193 resultados para Ligand-derived Peptides
Resumo:
In this paper, we argue that second language (L2) reading research, which has been informed by studies involving first language (L1) alphabetic English reading, may be less relevant to L2 readers with non-alphabetic reading backgrounds, such as Chinese readers with an L1 logographic (Chinese character) learning history. We provide both neuroanatomical and behavioural evidence from Chinese language reading studies to support our claims. The paper concludes with an argument outlining the need for a universal L2 reading model which can adequately account for readers with diverse L1 orthographic language learning histories.
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The regulatory pathways involved in maintaining the pluripotency of embryonic stem cells are partially known, whereas the regulatory pathways governing adult stem cells and their "stem-ness" are characterized to an even lesser extent. We, therefore, screened the transcriptome profiles of 20 osteogenically induced adult human adipose-derived stem cell (ADSC) populations and investigated for putative transcription factors that could regulate the osteogenic differentiation of these ADSC. We studied a subgroup of donors' samples that had a disparate osteogenic response transcriptome from that of induced human fetal osteoblasts and the rest of the induced human ADSC samples. From our statistical analysis, we found activating transcription factor 5 (ATF5) to be significantly and consistently down-regulated in a randomized time-course study of osteogenically differentiated adipose-derived stem cells from human donor samples. Knockdown of ATF5 with siRNA showed an increased sensitivity to osteogenic induction. This evidence suggests a role for ATF5 in the regulation of osteogenic differentiation in adipose-derived stem cells. To our knowledge, this is the first report that indicates a novel role of transcription factors in regulating osteogenic differentiation in adult or tissue specific stem cells. © 2012 Wiley Periodicals, Inc.
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ZnO nanoparticles with highly controllable particle sizes(less than 10 nm) were synthesized using organic capping ligands in Zn(Ac)2 ethanolic solution. The molecular structure of the ligands was found to have significant influence on the particle size. The multi-functional molecule tris(hydroxymethyl)-aminomethane (THMA) favoured smaller particle distributions compared with ligands possessing long hydrocarbon chains that are more frequently employed. The adsorption of capping ligands on ZnnOn crystal nuclei (where n = 4 or 18 molecular clusters of(0001) ZnO surfaces) was modelled by ab initio methods at the density functional theory (DFT) level. For the molecules examined, chemisorption proceeded via the formation of Zn...O, Zn...N, or Zn...S chemical bonds between the ligands and active Zn2+ sites on ZnO surfaces. The DFT results indicated that THMA binds more strongly to the ZnO surface than other ligands, suggesting that this molecule is very effective at stabilizing ZnO nanoparticle surfaces. This study, therefore, provides new insight into the correlation between the molecular structure of capping ligands and the morphology of metal oxide nanostructures formed in their presence.
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The study of biologically active peptides is critical to the understanding of physiological pathways, especially those involved in the development of disease. Historically, the measurement of biologically active endogenous peptides has been undertaken by radioimmunoassay, a highly sensitive and robust technique that permits the detection of physiological concentrations in different biofluid and tissue extracts. Over recent years, a range of mass spectrometric approaches have been applied to peptide quantification with limited degrees of success. Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) belong to the NPY family exhibiting regulatory effects on appetite and feeding behavior. The physiological significance of these peptides depends on their molecular forms and in vivo concentrations systemically and at local sites within tissues. In this report, we describe an approach for quantification of individual peptides within mixtures using high-performance liquid chromatography electrospray ionization tandem mass spectrometry analysis of the NPY family peptides. Aspects of quantification including sample preparation, the use of matrix-matched calibration curves, and internal standards will be discussed. This method for the simultaneous determination of NPY, PYY, and PP was accurate and reproducible but lacks the sensitivity required for measurement of their endogenous concentration in plasma. The advantages of mass spectrometric quantification will be discussed alongside the current obstacles and challenges. © 2012 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 357–366, 2012.
Resumo:
Enterococci are versatile Gram-positive bacteria that can survive under extreme conditions. Most enterococci are non-virulent and found in the gastrointestinal tract of humans and animals. Other strains are opportunistic pathogens that contribute to a large number of nosocomial infections globally. Epidemiological studies demonstrated a direct relationship between the density of enterococci in surface waters and the risk of swimmer-associated gastroenteritis. The distribution of infectious enterococcal strains from the hospital environment or other sources to environmental water bodies through sewage discharge or other means, could increase the prevalence of these strains in the human population. Environmental water quality studies may benefit from focusing on a subset of Enterococcus spp. that are consistently associated with sources of faecal pollution such as domestic sewage, rather than testing for the entire genus. E. faecalis and E. faecium are potentially good focal species for such studies, as they have been consistently identified as the dominant Enterococcus spp. in human faeces and sewage. On the other hand enterococcal infections are predominantly caused by E. faecalis and E. faecium. The characterisation of E. faecalis and E. faecium is important in studying their population structures, particularly in environmental samples. In developing and implementing rapid, robust molecular genotyping techniques, it is possible to more accurately establish the relationship between human and environmental enterococci. Of particular importance, is to determine the distribution of high risk enterococcal clonal complexes, such as E. faecium clonal complex 17 and E. faecalis clonal complexes 2 and 9 in recreational waters. These clonal complexes are recognized as particularly pathogenic enterococcal genotypes that cause severe disease in humans globally. The Pimpama-Coomera watershed is located in South East Queensland, Australia and was investigated in this study mainly because it is used intensively for agriculture and recreational purposes and has a strong anthropogenic impact. The primary aim of this study was to develop novel, universally applicable, robust, rapid and cost effective genotyping methods which are likely to yield more definitive results for the routine monitoring of E. faecalis and E. faecium, particularly in environmental water sources. To fullfill this aim, new genotyping methods were developed based on the interrogation of highly informative single nucleotide polymorphisms (SNPs) located in housekeeping genes of both E. faecalis and E. faecium. SNP genotyping was successfully applied in field investigations of the Coomera watershed, South-East Queensland, Australia. E. faecalis and E. faecium isolates were grouped into 29 and 23 SNP profiles respectively. This study showed the high longitudinal diversity of E. faecalis and E. faecium over a period of two years, and both human-related and human-specific SNP profiles were identified. Furthermore, 4.25% of E. faecium strains isolated from water was found to correspond to the important clonal complex-17 (CC17). Strains that belong to CC17 cause the majority of hospital outbreaks and clinical infections globally. Of the six sampling sites of the Coomera River, Paradise Point had the highest number of human-related and human-specific E. faecalis and E. faecium SNP profiles. The secondary aim of this study was to determine the antibiotic-resistance profiles and virulence traits associated with environmental E. faecalis and E. faecium isolates compared to human pathogenic E. faecalis and E. faecium isolates. This was performed to predict the potential health risks associated with coming into contact with these strains in the Coomera watershed. In general, clinical isolates were found to be more resistant to all the antibiotics tested compared to water isolates and they harbored more virulence traits. Multi-drug resistance was more prevalent in clinical isolates (71.18% of E. faecalis and 70.3 % of E. faecium) compared to water isolates (only 5.66 % E. faecium). However, tetracycline, gentamicin, ciprofloxacin and ampicillin resistance was observed in water isolates. The virulence gene esp was the most prevalent virulence determinant observed in clinical isolates (67.79% of E. faecalis and 70.37 % of E. faecium), and this gene has been described as a human-specific marker used for microbial source tracking (MST). The presence of esp in water isolates (16.36% of E. faecalis and 19.14% of E. faecium) could be indicative of human faecal contamination in these waterways. Finally, in order to compare overall gene expression between environmental and clinical strains of E. faecalis, a comparative gene hybridization study was performed. The results of this investigation clearly demonstrated the up-regulation of genes associated with pathogenicity in E. faecalis isolated from water. The expression study was performed at physiological temperatures relative to ambient temperatures. The up-regulation of virulence genes demonstrates that environmental strains of E. faecalis can pose an increased health risk which can lead to serious disease, particularly if these strains belong to the virulent CC17 group. The genotyping techniques developed in this study not only provide a rapid, robust and highly discriminatory tool to characterize E. faecalis and E. faecium, but also enables the efficient identification of virulent enterococci that are distributed in environmental water sources.
Resumo:
Digital information that is place- and time-specific, is increasingly becoming available on all aspects of the urban landscape. People (cf. the Social Web), places (cf. the Geo Web), and physical objects (cf. ubiquitous computing, the Internet of Things) are increasingly infused with sensors, actuators, and tagged with a wealth of digital information. Urban informatics research explores these emerging digital layers of the city at the intersection of people, place and technology. However, little is known about the challenges and new opportunities that these digital layers may offer to road users driving through today’s mega cities. We argue that this aspect is worth exploring in particular with regards to Auto-UI’s overarching goal of making cars both safer and more enjoyable. This paper presents the findings of a pilot study, which included 14 urban informatics research experts participating in a guided ideation (idea creation) workshop within a simulated environment. They were immersed into different driving scenarios to imagine novel urban informatics type of applications specific to the driving context.
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Australian higher education institutions (HEIs) have entered a new phase of regulation and accreditation which includes performance-based funding relating to the participation and retention of students from social and cultural groups previously underrepresented in higher education. However, in addressing these priorities, it is critical that HEIs do not further disadvantage students from certain groups by identifying them for attention because of their social or cultural backgrounds, circumstances which are largely beyond the control of students. In response, many HEIs are focusing effort on university-wide approaches to enhancing the student experience because such approaches will enhance the engagement, success and retention of all students, and in doing so, particularly benefit those students who come from underrepresented groups. Measuring and benchmarking student experiences and engagement that arise from these efforts is well supported by extensive collections of student experience survey data. However no comparable instrument exists that measures the capability of institutions to influence and/or enhance student experiences where capability is an indication of how well an organisational process does what it is designed to do (Rosemann & de Bruin, 2005). We have proposed that the concept of a maturity model (Marshall, 2010; Paulk, 1999) may be useful as a way of assessing the capability of HEIs to provide and implement student engagement, success and retention activities and we are currently articulating a Student Engagement, Success and Retention Maturity Model (SESR-MM), (Clarke, Nelson & Stoodley, 2012; Nelson, Clarke & Stoodley, 2012). Our research aims to address the current gap by facilitating the development of an SESR-MM instrument that aims (i) to enable institutions to assess the capability of their current student engagement and retention programs and strategies to influence and respond to student experiences within the institution; and (ii) to provide institutions with the opportunity to understand various practices across the sector with a view to further improving programs and practices relevant to their context. Our research extends the generational approach which has been useful in considering the evolutionary nature of the first year experience (FYE) (Wilson, 2009). Three generations have been identified and explored: First generation approaches that focus on co-curricular strategies (e.g. orientation and peer programs); Second generation approaches that focus on curriculum (e.g. pedagogy, curriculum design, and learning and teaching practice); and third generation approaches—also referred to as transition pedagogy—that focus on the production of an institution-wide integrated holistic intentional blend of curricular and co-curricular activities (Kift, Nelson & Clarke, 2010). Our research also moves beyond assessments of students’ experiences to focus on assessing institutional processes and their capability to influence student engagement. In essence, we propose to develop and use the maturity model concept to produce an instrument that will indicate the capability of HEIs to manage and improve student engagement, success and retention programs and strategies. The issues explored in this workshop are (i) whether the maturity model concept can be usefully applied to provide a measure of institutional capability for SESR; (ii) whether the SESR-MM can be used to assess the maturity of a particular set of institutional practices; and (iii) whether a collective assessment of an institution’s SESR capabilities can provide an indication of the maturity of the institution’s SESR activities. The workshop will be approached in three stages. Firstly, participants will be introduced to the key characteristics of maturity models, followed by a discussion of the SESR-MM and the processes involved in its development. Secondly, participants will be provided with resources to facilitate the development of a maturity model and an assessment instrument for a range of institutional processes and related practices. In the final stage of the workshop, participants will “assess” the capability of these practices to provide a collective assessment of the maturity of these processes. References Australian Council for Educational Research. (n.d.). Australasian Survey of Student Engagement. Retrieved from http://www.acer.edu.au/research/ausse/background Clarke, J., Nelson, K., & Stoodley, I. (2012, July). The Maturity Model concept as framework for assessing the capability of higher education institutions to address student engagement, success and retention: New horizon or false dawn? A Nuts & Bolts presentation at the 15th International Conference on the First Year in Higher Education, “New Horizons,” Brisbane, Australia. Department of Education, Employment and Workplace Relations. (n.d.). The University Experience Survey. Advancing quality in higher education information sheet. Retrieved from http://www.deewr.gov.au/HigherEducation/Policy/Documents/University_Experience_Survey.pdf Kift, S., Nelson, K., & Clarke, J. (2010) Transition pedagogy - a third generation approach to FYE: A case study of policy and practice for the higher education sector. The International Journal of the First Year in Higher Education, 1(1), pp. 1-20. Marshall, S. (2010). A quality framework for continuous improvement of e-Learning: The e-Learning Maturity Model. Journal of Distance Education, 24(1), 143-166. Nelson, K., Clarke, J., & Stoodley, I. (2012). An exploration of the Maturity Model concept as a vehicle for higher education institutions to assess their capability to address student engagement. A work in progress. Submitted for publication. Paulk, M. (1999). Using the Software CMM with good judgment, ASQ Software Quality Professional, 1(3), 19-29. Wilson, K. (2009, June–July). The impact of institutional, programmatic and personal interventions on an effective and sustainable first-year student experience. Keynote address presented at the 12th Pacific Rim First Year in Higher Education Conference, “Preparing for Tomorrow Today: The First Year as Foundation,” Townsville, Australia. Retrieved from http://www.fyhe.com.au/past_papers/papers09/ppts/Keithia_Wilson_paper.pdf
Resumo:
Overexpression of the receptor tyrosine kinase EphB4 is common in epithelial cancers and linked to tumor progression by promoting angiogenesis, increasing survival and facilitating invasion and migration. However, other studies have reported loss of EphB4 suggesting a tumor suppressor function in some cancers. These opposing roles may be regulated by (i) the presence of the primary ligand ephrin-B2 that regulates pathways involved in tumor suppression or (ii) the absence of ephrin-B2 that allows EphB4 signaling via ligand-independent pathways that contribute to tumor promotion. To explore this theory, EphB4 was overexpressed in the prostate cancer cell line 22Rv1 and the mammary epithelial cell line MCF-10A. Overexpressed EphB4 localized to lipid-rich regions of the plasma membrane and confirmed to be ligand-responsive as demonstrated by increased phosphorylation of ERK1/2 and internalization. EphB4 overexpressing cells demonstrated enhanced anchorage-independent growth, migration and invasion, all characteristics associated with an aggressive phenotype, and therefore supporting the hypothesis that overexpressed EphB4 facilitates tumor promotion. Importantly, these effects were reversed in the presence of ephrin-B2 which led to a reduction in EphB4 protein levels, demonstrating that ligand-dependent signaling is tumor suppressive. Furthermore, extended ligand stimulation caused a significant decrease in proliferation that correlated with a rise in caspase-3/7 and -8 activities. Together, these results demonstrate that overexpression of EphB4 confers a transformed phenotype in the case of MCF-10A cells and an increased metastatic phenotype in the case of 22Rv1 cancer cells and that both phenotypes can be restrained by stimulation with ephrin-B2, in part by reducing EphB4 levels.