332 resultados para DNA-damaging activities


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Previous studies showed that a significant number of the particles present in indoor air are generated by cooking activities, and measured particle concentrations and exposures have been used to estimate the related human dose. The dose evaluation can be affected by the particle charge level which is usually not considered in particle deposition models. To this purpose, in this paper we show, for the very first time, the electric charge of particles generated during cooking activities and thus extending the interest on particle charging characterization to indoor micro-environments, so far essentially focused on outdoors. Particle number, together with positive and negative cluster ion concentrations, was monitored using a condensation particle counter and two air ion counters, respectively, during different cooking events. Positively-charged particle distribution fractions during gas combustion, bacon grilling, and eggplant grilling events were measured by two Scanning Mobility Particle Sizer spectrometers, used with and without a neutralizer. Finally, a Tandem Differential Mobility Analyzer was used to measure the charge specific particle distributions of bacon and eggplant grilling experiments, selecting particles of 30, 50, 80 and 100 nm in mobility diameter. The total fraction of positively-charged particles was 4.0%, 7.9%, and 5.6% for gas combustion, bacon grilling, and eggplant grilling events, respectively, then lower than other typical outdoor combustion-generated particles.

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This thesis provides the first inquiry into the use of creative activities in dementia care in residential aged care facilities in Australia. The study used descriptive method design, incorporating a mix of quantitative and qualitative approaches to explore the incidence and the characteristics of these activities from the carers' perspective. Information about the use of creative activities and the appreciation of these activities by residents and carers is essential to the provision of dementia care and treatment to improve the quality of life of people with dementia.

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Epigenetic changes correspond to heritable modifications of the chromatin structure, which do not involve any alteration of the DNA sequence but nonetheless affect gene expression. These mechanisms play an important role in cell differentiation, but aberrant occurrences are also associated with a number of diseases, including cancer and neural development disorders. In particular, aberrant DNA methylation induced by H. Pylori has been found to be a significant risk factor in gastric cancer. To investigate the sensitivity of different genes and cell types to this infection, a computational model of methylation in gastric crypts is developed. In this article, we review existing results from physical experiments and outline their limitations, before presenting the computational model and investigating the influence of its parameters.

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Over the last few years, investigations of human epigenetic profiles have identified key elements of change to be Histone Modifications, stable and heritable DNA methylation and Chromatin remodeling. These factors determine gene expression levels and characterise conditions leading to disease. In order to extract information embedded in long DNA sequences, data mining and pattern recognition tools are widely used, but efforts have been limited to date with respect to analyzing epigenetic changes, and their role as catalysts in disease onset. Useful insight, however, can be gained by investigation of associated dinucleotide distributions. The focus of this paper is to explore specific dinucleotides frequencies across defined regions within the human genome, and to identify new patterns between epigenetic mechanisms and DNA content. Signal processing methods, including Fourier and Wavelet Transformations, are employed and principal results are reported.

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Deoxyribonucleic acid molecules are heralding a new generation of reverse - engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display non-toxicity and are simpler to develop. This presentation will discuss the potential applications of pDNA molecules in vaccine development and gene therapy, pilot-scale production of pDNA-based biopharmaceuticals and the controlled delivery of therapeutic sequences in biodegradable polymers to different target cells via the nasal route.

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The monitoring of the actual activities of daily living of individuals with lower limb amputation is essential for an evidence-based fitting of the prosthesis, more particularly the choice of components (e.g., knees, ankles, feet)[1-4]. The purpose of this presentation was to give an overview of the categorization of the load regime data to assess the functional output and usage of the prosthesis of lower limb amputees has presented in several publications[5, 6]. The objectives were to present a categorization of load regime and to report the results for a case.

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One way to consider Technology as other than an add-on might be to consider the opportunities to learn literacies opened by participation in technology. In this commentary Vinesh Chandra considers this in light of robotics lessons with primary school students as part of his work in the UR Learning project.

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This work brings a perspective from an employer-sponsored health and wellness program called Global Corporate Challenge (GCC) to the 'quantified self' research. We present preliminary findings from a study with 17 university employees who participated in the GCC. We aimed to explore how participants derived meaningfulness from their self-tracking experiences. Our findings echo the growing body of work that advocates for conceptualizing activity tracking beyond the rationalistic, data-oriented perspectives and supporting more social and lived experiences.

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This paper investigates the motivations of young adults aged 18 to 24 years to participate in physical activities and how technology might best support this motivation. Motivational factors were studied through contextual interviews, an adapted cultural probe activity and a survey with a group of young adults currently active in sports. From our preliminary findings we determine that staying healthy, achieving specific goals and socialising represent key motivational factors for young adults to be active in sports, but also, that exercise is not considered a high priority in their daily lives. A link between the motivation of achieving specific goals and a technology to measure and track activities was established. The study concludes with three implications for the design of technology to motivate young adults to participate in sports.

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This research utilised data from The Longitudinal Study of Australian Children and explored continuity and change in parental engagement in home learning activities with young children. The findings indicated a decrease over time in parental engagement with children, from age to 2-3 years to 6-7 years. Rate of decrease impacted negatively on learning outcomes for language and literacy, and mathematical thinking, in the early years of school, when children were aged 6-7 years. Shared reading with children and interactions around everyday home activities and play, in which children and parents participate together, impact on children's later development.

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This pilot study aimed to assess the feasibility and acceptability of a Behavioral Activities intervention (BE-ACTIV) in Australian nursing homes. BE-ACTIV was developed by researchers at the University of Louisville, USA, to improve mood and quality of life (QOL) in nursing home residents with mild to moderate dementia. An 8-week trial was conducted and 10 residents with mild to moderate dementia received the BE-ACTIV intervention while 8 residents received a Walking and Talking intervention. Measures of depression (GDS–12R), and QOL (QOL-AD-NH) were administered prior to and following the interventions. Qualitative feedback indicated residents benefited from BE-ACTIV, evident by improved mood, although no statistically significant treatment effect was found. Moreover, the intervention was found to be feasible and acceptable to Australian nursing home staff and our findings highlight the importance of individualizing activities for people with dementia, of which 1:1 staff attention was a key component.

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Cisplatin (cis-diamminedichloroplatinum (II)), is a platinum based chemotherapeutic employed in the clinic to treat patients with lung, ovarian, colorectal or head and neck cancers. Cisplatin acts to induce tumor cell death via multiple mechanisms. The best characterized mode of action is through irreversible DNA cross-links which activate DNA damage signals leading to cell death via the intrinsic mitochondrial apoptosis pathway. However, the primary issue with cisplatin is that while patients initially respond favorably, sustained cisplatin therapy often yields chemoresistance resulting in therapeutic failure. In this chapter, we review the DNA damage and repair pathways that contribute to cisplatin resistance. We also examine the cellular implications of cisplatin resistance that may lead to selection of subpopulations of cells within a tumor. In better understanding the mechanisms conferring cisplatin resistance, novel targets may be identified to restore drug sensitivity.

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Germline mutations in BRCA1 predispose carriers to a high incidence of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through critical roles in DNA repair, cell cycle arrest and transcriptional control. A major question has been why BRCA1 loss or mutation leads to tumors mainly in estrogen-regulated tissues, given that BRCA1 has essential functions in all cell types. Here we report that estrogen and estrogen metabolites can cause DNA double strand breaks (DSB) in estrogen receptor-α negative breast cells and that BRCA1 is required to repair these DSBs to prevent metabolite-induced genomic instability. We found that BRCA1 also regulates estrogen metabolism and metabolite-mediated DNA damage by repressing the transcription of estrogen-metabolising enzymes, such as CYP1A1, in breast cells. Lastly, we used a knock-in human cell model with a heterozygous BRCA1 pathogenic mutation to show how BRCA1 haploinsufficiency affects these processes. Our findings provide pivotal new insights into why BRCA1 mutation drives the formation of tumours in estrogen-regulated tissues, despite the general role of BRCA1 in DNA repair in all cell types.

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Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

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Canonical single-stranded DNA-binding proteins (SSBs) from the oligosaccharide/oligonucleotide-binding (OB) domain family are present in all known organisms and are critical for DNA replication, recombination and repair. The SSB from the hyperthermophilic crenarchaeote Sulfolobus solfataricus (SsoSSB) has a ‘simple’ domain organization consisting of a single DNA-binding OB fold coupled to a flexible C-terminal tail, in contrast with other SSBs in this family that incorporate up to four OB domains. Despite the large differences in the domain organization within the SSB family, the structure of the OB domain is remarkably similar all cellular life forms. However, there are significant differences in the molecular mechanism of ssDNA binding. We have determined the structure of the SsoSSB OB domain bound to ssDNA by NMR spectroscopy. We reveal that ssDNA recognition is modulated by base-stacking of three key aromatic residues, in contrast with the OB domains of human RPA and the recently discovered human homologue of SsoSSB, hSSB1. We also demonstrate that SsoSSB binds ssDNA with a footprint of five bases and with a defined binding polarity. These data elucidate the structural basis of DNA binding and shed light on the molecular mechanism by which these ‘simple’ SSBs interact with ssDNA.