279 resultados para nucleotide repeat


Relevância:

10.00% 10.00%

Publicador:

Resumo:

KPNA3 is a gene that has been linked to schizophrenia susceptibility. In this study we investigated the possible association between KPNA3 variation and schizophrenia. To investigate a wider role of KPNA3 across psychiatric disorders we also analysed major depression, PTSD, nicotine dependent, alcohol dependent and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach we genotyped six KPNA3 single nucleotide polymorphisms (SNPs) in 157 schizophrenia patients, 121 post-traumatic stress disorder patients, 120 opiate dependent patients, 231 alcohol dependent patients, 147 nicotine dependent patients and 266 major depression patients. One SNP rs2273816 was found to be significantly associated with schizophrenia, opiate dependence and alcohol dependence at the genotype and allele level. Major depression was also associated with rs2273816 but only at the allele level. Our study suggests that KPNA3 may contribute to the genetic susceptibility to schizophrenia as well as other psychiatric disorders.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The Akin collection is the outcome of a project to lead, guide and curate a luxury, retail-ready fashion collection from a collaboration between five emerging fashion designers and five established Indigenous artists. Research background There is a history of Indigenous artists in Australia being treated unethically; by misappropriation and misrepresentation of their work, inequity of payment for their creativity and little acknowledgement of their cultural contribution to collaborative fashion product sold globally. This has created an atmosphere of bad press for fashion, as well as a fear for emerging designers to include/collaborate with Indigenous artists for textile prints. This fear has been so intense that many emerging Australian designers are now seeking collaboration with other countries’ Indigenous communities, thus missing out on a rich cultural and diverse aesthetic that could brand a truly unique Australian label in the international marketplace. The fashion brands that have collaborated with Indigenous Australian artists have traditionally been a ONE designer label incorporating Indigenous prints, for collections that have little acknowledgement of the artist’s contribution and strong branding for the label and/or fashion designer. This collection seeks to create an equitable and profitable fashion collection under one brand where all artists and designers receive equal payment, equal promotion/credibility, as well as equal royalties for any garments ordered by retailers. Research question Is it possible to curate an ethical, luxury, retail-ready, international fashion brand with a collaboration of five (5) emerging designers and five (5) Indigenous artists? Research contribution In the fashion industry, existing collaborations for Australian Indigenous artists have been with ONE fashion designer or one existing fashion label. This is the first fashion collection created under one brand name with equal credibility and profits for both artists and designers. The process involved presenting workshops ranging from understanding the logistics and timing of the fashion supply chain, costing of garments, the process of ‘ranging’ fashion product for a collection and creating repeat prints from a specific artwork, ready for digital printing. A workshop was also facilitated so both designer and artist could work together to create (and co-own) unique t shirt prints. Lawyers were consulted and ethical contracts were drawn up to cover all participants in this innovative collaboration. While the collaboration of artist and designer was important, the collection required curation of all elements so that the final collection came together as a professional and cohesive, quality, retail- ready product. This could only be created by experienced practitioners. Research significance The Akin Collection is the first Australian fashion brand to be created as a collaboration between five equally recognised Indigenous artists and five emerging fashion designers. It has familiarized the Indigenous artists to the logistics and culture of the fashion industry and the emerging fashion designers have been familiarized to the logistics and culture of how to collaborate with the unique Indigenous artwork that exists in Australia. After only three months, this culminated in a fashion parade showcasing the Akin collection to over 400 members of the public, government, media and retail. Feedback has been strong from the media and the industry, and a lookbook and photoshoot has been organised to promote and sell the collection both nationally and internationally. These concepts plus the curation outlined, has created a successful, luxury, quality collection ready for the international runways. This project has devised an ethical template for other Indigenous artists and emerging designers to create fashion collections that offer a unique aesthetic that could position and brand Australian fashion in the international marketplace. Key Words Indigenous artists, emerging fashion designers, Australian fashion design, ethical fashion, luxury Australian brand

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Ghrelin, the endogenous ligand for the GH secretagogue receptor (GHSR), is a peptide hormone with diverse physiological roles. Ghrelin regulates GH release, appetite and feeding, gut motility, and energy balance and also has roles in the cardiovascular, immune, and reproductive systems. Ghrelin and the GHSR are expressed in a wide range of normal and tumor tissues, and a fluorescein-labeled, truncated form of ghrelin is showing promise as a biomarker for prostate cancer. Plasma ghrelin levels are generally inversely related to body mass index and are unlikely to be useful as a biomarker for cancer, but may be useful as a marker for cancer cachexia. Some single nucleotide polymorphisms in the ghrelin and GHSR genes have shown associations with cancer risk; however, larger studies are required. Ghrelin regulates processes associated with cancer, including cell proliferation, apoptosis, cell migration, cell invasion, inflammation, and angiogenesis; however, the role of ghrelin in cancer is currently unclear. Ghrelin has predominantly antiinflammatory effects and may play a role in protecting against cancer-related inflammation. Ghrelin and its analogs show promise as treatments for cancer-related cachexia. Further studies using in vivo models are required to determine whether ghrelin has a role in cancer progression.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Risk factors for repeat drink driving, an important road safety issue, are well known, but estimates of Australian recidivism rates by risk factors, apart from a recent NSW study, are not. Driving records of a cohort of Queensland drink drivers matched by age, region, BAC level and prior offence to participants in a drink driving rehabilitation program were used to estimate sex-specific two- and five-year re-offence rates overall and by these factors. Estimates of the proportion of Queensland drink drivers with a prior DD offence in 2004 were used to standardise rates to the Queensland drink driving population. Rates were higher in remote areas, as were rates in males, young drivers, drivers with high BAC levels and in drivers with one and especially with at least two prior DD convictions. Five-year rates for Queensland were estimated as 21.8% in males and 16.4% in females, appreciably higher than in NSW.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The androgen receptor (AR) signaling pathway is a common therapeutic target for prostate cancer, because it is critical for the survival of both hormone-responsive and castrate-resistant tumor cells. Most of the detailed understanding that we have of AR transcriptional activation has been gained by studying classical target genes. For more than two decades, Kallikrein 3 (KLK3) (prostate-specific antigen) has been used as a prototypical AR target gene, because it is highly androgen responsive in prostate cancer cells. Three regions upstream of the KLK3 gene, including the distal enhancer, are known to contain consensus androgen-responsive elements required for AR-mediated transcriptional activation. Here, we show that KLK3 is one of a specific cluster of androgen-regulated genes at the centromeric end of the kallikrein locus with enhancers that evolved from the long terminal repeat (LTR) (LTR40a) of an endogenous retrovirus. Ligand-dependent recruitment of the AR to individual LTR-derived enhancers results in concurrent up-regulation of endogenous KLK2, KLK3, and KLKP1 expression in LNCaP prostate cancer cells. At the molecular level, a kallikrein-specific duplication within the LTR is required for maximal androgen responsiveness. Therefore, KLK3 represents a subset of target genes regulated by repetitive elements but is not typical of the whole spectrum of androgen-responsive transcripts. These data provide a novel and more detailed understanding of AR transcriptional activation and emphasize the importance of repetitive elements as functional regulatory units

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The Kallikrein (KLK) gene locus encodes a family of serine proteases and is the largest contiguous cluster of protease-encoding genes attributed an evolutionary age of 330 million years. The KLK locus has been implicated as a high susceptibility risk loci in numerous cancer studies through the last decade. The KLK3 gene already has established clinical relevance as a biomarker in prostate cancer prognosis through its encoded protein, prostate-specific antigen. Data mined through genome-wide association studies (GWAS) and next-generation sequencing point to many important candidate single nucleotide polymorphisms (SNPs) in KLK3 and other KLK genes. SNPs in the KLK locus have been found to be associated with several diseases including cancer, hypertension, cardiovascular disease and atopic dermatitis. Moreover, introducing a model incorporating SNPs to improve the efficiency of prostate-specific antigen in detecting malignant states of prostate cancer has been recently suggested. Establishing the functional relevance of these newly-discovered SNPs, and their interactions with each other, through in silico investigations followed by experimental validation, can accelerate the discovery of diagnostic and prognostic biomarkers. In this review, we discuss the various genetic association studies on the KLK loci identified either through candidate gene association studies or at the GWAS and post-GWAS front to aid researchers in streamlining their search for the most significant, relevant and therapeutically promising candidate KLK gene and/or SNP for future investigations.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Carrion-breeding Sarcophagidae (Diptera) can be used to estimate the post-mortem interval (PMI) in forensic cases. Difficulties with accurate morphological identifications at any life stage and a lack of documented thermobiological profiles have limited their current usefulness of these flies. The molecular-based approach of DNA barcoding, which utilises a 648-bp fragment of the mitochondrial cytochrome oxidase subunit I gene, was previously evaluated in a pilot study for the discrimination between 16 Australian sarcophagids. The current study comprehensively evaluated DNA barcoding on a larger taxon set of 588 adult Australian sarcophagids. A total of 39 of the 84 known Australian species were represented by 580 specimens, which includes 92% of potentially forensically important species. A further eight specimens could not be reliably identified, but included as six unidentifable taxa. A neighbour-joining phylogenetic tree was generated and nucleotide sequence divergences were calculated using the Kimura-two-parameter distance model. All species except Sarcophaga (Fergusonimyia) bancroftorum, known for high morphological variability, were resolved as reciprocally monophyletic (99.2% of cases), with most having bootstrap support of 100. Excluding S. bancroftorum, the mean intraspecific and interspecific variation ranged from 0.00-1.12% and 2.81-11.23%, respectively, allowing for species discrimination. DNA barcoding was therefore validated as a suitable method for the molecular identification of the Australian Sarcophagidae, which will aid in the implementation of this fauna in forensic entomology.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (±10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2≥0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Customer relationship marketing (CRM) initiatives are increasingly being adopted by businesses in the attempt to enhance brand loyalty and stimulate repeat purchases. The purpose of this study was to examine the extent to which destination marketing organisations (DMOs) around the world have developed a visitor relationship marketing (VRM) orientation. The proposition underpinning the study is that maintaining meaningful dialogue with previous visitors in some markets would represent a more efficient use of resources than above the line advertising to attract new visitors. Importance-performance analysis was utilised to measure destination marketers’ perceptions of the efficacy of CRM initiatives, and then rate their own organisation’s performance across the same range of initiatives. A key finding was that mean importance was higher than perceived performance for every item. While the small sample limits generalisability, in general there are appears to be a lack of strategic intent by DMOs to invest in VRM.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Small interfering RNA silences specific genes by interfering with mRNA translation, and acts to modulate or inhibit specific biological pathways; a therapy that holds great promise in the cure of many diseases. However, the naked small interfering RNA is susceptible to degradation by plasma and tissue nucleases and due to its negative charge unable to cross the cell membrane. Here we report a new polymer carrier designed to mimic the influenza virus escape mechanism from the endosome, followed by a timed release of the small interfering RNA in the cytosol through a self-catalyzed polymer degradation process. Our polymer changes to a negatively charged and non-toxic polymer after the release of small interfering RNA, presenting potential for multiple repeat doses and long-term treatment of diseases.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

A significant proportion of research in the field of human-computer interaction has been devoted to game design. Yet, a multitude of good ideas and enthusiastic game design initiatives exist, where the games never see the light of day. Unfortunately, the causes of these failures remain often unexplored and unpublished. The challenges faced by researchers and practitioners are particularly complex when designing games for special target groups, such as children, or for a serious purpose. The HCI community would benefit from a discussion on these issues in order to avoid researchers and practitioners to repeat mistakes. We want to learn from projects that started with a promising idea, but failed or faced severe challenges. This workshop will be the first at CHI focusing on 'failed game projects'. In particular, workshop participants are encouraged to discuss issues that typically received little attention in publications and hereby contribute to the discussion on failures in the design, development and evaluation of games for and or with children. As a result, the community will benefit from these insights and lessons-learned, which will enhance the design of future (serious) games with/for children.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

Granulysin is a cytolytic granule protein released by natural killer cells and activated cytotoxic T lymphocytes. The influence of exercise training on circulating granulysin concentration is unknown, as is the relationship between granulysin concentration, natural killer cell number and natural killer cell cytotoxicity. We examined changes in plasma granulysin concentration, natural killer cell number and cytotoxicity following acute exercise and different training loads. Fifteen highly trained male cyclists completed a baseline 40-km cycle time trial (TT401) followed by five weeks of normal training and a repeat time trial (TT402). The cyclists then completed four days of high intensity training followed by another time trial (TT403) on day five. Following one final week of normal training cyclists completed another time trial (TT404). Fasting venous blood was collected before and after each time trial to determine granulysin concentration, natural killer cell number and natural killer cell cytotoxicity. Granulysin concentration increased significantly after each time trial (P<0.001). Pre-exercise granulysin concentration for TT403 was significantly lower than pre-exercise concentration for TT401 (-20.3 +/- 7.5%, P<0.026), TT402 (-16.7 +/- 4.3%, P<0.003) and 7T404 (-21 +/- 4.2%, P<0.001). Circulating natural killer cell numbers also increased significantly post-exercise for each time trial (P<0.001), however there was no significant difference across TT40 (P>0.05). Exercise did not significantly alter natural killer cell cytotoxicity on a per cell basis, and there were no significant differences between the four time trials. In conclusion, plasma granulysin concentration increases following moderate duration, strenuous exercise and is decreased in response to a short-term period of intensified training.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

The double-stranded conformation of cellular DNA is a central aspect of DNA stabilisation and protection. The helix preserves the genetic code against chemical and enzymatic degradation, metabolic activation, and formation of secondary structures. However, there are various instances where single-stranded DNA is exposed, such as during replication or transcription, in the synthesis of chromosome ends, and following DNA damage. In these instances, single-stranded DNA binding proteins are essential for the sequestration and processing of single-stranded DNA. In order to bind single-stranded DNA, these proteins utilise a characteristic and evolutionary conserved single-stranded DNA-binding domain, the oligonucleotide/oligosaccharide-binding (OB)-fold. In the current review we discuss a subset of these proteins involved in the direct maintenance of genomic stability, an important cellular process in the conservation of cellular viability and prevention of malignant transformation. We discuss the central roles of single-stranded DNA binding proteins from the OB-fold domain family in DNA replication, the restart of stalled replication forks, DNA damage repair, cell cycle-checkpoint activation, and telomere maintenance.

Relevância:

10.00% 10.00%

Publicador:

Resumo:

BACKGROUND: Infection by dengue virus (DENV) is a major public health concern in hundreds of tropical and subtropical countries. French Polynesia (FP) regularly experiences epidemics that initiate, or are consecutive to, DENV circulation in other South Pacific Island Countries (SPICs). In January 2009, after a decade of serotype 1 (DENV-1) circulation, the first cases of DENV-4 infection were reported in FP. Two months later a new epidemic emerged, occurring about 20 years after the previous circulation of DENV-4 in FP. In this study, we investigated the epidemiological and molecular characteristics of the introduction, spread and genetic microevolution of DENV-4 in FP. METHODOLOGY/PRINCIPAL FINDINGS: Epidemiological data suggested that recent transmission of DENV-4 in FP started in the Leeward Islands and this serotype quickly displaced DENV-1 throughout FP. Phylogenetic analyses of the nucleotide sequences of the envelope (E) gene of 64 DENV-4 strains collected in FP in the 1980s and in 2009-2010, and some additional strains from other SPICs showed that DENV-4 strains from the SPICs were distributed into genotypes IIa and IIb. Recent FP strains were distributed into two clusters, each comprising viruses from other but distinct SPICs, suggesting that emergence of DENV-4 in FP in 2009 resulted from multiple introductions. Otherwise, we observed that almost all strains collected in the SPICs in the 1980s exhibit an amino acid (aa) substitution V287I within domain I of the E protein, and all recent South Pacific strains exhibit a T365I substitution within domain III. CONCLUSIONS/SIGNIFICANCE: This study confirmed the cyclic re-emergence and displacement of DENV serotypes in FP. Otherwise, our results showed that specific aa substitutions on the E protein were present on all DENV-4 strains circulating in SPICs. These substitutions probably acquired and subsequently conserved could reflect a founder effect to be associated with epidemiological, geographical, eco-biological and social specificities in SPICs.