doing so, alternative frameworks such as Post-Feminism emerge which are useful for thinking about culture, technology and what our interactions with it mean. From a Post-Feminist perspective it can be seen how in our multi-cultural, post-industrial, digitized world, there is space to move beyond traditional ways of dividing up society such as ‘male’ and ‘female’. We are then free to re-construct our identity in light of a rich diversity of individually relevant experiences. Therefore, in order to get a better understanding of the highly nuanced cultural interactions that characterize our use of technology, this paper argues against using the inherently stereotyped lens of gender and allowing a new set of user needs to emerge.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

A simple mathematical model is presented to describe the cell separation process that plants undertake in order to deliberately shed organs. The focus here is on modelling the production of the enzyme polygalacturonase, which breaks down pectin that provides natural cell-to-cell adhesion in the localised abscission zone. A coupled system of three ordinary differential equations is given for a single cell, and then extended to hold for a layer of cells in the abscission zone. Simple observations are made based on the results of this preliminary model and, furthermore, a number of opportunities for applied mathematicians to make contributions in this subject area are discussed.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Background: In order to maintain cellular viability and genetic integrity cells must respond quickly following the induction of cytotoxic double strand DNA breaks (DSB). This response requires a number of processes including stabilisation of the DSB, signalling of the break and repair. It is becoming increasingly apparent that one key step in this process is chromatin remodelling. Results: Here we describe the chromodomain helicase DNA-binding protein (CHD4) as a target of ATM kinase. We show that ionising radiation (IR)-induced phosphorylation of CHD4 affects its intranuclear organization resulting in increased chromatin binding/retention. We also show assembly of phosphorylated CHD4 foci at sites of DNA damage, which might be required to fulfil its function in the regulation of DNA repair. Consistent with this, cells overexpressing a phospho-mutant version of CHD4 that cannot be phosphorylated by ATM fail to show enhanced chromatin retention after DSBs and display high rates of spontaneous damage. Conclusion: These results provide insight into how CHD4 phosphorylation might be required to remodel chromatin around DNA breaks allowing efficient DNA repair to occur.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Damage to genetic material represents a persistent and ubiquitous threat to genomic stability. Once DNA damage is detected, a multifaceted signaling network is activated that halts the cell cycle, initiates repair, and in some instances induces apoptotic cell death. In this article, we will review DNA damage surveillance networks, which maintain the stability of our genome, and discuss the efforts underway to identify chemotherapeutic compounds targeting the core components of DNA double-strand breaks (DSB) response pathway. The majority of tumor cells have defects in maintaining genomic stability owing to the loss of an appropriate response to DNA damage. New anticancer agents are exploiting this vulnerability of cancer cells to enhance therapeutic indexes, with limited normal tissue toxicity. Recently inhibitors of the checkpoint kinases Chk1 and Chk2 have been shown to sensitize tumor cells to DNA damaging agents. In addition, the treatment of BRCA1- or BRCA2-deficient tumor cells with poly(ADP-ribose) polymerase (PARP) inhibitors also leads to specific tumor killing. Due to the numerous roles of p53 in genomic stability and its defects in many human cancers, therapeutic agents that restore p53 activity in tumors are the subject of multiple clinical trials. In this article we highlight the proteins mentioned above and catalog several additional players in the DNA damage response pathway, including ATM, DNA-PK, and the MRN complex, which might be amenable to pharmacological interventions and lead to new approaches to sensitize cancer cells to radio- and chemotherapy. The challenge is how to identify those patients most receptive to these treatments.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Single-strand DNA (ssDNA)-binding proteins (SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair1. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand-exchange proteins, activating transcription and mediating protein–protein interactions. In eukaryotes, the major SSB, replication protein A (RPA), is a heterotrimer1. Here we describe a second human SSB (hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell-cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S-phase cells and hSSB1 deficiency does not influence S-phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse endpoints in the cellular DNA damage response.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Homologous recombinational repair is an essential mechanism for repair of double-strand breaks in DNA. Recombinases of the RecA-fold family play a crucial role in this process, forming filaments that utilize ATP to mediate their interactions with singleand double-stranded DNA. The recombinase molecules present in the archaea (RadA) and eukaryota (Rad51) are more closely related to each other than to their bacterial counterpart (RecA) and, as a result, RadA makes a suitable model for the eukaryotic system. The crystal structure of Sulfolobus solfataricus RadA has been solved to a resolution of 3.2 A° in the absence of nucleotide analogues or DNA, revealing a narrow filamentous assembly with three molecules per helical turn. As observed in other RecA-family recombinases, each RadA molecule in the filament is linked to its neighbour via interactions of a short b-strand with the neighbouring ATPase domain. However, despite apparent flexibility between domains, comparison with other structures indicates conservation of a number of key interactions that introduce rigidity to the system, allowing allosteric control of the filament by interaction with ATP. Additional analysis reveals that the interaction specificity of the five human Rad51 paralogues can be predicted using a simple model based on the RadA structure.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

This volume breaks new ground by approaching Socially Responsible Investment (SRI) as an explicitly ethical practice in financial markets. The work explains the philosophical and practical shortcomings of ‘long term shareholder value’ and the origins and conceptual structure of SRI, and links its pursuit to both its deeper philosophical foundations and the broader, multi-dimensional global movement towards greater social responsibility in global markets. Interviews with fund managers in the Australian SRI sector generate recommendations for better integrating ethics into SRI practice via ethically informed engagement with invested companies, and an in-depth discussion of the central practical SRI issue of fiduciary responsibility strengthens the case in favour of SRI. The practical and ethical theoretical perspectives are then brought together to sketch out an achievable ideal for SRI worldwide, in which those who are involved in investment and business decisions become part of an ‘ethical chain’ of decision makers linking the ultimate owners of capital with the business executives who frame, advocate and implement business strategies. In between there are investment advisors, fund managers, business analysts and boards. The problem lies in the fact that the ultimate owners are discouraged from considering their own values, or even their own long term interests, whilst the others often look only to short term interests. The solution lies in the latter recognising themselves as links in the ethical chain.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Purpose – The purpose of this paper is to determine the patterns of transitional employment (TE) aspirations and training and development (T&D) needs of women within local government. Design/methodology/approach – A quantitative survey methodology was used to identify aspirations in a sample of 1,068 employees from the Australian Local Government Association. Findings – Mature-aged women were very interested in continuous learning at work despite their limited formal education. Their training preferences consisted of informal delivery face-to-face or online in the areas of management or administration. Younger women were interested in undertaking university courses, while a minority were interested in blue collar occupations. Practical implications – Through the identification of patterns of TE and T&D aspirations, long term strategies to develop and retain women in local government may be developed. Findings suggest that mature-aged women would benefit from additional T&D to facilitate entry into management and senior administration positions, as well as strategies to facilitate a shift in organizational climate. Social implications – Mature-aged women were found to be a potentially untapped resource for management and senior administrative roles owing to their interest in developing skills in these fields and pursuing TE. Younger women may also benefit from T&D to maintain their capacity during breaks from employment. Encouragement of women in non-traditional areas may also address skill shortages in the local government. Originality/value – Mature-aged women were found to be a potentially untapped resource for management and senior administrative roles owing to their interest in developing skills in these fields and pursuing TE. Younger women may also benefit from T&D to maintain their capacity during breaks from employment. Encouragement of women in non-traditional areas may also address skill shortages in the local government.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Evasive change-of-direction manoeuvres (agility skills) are a fundamental ability in rugby union. In this study, we explored the attributes of agility skill execution as they relate to effective attacking strategies in rugby union. Seven Super 14 games were coded using variables that assessed team patterns and individual movement characteristics during attacking ball carries. The results indicated that tackle-breaks are a key determinant of try-scoring ability and team success in rugby union. The ability of the attacking ball carrier to receive the ball at high speed with at least two body lengths from the defence line against an isolated defender promoted tackle-breaks. Furthermore, the execution of a side-step evasive manoeuvre at a change of direction angle of 20–60° and a distance of one to two body lengths from the defence, and then straightening the running line following the initial direction change at an angle of 20–60°, was associated with tackle-breaks. This study provides critical insight regarding the attributes of agility skill execution that are associated with effective ball carries in rugby union.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

This project involved the complete refurbishment and extension of a 1980’s two-storey domestic brick building, previously used as a Boarding House (Class 3), into Middle School facilities (Class 9b) on a heritage listed site at Nudgee College secondary school, Brisbane. The building now accommodates 12 technologically advanced classrooms, computer lab and learning support rooms, tuckshop, art room, mini library/reading/stage area, dedicated work areas for science and large projects with access to water on both floors, staff facilities and an undercover play area suitable for assemblies and presentations. The project was based on a Reggio Emilia approach, in which the organisation of the physical environment is referred to as the child’s third teacher, creating opportunities for complex, varied, sustained and changing relationships between people and ideas. Classrooms open to a communal centre piazza and are integrated with the rest of the school and the school with the surrounding community. In order to achieve this linkage of the building with the overall masterplan of the site, a key strategy of the internal planning was to orientate teaching areas around a well defined active circulation space that breaks out of the building form to legibly define the new access points to the building and connect up to the pathway network of the campus. The width of the building allowed for classrooms and a generous corridor that has become ‘breakout’ teaching areas for art, IT, and small group activities. Large sliding glass walls allow teachers to maintain supervision of students across all areas and allow maximum light penetration through small domestic window openings into the deep and low-height spaces. The building was also designed with an effort to uphold cultural characteristics from the Edmund Rice Education Charter (2004). Coherent planning is accompanied by a quality fit-out, creating a vibrant and memorable environment in which to deliver the upper primary curriculum. Consistent with the Reggio Emilia approach, materials, expressive of the school’s colours, are used in a contemporary, adventurous manner to create panels of colour useful for massing and defining the ‘breakout’ teaching areas and paths of travel, and storage elements are detailed and arranged to draw attention to their aesthetic features. Modifications were difficult due to the random placement of load bearing walls, minimum ceiling heights, the general standard of finishes and new fire and energy requirements, however the reuse of this building was assessed to be up to 30% cheaper than an equivalent new building, The fit out integrates information technology and services at a level not usually found in primary school facilities. This has been achieved within the existing building fabric through thoughtful detailing and co-ordination with allied disciplines.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The head direction (HD) system in mammals contains neurons that fire to represent the direction the animal is facing in its environment. The ability of these cells to reliably track head direction even after the removal of external sensory cues implies that the HD system is calibrated to function effectively using just internal (proprioceptive and vestibular) inputs. Rat pups and other infant mammals display stereotypical warm-up movements prior to locomotion in novel environments, and similar warm-up movements are seen in adult mammals with certain brain lesion-induced motor impairments. In this study we propose that synaptic learning mechanisms, in conjunction with appropriate movement strategies based on warm-up movements, can calibrate the HD system so that it functions effectively even in darkness. To examine the link between physical embodiment and neural control, and to determine that the system is robust to real-world phenomena, we implemented the synaptic mechanisms in a spiking neural network and tested it on a mobile robot platform. Results show that the combination of the synaptic learning mechanisms and warm-up movements are able to reliably calibrate the HD system so that it accurately tracks real-world head direction, and that calibration breaks down in systematic ways if certain movements are omitted. This work confirms that targeted, embodied behaviour can be used to calibrate neural systems, demonstrates that ‘grounding’ of modeled biological processes in the real world can reveal underlying functional principles (supporting the importance of robotics to biology), and proposes a functional role for stereotypical behaviours seen in infant mammals and those animals with certain motor deficits. We conjecture that these calibration principles may extend to the calibration of other neural systems involved in motion tracking and the representation of space, such as grid cells in entorhinal cortex.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Flexible work practices spreading work times across the entire week have reduced the time to engage in leisure activities and for some have compounded the problem of a lack of defined break between work weeks. This study examines time spent outside of the workplace through a multiple case study of working time and leisure in the construction industry. A framework of synchronous leisure is used to examine the interplay of work and non-work arrangements. The effects of changing work arrangements to deliver a longer break between working weeks and the consequent impact on leisure activities are analysed. Interviews and focus groups across four construction sites revealed that while leisure is important to relieve fatigue and overwork, a work schedule allowing a long break between working weeks, specifically on a weekend, enables workers to achieve synchronous time, particularly with family, and improves work-life balance satisfaction. It was found that a well-defined break across a weekend also offers the opportunity to synchronize schedules with others to spend time away on short breaks.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Book summary: In a constantly evolving context of performance management, accountability and risk assessment, police organisations and frontline police officers are required to pay careful attention to what has come to be known as ‘at risk people’, ‘vulnerable populations’ or ‘vulnerable people’. Vulnerable people have become a key focus of policy. Concurrently, there have been stronger demands on police, and a steep increase in police powers in relation to their interaction with vulnerable people. The premise of this protectionist and interventionist agenda is threefold: to protect the rights of vulnerable individuals proactively cater for their vulnerability within the justice system; and to secure police operations and protocols within strict guidelines. This collection unpacks ‘vulnerable people policing’ in theory and practice and guides the reader through the policing process as it is experienced by police officers, victims, offenders, witnesses and justice stakeholders. Each chapter features a single step of the policing process: from police recruit education through to custody, and the final transfer of vulnerable people to courts and sentencing. This edited collection provides analytical, theoretical and empirical insights on vulnerable people policing, and reflects on critical issues in a domain that is increasingly subject to speedy conversion from policy to practice, and heightened media and political scrutiny. It breaks down policing practices, operations and procedures that have vulnerable populations as a focus, bringing together original and innovative academic research and literature, practitioner experience and discussion of policy implications (from local and international perspectives). The particular nature of this collection highlights the multi-disciplinary nature of police work, sheds light on how specific, mandatory policies guide police officers steps in their interaction with vulnerable populations, and discusses the practicalities of police decision making at key points in this process.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Background: Radiation-induced skin reaction (RISR) is one of the most common and distressing side effects of radiotherapy in patients with cancer. It is featured with swelling, redness, itching, pain, breaks in skin, discomfort, and a burning sensation. There is a lack of convincing evidence supporting any single practice in the prevention or management of RISR. Methods/Designs: This double-blinded randomised controlled trial aims to investigate the effects of a natural oil-based emulsion containing allantoin (as known as Moogoo Udder Cream®) versus aqueous cream in reducing RISR, improving pain, itching and quality of life in this patient group. One group will receive Moogoo Udder Cream®. Another group will receive aqueous cream. Outcome measures will be collected using patient self-administered questionnaire, interviewer administered questionnaire and clinician assessment at commencement of radiotherapy, weekly during radiotherapy, and four weeks after the completion of radiotherapy. Discussion: Despite advances of radiologic advances and supportive care, RISR are still not well managed. There is a lack of efficacious interventions in managing RISR. While anecdotal evidence suggests that Moogoo Udder Cream® may be effective in managing RISR, research is needed to substantiate this claim. This paper presents the design of a double blind randomised controlled trial that will evaluate the effects of Moogoo Udder Cream® versus aqueous cream for managing in RISR in patients with cancer. Trial registration: ACTRN 12612000568819

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The DNA damage response encompasses a complex series of signaling pathways that function to regulate and facilitate the repair of damaged DNA. Recent studies have shown that the repair of transcriptionally inactive chromatin, named heterochromatin, is dependent upon the phosphorylation of the co-repressor, Krüppel-associated box (KRAB) domain-associated protein (KAP-1), by the ataxia telangiectasia-mutated (ATM) kinase. Co-repressors, such as KAP-1, function to regulate the rigid structure of heterochromatin by recruiting histone-modifying enzymes, such HDAC1/2, SETDB1, and nucleosome-remodeling complexes such as CHD3. Here, we have characterized a phosphorylation site in the HP1-binding domain of KAP-1, Ser-473, which is phosphorylated by the cell cycle checkpoint kinase Chk2. Expression of a nonphosphorylatable S473A mutant conferred cellular sensitivity to DNA-damaging agents and led to defective repair of DNA double-strand breaks in heterochromatin. In addition, cells expressing S473A also displayed defective mobilization of the HP1-β chromodomain protein. The DNA repair defect observed in cells expressing S473A was alleviated by depletion of HP1-β, suggesting that phosphorylation of KAP-1 on Ser-473 promotes the mobilization of HP1-β from heterochromatin and subsequent DNA repair. These results suggest a novel mechanism of KAP-1-mediated chromatin restructuring via Chk2-regulated HP1-β exchange from heterochromatin, promoting DNA repair.