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"Gould, Peter"
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Empowering communities through archaeology and heritage : the role of local governance in economic development
\"Peter G. Gould seeks to identify the essential success factors associated with a growing practice in archaeology: the sponsorship by archaeologists or heritage managers of local projects such as museums, tourism businesses, crafts cooperatives and similar activities within communities adjacent to archaeological or heritage sites. Typically, these are small projects intended to support economic advance in small communities. Rarely are they reported on in scholarly papers and, until now, they have never been subjected to study grounded in economic theory and practice. This is an area of study and analysis that is too important to lack suitable academic attention. This book argues that an essential factor in the success of community projects relates to the mechanisms used to govern the projects at the local level, and provides a much-needed systematical evaluation of the issues surrounding such governance. Drawing together theoretical insights from economics, political science, tourism scholarship, complexity scholarship, and non-profit best practices, it presents a model for community governance structures and illustrates the workings of that model through the four case studies. Armed with this book, practitioners will have both a theoretical foundation and practical approaches to consider when designing community projects\"-- Provided by publisher.
Book
Nanopore direct RNA sequencing maps the complexity of Arabidopsis mRNA processing and m6A modification
Understanding genome organization and gene regulation requires insight into RNA transcription, processing and modification. We adapted nanopore direct RNA sequencing to examine RNA from a wild-type accession of the model plant Arabidopsis thaliana and a mutant defective in mRNA methylation (m6A). Here we show that m6A can be mapped in full-length mRNAs transcriptome-wide and reveal the combinatorial diversity of cap-associated transcription start sites, splicing events, poly(A) site choice and poly(A) tail length. Loss of m6A from 3’ untranslated regions is associated with decreased relative transcript abundance and defective RNA 3′ end formation. A functional consequence of disrupted m6A is a lengthening of the circadian period. We conclude that nanopore direct RNA sequencing can reveal the complexity of mRNA processing and modification in full-length single molecule reads. These findings can refine Arabidopsis genome annotation. Further, applying this approach to less well-studied species could transform our understanding of what their genomes encode.
Journal Article
Coordinated circadian timing through the integration of local inputs in Arabidopsis thaliana
Individual plant cells have a genetic circuit, the circadian clock, that times key processes to the day-night cycle. These clocks are aligned to the day-night cycle by multiple environmental signals that vary across the plant. How does the plant integrate clock rhythms, both within and between organs, to ensure coordinated timing? To address this question, we examined the clock at the sub-tissue level across Arabidopsis thaliana seedlings under multiple environmental conditions and genetic backgrounds. Our results show that the clock runs at different speeds (periods) in each organ, which causes the clock to peak at different times across the plant in both constant environmental conditions and light-dark (LD) cycles. Closer examination reveals that spatial waves of clock gene expression propagate both within and between organs. Using a combination of modeling and experiment, we reveal that these spatial waves are the result of the period differences between organs and local coupling, rather than long-distance signaling. With further experiments we show that the endogenous period differences, and thus the spatial waves, can be generated by the organ specificity of inputs into the clock. We demonstrate this by modulating periods using light and metabolic signals, as well as with genetic perturbations. Our results reveal that plant clocks can be set locally by organ-specific inputs but coordinated globally via spatial waves of clock gene expression.
Journal Article
1p and/or 19q polysomy is an adverse prognostic factor in oligodendrogliomas, and easy to detect by automated FISH
To study the feasibility of automated analysis by FISH technique in the determination of the 1p and/or 19q polysomy in oligodendrogliomas (OGs) and to explore its prognostic value.
We analyzed a retrospective monocentric series of 145 consecutive OGs with IDH mutation and 1p/19q codeletion. For all cases, automated FISH analyses were performed to determine 1p and/or 19q polysomy status and results were compared to manual analysis to verify the concordance of the two methods. Polysomic status was then compared to clinical and histological data, the CDKN2A deletion status when available, event free survival (EFS) and overall survival (OS).
Our study comprised 79 grade 2 OGs (O2) and 66 grade 3 OGs (O3). Polysomy of 1p and/or 19q was observed in 58 cases (40% of whole cohort) with a significant enrichment in the high grade cohort (59% versus 24%; p < 0,0001) and recurrent cases (55%). A majority of polysomic cases were copolysomic for 1p and 19q (75% of the polysomic cohort) rather than 1p or 19q single polysomy (21% and 4% respectively). Polysomy was correlated to high grade histological criteria of high mitotic and Mib1 proliferative indices (p = 0,002 and p = 0,0005 respectively) and to vascular proliferation (p = 0,0003). Univariate and multivariate analysis showed a significant correlation betwen polysomy and a shorter EFS and OS (p = 0,02 and p = 0,016 respectively). Concordance between manual and automated analysis was almost perfect for both 1p and 19q analysis (96 and 98% respectively, κ = 0,92 and 0,95 respectively). Automated analysis revealed that the large majority of polysomic signatures are represented by a small number of R/G signals (mainly 7 signatures) allowing a very easy implementation to pre-existent FISH platforms analysis software.
1p and/ or 19q polysomy status represent a prognostic factor in OGs and can be easily determined by automated analysis. Our study supports the clinical interest to determine the polysomic status in all primitive or recurrent OGs and underline the benefits of automated analysis which offers a better archive storage and facilitates multicentric comparison.
Journal Article
Phosphorylation of Phosphoenolpyruvate Carboxylase Is Essential for Maximal and Sustained Dark CO2 Fixation and Core Circadian Clock Operation in the Obligate Crassulacean Acid Metabolism Species Kalanchoë fedtschenkoi
Phosphoenolpyruvate carboxylase (PPC; EC 4.1.1.31) catalyzes primary nocturnal CO2 fixation in Crassulacean acid metabolism (CAM) species. CAM PPC is regulated posttranslationally by a circadian clock-controlled protein kinase called phosphoenolpyruvate carboxylase kinase (PPCK). PPCK phosphorylates PPC during the dark period, reducing its sensitivity to feedback inhibition by malate and thus enhancing nocturnal CO2 fixation to stored malate. Here, we report the generation and characterization of transgenic RNAi lines of the obligate CAM species Kalanchoë fedtschenkoi with reduced levels of KfPPCK1 transcripts. Plants with reduced or no detectable dark phosphorylation of PPC displayed up to a 66% reduction in total dark period CO2 fixation. These perturbations paralleled reduced malate accumulation at dawn and decreased nocturnal starch turnover. Loss of oscillations in the transcript abundance of KfPPCK1 was accompanied by a loss of oscillations in the transcript abundance of many core circadian clock genes, suggesting that perturbing the only known link between CAM and the circadian clock feeds back to perturb the central circadian clock itself. This work shows that clock control of KfPPCK1 prolongs the activity of PPC throughout the dark period in K. fedtschenkoi, optimizing CAM-associated dark CO2 fixation, malate accumulation, CAM productivity, and core circadian clock robustness.
Journal Article
Longitudinal molecular trajectories of diffuse glioma in adults
The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear
1
,
2
. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.
The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure
Journal Article
Mapping the acquisition of the number word sequence in the first year of school
Learning to count and to produce the correct sequence of number words in English is not a simple process. In NSW government schools taking part in Early Action for Success, over 800 students in each of the first 3 years of school were assessed every 5 weeks over the school year to determine the highest correct oral count they could produce. Rather than displaying a steady increase in the accurate sequence of the number words produced, the kindergarten data reported here identified clear, substantial hurdles in the acquisition of the counting sequence. The large-scale, longitudinal data also provided evidence of learning to count through the teens being facilitated by the semi-regular structure of the number words in English. Instead of occurring as hurdles to starting the next counting sequence, number words corresponding to some multiples of ten (10, 20 and 100) acted as if they were rest points. These rest points appear to be artefacts of how the counting sequence is acquired. [Author abstract]
Journal Article
Shedding a new light on Huntington’s disease: how blood can both propagate and ameliorate disease pathology
Huntington’s disease (HD) is a monogenic neurodegenerative disorder resulting from a mutation in the huntingtin gene. This leads to the expression of the mutant huntingtin protein (mHTT) which provokes pathological changes in both the central nervous system (CNS) and periphery. Accumulating evidence suggests that mHTT can spread between cells of the CNS but here, we explored the possibility that mHTT could also propagate and cause pathology via the bloodstream. For this, we used a parabiosis approach to join the circulatory systems of wild-type (WT) and zQ175 mice. After surgery, we observed mHTT in the plasma and circulating blood cells of WT mice and post-mortem analyses revealed the presence of mHTT aggregates in several organs including the liver, kidney, muscle and brain. The presence of mHTT in the brain was accompanied by vascular abnormalities, such as a reduction of Collagen IV signal intensity and altered vessel diameter in the striatum, and changes in expression of Glutamic acid decarboxylase 65/67 (GAD65-67) in the cortex. Conversely, we measured reduced pathology in zQ175 mice by decreased mitochondrial impairments in peripheral organs, restored vessel diameter in the cortex and improved expression of Dopamine- and cAMP-regulated phosphoprotein 32 (DARPP32) in striatal neurons. Collectively, these results demonstrate that circulating mHTT can disseminate disease, but importantly, that healthy blood can dilute pathology. These findings have significant implications for the development of therapies in HD.
Journal Article
Tradeoffs between chilling and forcing in satisfying dormancy requirements for Pacific Northwest tree species
Many temperate and boreal tree species have a chilling requirement, that is, they need to experience cold temperatures during fall and winter to burst bud normally in the spring. Results from trials with 11 Pacific Northwest tree species are consistent with the concept that plants can accumulate both chilling and forcing units simultaneously during the dormant season and they exhibit a tradeoff between amount of forcing and chilling. That is, the parallel model of chilling and forcing was effective in predicting budburst and well chilled plants require less forcing for bud burst than plants which have received less chilling. Genotypes differed in the shape of the possibility line which describes the quantitative tradeoff between chilling and forcing units. Plants which have an obligate chilling requirement (Douglas-fir, western hemlock, western larch, pines, and true firs) and received no or very low levels of chilling did not burst bud normally even with long photoperiods. Pacific madrone and western redcedar benefited from chilling in terms of requiring less forcing to promote bud burst but many plants burst bud normally without chilling. Equations predicting budburst were developed for each species in our trials for a portion of western North America under current climatic conditions and for 2080. Mean winter temperature was predicted to increase 3.2-5.5°C and this change resulted in earlier predicted budburst for Douglas-fir throughout much of our study area (up to 74 days earlier) but later budburst in some southern portions of its current range (up to 48 days later) as insufficient chilling is predicted to occur. Other species all had earlier predicted dates of budburst by 2080 than currently. Recent warming trends have resulted in earlier budburst for some woody plant species; however, the substantial winter warming predicted by some climate models will reduce future chilling in some locations such that budburst will not consistently occur earlier.
Journal Article